Clinical Trial Results:
A Phase III Randomized, Partially DoubleBlind, ActiveComparatorControlled, LottoLot Consistency Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 4, and 6 Months Concomitantly with Prevnar 13™ and RotaTeq™
Summary


EudraCT number 
201100410839 
Trial protocol 
Outside EU/EEA 
Global end of trial date 
26 Jul 2013

Results information


Results version number 
v1(current) 
This version publication date 
03 Feb 2016

First version publication date 
17 Jul 2015

Other versions 
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
V419006


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT01340937  
WHO universal trial number (UTN) 
  
Sponsors


Sponsor organisation name 
Merck Sharp and Dohme Corp., A Subsidiary of Merck & Co., Inc.


Sponsor organisation address 
2000 Galloping Hill Rd, Kenilworth, United States, 07033


Public contact 
VP, Late Stage Development, Merck Sharp and Dohme Corp., A Subsidiary of Merck & Co., Inc., 800 6726372, ClinicalTrialsDisclosure@merck.com


Scientific contact 
VP, Late Stage Development, Merck Sharp and Dohme Corp., A Subsidiary of Merck & Co., Inc., 800 6726372, ClinicalTrialsDisclosure@merck.com


Paediatric regulatory details


Is trial part of an agreed paediatric investigation plan (PIP) 
Yes


EMA paediatric investigation plan number(s) 
EMEA000394PIP0108  
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? 
Yes


Results analysis stage


Analysis stage 
Final


Date of interim/final analysis 
26 Jul 2013


Is this the analysis of the primary completion data? 
No


Global end of trial reached? 
Yes


Global end of trial date 
26 Jul 2013


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
To evaluate the consistency of the Postdose 3 immune response to three manufactured lots of PR5I when given at 2, 4, and 6 months of age with respect to geometric mean concentrations (GMCs) and geometric mean titers (GMTs).


Protection of trial subjects 
Only subjects that met all the study inclusion and none of the exclusion criteria were randomized and vaccinated in the study. Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment was also available on site in case of any immediate allergic reactions.


Background therapy 
Not applicable  
Evidence for comparator 
Not applicable  
Actual start date of recruitment 
11 May 2011


Long term followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
No


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
United States: 2808


Worldwide total number of subjects 
2808


EEA total number of subjects 
0


Number of subjects enrolled per age group 

In utero 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
2808


Children (211 years) 
0


Adolescents (1217 years) 
0


Adults (1864 years) 
0


From 65 to 84 years 
0


85 years and over 
0



Recruitment


Recruitment details 
Study subjects were enrolled from 11 May 2011 to 26 July 2013 at 73 clinical sites in the United States.  
Preassignment


Screening details 
A total of 2808 subjects met all of the inclusion criteria and were enrolled and randomized. Infant vaccinations were administered at 2, 4, and 6 months and the toddler vaccinations at 15 months of age. The Interim Period is the time between the last vaccination of the infant series and the time of administration of the toddler vaccination.  
Period 1


Period 1 title 
Infant Series


Is this the baseline period? 
Yes  
Allocation method 
Randomised  controlled


Blinding used 
Double blind  
Roles blinded 
Assessor, Subject, Investigator, Monitor  
Blinding implementation details 
This was a partially doubleblind study (Investigator, study personnel, subject's parent(s), and personnel of the Sponsor) were blinded to the Lot A, B, or C of V419 the subject was randomized to receive but they were not blinded to the subject's vaccination group (V419 or Control).


Arms


Are arms mutually exclusive 
Yes


Arm title

V419 Lot A  
Arm description 
V419 (Lot A) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Arm type 
Experimental  
Investigational medicinal product name 
PR5I


Investigational medicinal product code 
V419


Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.


Investigational medicinal product name 
PENTACEL™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection at 15 months of age.


Investigational medicinal product name 
RotaTeq™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Oral solution


Routes of administration 
Oral use


Dosage and administration details 
2 mL, oral, 1 dose each at 2, 4, and 6 months of age.


Investigational medicinal product name 
Prevnar13™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Arm title

V419 Lot B  
Arm description 
V419 (Lot B) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Arm type 
Experimental  
Investigational medicinal product name 
PR5I


Investigational medicinal product code 
V419


Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.


Investigational medicinal product name 
PENTACEL™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection at 15 months of age.


Investigational medicinal product name 
RotaTeq™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Oral solution


Routes of administration 
Oral use


Dosage and administration details 
2 mL, oral, 1 dose each at 2, 4, and 6 months of age.


Investigational medicinal product name 
Prevnar13™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Arm title

V419 Lot C  
Arm description 
V419 (Lot C) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Arm type 
Experimental  
Investigational medicinal product name 
PR5I


Investigational medicinal product code 
V419


Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.


Investigational medicinal product name 
PENTACEL™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection at 15 months of age.


Investigational medicinal product name 
RotaTeq™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Oral solution


Routes of administration 
Oral use


Dosage and administration details 
2 mL, oral, 1 dose each at 2, 4, and 6 months of age.


Investigational medicinal product name 
Prevnar13™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Arm title

Control  
Arm description 
PENTACEL™ 0.5 mL IM at 2, 4, 6, and 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age; and RECOMBIVAX HB™ 0.5 mL IM at 2 and 6 months of age.  
Arm type 
Active comparator  
Investigational medicinal product name 
PENTACEL™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Investigational medicinal product name 
RotaTeq™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Oral solution


Routes of administration 
Oral use


Dosage and administration details 
2 mL, oral, 1 dose each at 2, 4, and 6 months of age.


Investigational medicinal product name 
Prevnar13™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Investigational medicinal product name 
RECOMBIVAX HB™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2 and 6 months of age.




Period 2


Period 2 title 
Interim Period


Is this the baseline period? 
No  
Allocation method 
Randomised  controlled


Blinding used 
Double blind  
Roles blinded 
Assessor, Subject, Investigator, Data analyst  
Blinding implementation details 
This was a partially doubleblind study (Investigator, study personnel, subject's parent(s), and personnel of the Sponsor) were blinded to the Lot A, B, or C of V419 the subject was randomized to receive but they were not blinded to the subject's vaccination group (V419 or Control).


Arms


Are arms mutually exclusive 
Yes


Arm title

V419 Lot A  
Arm description 
V419 (Lot A) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Arm type 
Experimental  
Investigational medicinal product name 
PR5I


Investigational medicinal product code 
V419


Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.


Investigational medicinal product name 
PENTACEL™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection at 15 months of age.


Investigational medicinal product name 
RotaTeq™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Oral solution


Routes of administration 
Oral use


Dosage and administration details 
2 mL, oral, 1 dose each at 2, 4, and 6 months of age.


Investigational medicinal product name 
Prevnar13™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Arm title

V419 Lot B  
Arm description 
V419 (Lot B) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Arm type 
Experimental  
Investigational medicinal product name 
PR5I


Investigational medicinal product code 
V419


Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.


Investigational medicinal product name 
Prevnar13™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Investigational medicinal product name 
RotaTeq™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Oral solution


Routes of administration 
Oral use


Dosage and administration details 
2 mL, oral, 1 dose each at 2, 4, and 6 months of age.


Investigational medicinal product name 
PENTACEL™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection at 15 months of age.


Arm title

V419 Lot C  
Arm description 
V419 (Lot C) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Arm type 
Experimental  
Investigational medicinal product name 
PR5I


Investigational medicinal product code 
V419


Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.


Investigational medicinal product name 
RotaTeq™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Oral solution


Routes of administration 
Oral use


Dosage and administration details 
2 mL, oral, 1 dose each at 2, 4, and 6 months of age.


Investigational medicinal product name 
Prevnar13™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Investigational medicinal product name 
PENTACEL™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection at 15 months of age.


Arm title

Control  
Arm description 
PENTACEL™ 0.5 mL IM at 2, 4, 6, and 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age; and RECOMBIVAX HB™ 0.5 mL IM at 2 and 6 months of age.  
Arm type 
Active comparator  
Investigational medicinal product name 
PENTACEL™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Investigational medicinal product name 
Prevnar13™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Investigational medicinal product name 
RECOMBIVAX HB™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2 and 6 months of age.


Investigational medicinal product name 
RotaTeq™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Oral solution


Routes of administration 
Oral use


Dosage and administration details 
2 mL, oral, 1 dose each at 2, 4, and 6 months of age.




Period 3


Period 3 title 
Toddler Vaccinations


Is this the baseline period? 
No  
Allocation method 
Randomised  controlled


Blinding used 
Double blind  
Roles blinded 
Assessor, Subject, Investigator, Data analyst  
Blinding implementation details 
This was a partially doubleblind study (Investigator, study personnel, subject's parent(s), and personnel of the Sponsor) were blinded to the Lot A, B, or C of V419 the subject was randomized to receive but they were not blinded to the subject's vaccination group (V419 or Control).


Arms


Are arms mutually exclusive 
Yes


Arm title

V419 Lot A  
Arm description 
V419 (Lot A) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Arm type 
Experimental  
Investigational medicinal product name 
PR5I


Investigational medicinal product code 
V419


Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.


Investigational medicinal product name 
PENTACEL™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection at 15 months of age.


Investigational medicinal product name 
RotaTeq™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Oral solution


Routes of administration 
Oral use


Dosage and administration details 
2 mL, oral, 1 dose each at 2, 4, and 6 months of age.


Investigational medicinal product name 
Prevnar13™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Arm title

V419 Lot B  
Arm description 
V419 (Lot B) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Arm type 
Experimental  
Investigational medicinal product name 
PR5I


Investigational medicinal product code 
V419


Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.


Investigational medicinal product name 
Prevnar13™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Investigational medicinal product name 
RotaTeq™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Oral solution


Routes of administration 
Oral use


Dosage and administration details 
2 mL, oral, 1 dose each at 2, 4, and 6 months of age.


Investigational medicinal product name 
PENTACEL™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection at 15 months of age.


Arm title

V419 Lot C  
Arm description 
V419 (Lot C) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Arm type 
Experimental  
Investigational medicinal product name 
PR5I


Investigational medicinal product code 
V419


Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.


Investigational medicinal product name 
RotaTeq™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Oral solution


Routes of administration 
Oral use


Dosage and administration details 
2 mL, oral, 1 dose each at 2, 4, and 6 months of age.


Investigational medicinal product name 
Prevnar13™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Investigational medicinal product name 
PENTACEL™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection at 15 months of age.


Arm title

Control  
Arm description 
PENTACEL™ 0.5 mL IM at 2, 4, 6, and 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age; and RECOMBIVAX HB™ 0.5 mL IM at 2 and 6 months of age.  
Arm type 
Active comparator  
Investigational medicinal product name 
PENTACEL™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Investigational medicinal product name 
RotaTeq™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Oral solution


Routes of administration 
Oral use


Dosage and administration details 
2 mL, oral, 1 dose each at 2, 4, and 6 months of age.


Investigational medicinal product name 
Prevnar13™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Investigational medicinal product name 
RECOMBIVAX HB™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2 and 6 months of age.




Period 4


Period 4 title 
Combined Lots


Is this the baseline period? 
No  
Allocation method 
Randomised  controlled


Blinding used 
Double blind  
Roles blinded 
Assessor, Subject, Investigator, Data analyst  
Blinding implementation details 
Following lot consistency evaluation, data of subjects that received the individual vaccine lots were pooled for safety evaluation compared to the control group.


Arms


Are arms mutually exclusive 
No


Arm title

Combined Lot A, B, and C  
Arm description 
V419 (Combined Lots A, B, and C) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; Pentacel™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age. Following lot consistency evaluation, data of subjects that received the individual vaccine lots were pooled for safety evaluation compared to the control group.  
Arm type 
Experimental  
Investigational medicinal product name 
PR5I


Investigational medicinal product code 
V419


Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.


Investigational medicinal product name 
Prevnar13™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Investigational medicinal product name 
RotaTeq™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Oral solution


Routes of administration 
Oral use


Dosage and administration details 
2 mL, oral, 1 dose each at 2, 4, and 6 months of age.


Investigational medicinal product name 
PENTACEL™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection at 15 months of age.


Arm title

Control  
Arm description 
PENTACEL™ 0.5 mL IM at 2, 4, 6, and 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age; and RECOMBIVAX HB™ 0.5 mL IM at 2 and 6 months of age.  
Arm type 
Active comparator  
Investigational medicinal product name 
PENTACEL™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Investigational medicinal product name 
RECOMBIVAX HB™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2 and 6 months of age.


Investigational medicinal product name 
Prevnar13™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Suspension for injection


Routes of administration 
Intramuscular use


Dosage and administration details 
0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.


Investigational medicinal product name 
RotaTeq™


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Oral solution


Routes of administration 
Oral use


Dosage and administration details 
2 mL, oral, 1 dose each at 2, 4, and 6 months of age.





Baseline characteristics reporting groups


Reporting group title 
V419 Lot A


Reporting group description 
V419 (Lot A) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Reporting group title 
V419 Lot B


Reporting group description 
V419 (Lot B) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Reporting group title 
V419 Lot C


Reporting group description 
V419 (Lot C) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Reporting group title 
Control


Reporting group description 
PENTACEL™ 0.5 mL IM at 2, 4, 6, and 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age; and RECOMBIVAX HB™ 0.5 mL IM at 2 and 6 months of age.  



End points reporting groups


Reporting group title 
V419 Lot A


Reporting group description 
V419 (Lot A) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Reporting group title 
V419 Lot B


Reporting group description 
V419 (Lot B) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Reporting group title 
V419 Lot C


Reporting group description 
V419 (Lot C) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Reporting group title 
Control


Reporting group description 
PENTACEL™ 0.5 mL IM at 2, 4, 6, and 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age; and RECOMBIVAX HB™ 0.5 mL IM at 2 and 6 months of age.  
Reporting group title 
V419 Lot A


Reporting group description 
V419 (Lot A) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Reporting group title 
V419 Lot B


Reporting group description 
V419 (Lot B) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Reporting group title 
V419 Lot C


Reporting group description 
V419 (Lot C) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Reporting group title 
Control


Reporting group description 
PENTACEL™ 0.5 mL IM at 2, 4, 6, and 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age; and RECOMBIVAX HB™ 0.5 mL IM at 2 and 6 months of age.  
Reporting group title 
V419 Lot A


Reporting group description 
V419 (Lot A) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Reporting group title 
V419 Lot B


Reporting group description 
V419 (Lot B) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Reporting group title 
V419 Lot C


Reporting group description 
V419 (Lot C) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; PENTACEL™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Reporting group title 
Control


Reporting group description 
PENTACEL™ 0.5 mL IM at 2, 4, 6, and 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age; and RECOMBIVAX HB™ 0.5 mL IM at 2 and 6 months of age.  
Reporting group title 
Combined Lot A, B, and C


Reporting group description 
V419 (Combined Lots A, B, and C) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; Pentacel™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age. Following lot consistency evaluation, data of subjects that received the individual vaccine lots were pooled for safety evaluation compared to the control group.  
Reporting group title 
Control


Reporting group description 
PENTACEL™ 0.5 mL IM at 2, 4, 6, and 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age; and RECOMBIVAX HB™ 0.5 mL IM at 2 and 6 months of age. 


End point title 
Geometric Mean Concentrations (GMC) for Antibodies to Polyribosylribitol Phosphate (PRP) Antigen  
End point description 
Subject serum samples were collected for testing with a radioimmunoassay for antibodies to Haemophilus influenza type b capsular polysaccharide polyribosylribitol phosphate (PRP). The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Primary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot A/Lot B Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot B ratio.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1200


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[1]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot B)  
Point estimate 
0.91


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.77  
upper limit 
1.08  
Notes [1]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot B/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot B/Lot C ratio.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1191


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[2]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot B/Lot C)  
Point estimate 
0.94


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.79  
upper limit 
1.12  
Notes [2]  The estimates for GMC ratio is based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot A/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot C ratio.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1199


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[3]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot C)  
Point estimate 
0.86


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.72  
upper limit 
1.02  
Notes [3]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Combined Lots A, B, and C/Control Ratio  
Statistical analysis description 
GMC ratio (Combined Lots A, B, and C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
2083


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[4]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC ratio (Combined/Control)  
Point estimate 
1.63


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.35  
upper limit 
1.98  
Notes [4]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 


End point title 
Geometric Mean Concentrations (GMC) for Antibodies to Hepatitis B Surface Antigen  
End point description 
Subject serum samples were collected for testing with an enhanced chemiluminescence assay for antibodies to Hepatitis B Surface Antigen. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Primary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot A/Lot B Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot B ratio.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1187


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[5]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot B)  
Point estimate 
0.87


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.76  
upper limit 
0.98  
Notes [5]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot A/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot C ratio.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1168


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[6]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot C)  
Point estimate 
0.85


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.74  
upper limit 
0.96  
Notes [6]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot B/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot B/Lot C ratio.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1179


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[7]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot B/Lot C)  
Point estimate 
0.98


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.86  
upper limit 
1.11  
Notes [7]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 


End point title 
Geometric Mean Concentrations (GMC) for Antibodies to Diphtheria Toxin  
End point description 
Subject serum samples were collected for testing with a micrometabolic inhibition test for neutralizing antibodies to diphtheria toxin. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Primary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot A/Lot B Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot B ratio.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1247


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[8]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot B)  
Point estimate 
0.95


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.84  
upper limit 
1.07  
Notes [8]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot A/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot C ratio.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1240


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[9]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot C)  
Point estimate 
0.97


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.86  
upper limit 
1.09  
Notes [9]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot B/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot B/Lot C ratio.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1243


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[10]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot B/Lot C)  
Point estimate 
1.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
1.14  
Notes [10]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 


End point title 
Geometric Mean Concentrations (GMC) for Antibodies to Tetanus Toxin  
End point description 
Subject serum samples were collected for testing with an enzymelinked immunosorbent assay (ELISA) for antitetanus antibodies. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Primary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot A/Lot B Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot B ratio.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1231


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[11]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot B)  
Point estimate 
0.97


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.91  
upper limit 
1.04  
Notes [11]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot A/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot C ratio.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1234


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[12]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot C)  
Point estimate 
1.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.95  
upper limit 
1.09  
Notes [12]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot B/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot B/Lot C ratio.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1221


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[13]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot B/Lot C)  
Point estimate 
1.05


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.98  
upper limit 
1.13  
Notes [13]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 


End point title 
Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Toxin  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis toxin. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Primary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot A/Lot B Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot B ratio.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1281


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[14]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot B)  
Point estimate 
1.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.96  
upper limit 
1.1  
Notes [14]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot B/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot B/Lot C ratio.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1256


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[15]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot B/Lot C)  
Point estimate 
0.99


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.92  
upper limit 
1.06  
Notes [15]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot A/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot C ratio.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1269


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[16]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot C)  
Point estimate 
1.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.95  
upper limit 
1.09  
Notes [16]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Combined Lots A, B, and C/Control Ratio  
Statistical analysis description 
GMC ratio (Combined Lots A, B, and C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
2212


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[17]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC ratio (Combined Lots/Control)  
Point estimate 
1.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.11  
upper limit 
1.29  
Notes [17]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio ≥0.67. 


End point title 
Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Filamentous Hemagglutinin (FHA)  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis FHA. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Primary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot A/Lot B Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot B ratio.


Comparison groups 
V419 Lot B v V419 Lot A


Number of subjects included in analysis 
1275


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[18]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot B)  
Point estimate 
0.89


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.83  
upper limit 
0.96  
Notes [18]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot B/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot B/Lot C ratio.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1259


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[19]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot B/Lot C)  
Point estimate 
0.87


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.81  
upper limit 
0.94  
Notes [19]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot A/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot C ratio.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1272


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[20]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot C)  
Point estimate 
0.78


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.72  
upper limit 
0.83  
Notes [20]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Combined Lots A, B, and C/Control Ratio  
Statistical analysis description 
GMC ratio (Combined Lots A, B, and C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
2215


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[21]}  
Pvalue 
= 0.419  
Method 
ANCOVA  
Parameter type 
GMC ratio (Combined Lots/Control)  
Point estimate 
0.67


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.62  
upper limit 
0.73  
Notes [21]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 


End point title 
Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Pertactin  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Primary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot A/Lot B Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot B ratio.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1248


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[22]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot B)  
Point estimate 
0.97


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.87  
upper limit 
1.09  
Notes [22]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot B/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot B/Lot C ratio.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1227


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[23]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot B/Lot C)  
Point estimate 
0.96


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.85  
upper limit 
1.08  
Notes [23]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot A/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot C ratio.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1243


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[24]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot C)  
Point estimate 
0.93


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.83  
upper limit 
1.05  
Notes [24]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Combined Lots A, B, and C/Control Ratio  
Statistical analysis description 
GMC ratio (Combined Lots A, B, and C/Control)


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2162


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[25]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC ratio (Combined Lots/Control)  
Point estimate 
1.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
1.17  
Notes [25]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 


End point title 
Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Fimbriae  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Primary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot A/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot C ratio.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1264


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[26]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot C)  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.73  
upper limit 
0.87  
Notes [26]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot A/Lot B Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot A/Lot B ratio.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1273


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[27]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot A/Lot B)  
Point estimate 
0.78


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.72  
upper limit 
0.85  
Notes [27]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot B/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMC of Lot B/Lot C ratio.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1255


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[28]}  
Method 
ANCOVA  
Parameter type 
GMC ratio (Lot B/Lot C)  
Point estimate 
1.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.93  
upper limit 
1.11  
Notes [28]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMC ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Combined Lots A, B, and C/Control Ratio  
Statistical analysis description 
GMC ratio (Combined Lots A, B, and C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
2205


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[29]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC ratio (Combined Lots/Control)  
Point estimate 
1.51


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.37  
upper limit 
1.66  
Notes [29]  The estimates for GMC ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 


End point title 
Geometric Mean Titer (GMT) for Antibodies to Poliovirus Type 1  
End point description 
Subject serum samples were collected for testing with a micrometabolic inhibition test for neutralizing antibodies to poliovirus type 1. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Primary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot A/Lot B Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMT of Lot A/Lot B ratio.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1262


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[30]}  
Method 
ANCOVA  
Parameter type 
GMT ratio (Lot A/Lot B)  
Point estimate 
0.86


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.76  
upper limit 
0.96  
Notes [30]  The estimates for GMT ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMT ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot A/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMT of Lot A/Lot C ratio.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1258


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[31]}  
Method 
ANCOVA  
Parameter type 
GMT ratio (Lot A/Lot C)  
Point estimate 
0.88


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.79  
upper limit 
0.99  
Notes [31]  The estimates for GMT ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMT ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot B/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMT of Lot B/Lot C ratio.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1260


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[32]}  
Method 
ANCOVA  
Parameter type 
GMT ratio (Lot B/Lot C)  
Point estimate 
1.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.92  
upper limit 
1.15  
Notes [32]  The estimates for GMT ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMT ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 


End point title 
Geometric Mean Titer (GMT) for Antibodies to Poliovirus Type 2  
End point description 
Subject serum samples were collected for testing with a micrometabolic inhibition test for neutralizing antibodies to Poliovirus Type 2. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Primary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot A/Lot B Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMT of Lot A/Lot B ratio.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1262


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[33]}  
Method 
ANCOVA  
Parameter type 
GMT ratio (Lot A/Lot B)  
Point estimate 
0.94


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.84  
upper limit 
1.05  
Notes [33]  The estimates for GMT ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMT ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot B/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMT of Lot B/Lot C ratio.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1265


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[34]}  
Method 
ANCOVA  
Parameter type 
GMT ratio (Lot B/Lot C)  
Point estimate 
0.98


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.87  
upper limit 
1.09  
Notes [34]  The estimates for GMT ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMT ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot A/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMT of Lot A/Lot C ratio.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1263


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[35]}  
Method 
ANCOVA  
Parameter type 
GMT ratio (Lot A/Lot C)  
Point estimate 
0.91


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.82  
upper limit 
1.02  
Notes [35]  The estimates for GMT ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMT ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 


End point title 
Geometric Mean Titer (GMT) for Antibodies to Poliovirus Type 3  
End point description 
Subject serum samples were collected for testing with a micrometabolic inhibition test for neutralizing antibodies Poliovirus Type 3. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Primary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot A/Lot B Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMT of Lot A/Lot B ratio.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1249


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[36]}  
Method 
ANCOVA  
Parameter type 
GMT ratio (Lot A/Lot B)  
Point estimate 
1.06


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.92  
upper limit 
1.22  
Notes [36]  The estimates for GMT ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMT ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot B/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMT of Lot B/Lot C ratio.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1250


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[37]}  
Method 
ANCOVA  
Parameter type 
GMT ratio (Lot B/Lot C)  
Point estimate 
1.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
1.19  
Notes [37]  The estimates for GMT ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMT ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 

Statistical analysis title 
Lot A/Lot C Ratio  
Statistical analysis description 
Lot consistency analysis regarding GMT of Lot A/Lot C ratio.


Comparison groups 
V419 Lot C v V419 Lot A


Number of subjects included in analysis 
1249


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[38]}  
Method 
ANCOVA  
Parameter type 
GMT ratio (Lot A/Lot C)  
Point estimate 
1.09


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.95  
upper limit 
1.26  
Notes [38]  The estimates for GMT ratio are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the GMT ratios between any 2 lots were within the equivalence margin (0.67 to 1.5). 


End point title 
Percentage of Subjects Responding to Polyribosylribitol Phosphate (PRP) Antigen  
End point description 
Subject serum samples were collected for testing with a radioimmunoassay for antibodies to Haemophilus influenza type b capsular polysaccharide polyribosylribitol phosphate (PRP). Sera response or endpoint was defined as a titer ≥0.15 µg/mL and ≥1.0 µg/mL. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Secondary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot ALot B Difference â‰¥1 ug/mL  
Statistical analysis description 
Response rate analysis of Lot ALot B mean difference.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1200


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[39]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.31  
upper limit 
3.35  
Notes [39]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Lot ALot C Difference â‰¥1 ug/mL  
Statistical analysis description 
Response rate analysis of Lot ALot C mean difference.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1200


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[40]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
1.62


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.38  
upper limit 
2.12  
Notes [40]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Lot BLot C Difference â‰¥1 ug/mL  
Statistical analysis description 
Response rate analysis of Lot BLot C mean difference.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1192


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[41]}  
Method 

Parameter type 
Mean difference (final values)  
Point estimate 
1.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.89  
upper limit 
2.58  
Notes [41]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Combined LotsControl Difference â‰¥ 0.15 ug/mL  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2083


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[42]}  
Pvalue 
< 0.001 ^{[43]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
2.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.39  
upper limit 
5.12  
Notes [42]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥5%. [43]  Onesided pvalue 

Statistical analysis title 
Combined Lots A, B, CControl Difference â‰¥1 ug/mL  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
2083


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[44]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
7.93


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.38  
upper limit 
13.17  
Notes [44]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥10%. 


End point title 
Percentage of Subjects Responding to Hepatitis B Surface Antigen  
End point description 
Subject serum samples were collected for testing with an enhanced chemiluminescence assay for antibodies to Hepatitis B Surface Antigen. Sera response or endpoint was defined as a titer ≥ 10 mIU/mL. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Secondary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot ALot C Difference  
Statistical analysis description 
Response rate analysis of Lot ALot C mean difference.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1168


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[45]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.34


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.23  
upper limit 
0.32  
Notes [45]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Lot ALot B Difference  
Statistical analysis description 
Response rate analysis of Lot ALot B mean difference.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1187


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[46]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.34


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.23  
upper limit 
0.3  
Notes [46]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Lot BLot C Difference  
Statistical analysis description 
Response rate analysis of Lot BLot C mean difference.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1179


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[47]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.64  
upper limit 
0.66  
Notes [47]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Combined Lots A, B, CControl Difference  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
2053


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[48]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.92


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
2.9  
Notes [48]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥10%. 


End point title 
Percentage of Subjects Responding to Diphtheria Toxin  
End point description 
Subject serum samples were collected for testing with a micrometabolic inhibition test for neutralizing antibodies to diphtheria toxin. Sera response or endpoint was defined as a titer ≥ 0.1 IU/mL. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Secondary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot ALot B Difference  
Statistical analysis description 
Response rate analysis of Lot ALot B mean difference.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1247


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[49]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.74  
upper limit 
4.24  
Notes [49]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Lot BLot C Difference  
Statistical analysis description 
Response rate analysis of Lot BLot C mean difference.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1243


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[50]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
1.64


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.56  
upper limit 
2.28  
Notes [50]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Lot ALot C Difference  
Statistical analysis description 
Response rate analysis of Lot ALot C mean difference.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1240


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[51]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
1.35


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.26  
upper limit 
2.57  
Notes [51]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Combined Lots A, B, CControl Difference  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
2166


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[52]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
2.35


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.02  
upper limit 
2.09  
Notes [52]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥10%. 


End point title 
Percentage of Subjects Responding to Tetanus Toxin  
End point description 
Subject serum samples were collected for testing with an ELISA for antitetanus antibodies. Sera response or endpoint was defined as a titer ≥ 0.1 IU/mL. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Secondary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot ALot C Difference  
Statistical analysis description 
Response rate analysis of Lot ALot C mean difference.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1234


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[53]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
0.47  
Notes [53]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (5% to 5%). 

Statistical analysis title 
Lot ALot B Difference  
Statistical analysis description 
Response rate analysis of Lot ALot B mean difference.


Comparison groups 
V419 Lot B v V419 Lot A


Number of subjects included in analysis 
1231


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[54]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.91  
upper limit 
0.47  
Notes [54]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (5% to 5%). 

Statistical analysis title 
Lot BLot C Difference  
Statistical analysis description 
Response rate analysis of Lot BLot C mean difference.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1221


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[55]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.63  
upper limit 
0.62  
Notes [55]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (5% to 5%). 

Statistical analysis title 
Combined Lots A, B, CControl Difference  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2143


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[56]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
1.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.46  
upper limit 
3.33  
Notes [56]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥5%. 


End point title 
Percentage of Subjects Responding to Pertussis Toxin  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis toxin. Sera response or endpoint was defined as follows: (1) if the pre dose titer was <4 times the lower limit of quantitation (4X LLOQ) then the post dose titer was ≥4X LLOQ; (2) if the predose titer was ≥4X LLOQ then the post dose titer was ≥ the predose titer. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Secondary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot ALot B Difference  
Statistical analysis description 
Response rate analysis of Lot ALot B mean difference.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1181


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[57]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
1.73


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.37  
upper limit 
3.4  
Notes [57]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Lot ALot C Difference  
Statistical analysis description 
Response rate analysis of Lot ALot C mean difference.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1176


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[58]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.77  
upper limit 
1.63  
Notes [58]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Lot BLot C Difference  
Statistical analysis description 
Response rate analysis of Lot BLot C mean difference.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1165


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[59]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
1.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.03  
upper limit 
0.15  
Notes [59]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Combined Lots A, B, CControl Difference  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
2050


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[60]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.72


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.59  
upper limit 
3.14  
Notes [60]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥10%. 


End point title 
Percentage of Subjects Responding to Pertussis Filamentous Hemagglutinin (FHA)  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin. Sera response or endpoint was defined as follows: (1) if the pre dose titer was <4X LLOQ then the post dose titer was ≥4X LLOQ; (2) if the predose titer was ≥4X LLOQ then the post dose titer was ≥ the predose titer. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Secondary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot ALot C Difference  
Statistical analysis description 
Response rate analysis of Lot ALot C mean difference.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1221


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[61]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
3.06


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.79  
upper limit 
0.67  
Notes [61]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Lot ALot B Difference  
Statistical analysis description 
Response rate analysis of Lot ALot B mean difference.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1235


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[62]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
1.35


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.17  
upper limit 
2.47  
Notes [62]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Combined Lots A, B, CControl Difference  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, CControl mean difference.


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
2140


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[63]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
4.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.73  
upper limit 
0.86  
Notes [63]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥10%. 

Statistical analysis title 
Lot BLot C Difference  
Statistical analysis description 
Response rate analysis of Lot BLot C mean difference.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1216


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[64]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
1.71


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.37  
upper limit 
1.94  
Notes [64]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 


End point title 
Percentage of Subjects Responding to Pertussis Pertactin (PRN)  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin (PRN). Sera response or endpoint was defined as follows: (1) if the pre dose titer was <4X LLOQ then the postdose titer was ≥4X LLOQ; (2) if the predose titer was ≥4X LLOQ then the postdose titer was ≥ the predose titer. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Secondary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot ALot B Difference  
Statistical analysis description 
Response rate analysis of Lot ALot B mean difference.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1164


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[65]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
2.77


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.83  
upper limit 
7.39  
Notes [65]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Lot ALot C Difference  
Statistical analysis description 
Response rate analysis of Lot ALot C mean difference.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1150


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[66]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
2.41


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.21  
upper limit 
7.06  
Notes [66]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Lot BLot C Difference  
Statistical analysis description 
Response rate analysis of Lot BLot C mean difference.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1134


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[67]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.14  
upper limit 
4.42  
Notes [67]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Combined Lots A, B, CControl Difference  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
2010


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[68]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
3.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.7  
upper limit 
8.85  
Notes [68]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥10%. 


End point title 
Percentage of Subjects Responding to Pertussis Fimbriae  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. Sera response or endpoint was defined as follows: (1) if the pre dose titer was <4X LLOQ then the post dose titer was ≥4X LLOQ; (2) if the predose titer was ≥4X LLOQ then the post dose titer was ≥ the predose titer. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Secondary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot ALot B Difference  
Statistical analysis description 
Response rate analysis of Lot ALot B mean difference.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1224


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[69]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
4.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.69  
upper limit 
0.63  
Notes [69]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Lot ALot C Difference  
Statistical analysis description 
Response rate analysis of Lot ALot C mean difference.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1207


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[70]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
4.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.75  
upper limit 
0.66  
Notes [70]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Lot BLot C Difference  
Statistical analysis description 
Response rate analysis of Lot BLot C mean difference.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1205


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[71]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.32  
upper limit 
3.2  
Notes [71]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (10% to 10%). 

Statistical analysis title 
Combined Lots A, B, CControl Difference  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2116


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[72]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
2.85


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.85  
upper limit 
7.36  
Notes [72]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥10%. 


End point title 
Percentage of Subjects Responding to Poliovirus Type 1  
End point description 
Subject serum samples were collected for testing with a microneutralization inhibition test for neutralizing antibodies to Poliovirus Type 1. Sera response or endpoint is defined as a titer ≥8. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Secondary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot ALot B Difference  
Statistical analysis description 
Response rate analysis of Lot ALot B mean difference.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1262


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[73]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.61  
upper limit 
0.61  
Notes [73]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (5% to 5%). 

Statistical analysis title 
Lot ALot C Difference  
Statistical analysis description 
Response rate analysis of Lot ALot C mean difference.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1258


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[74]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.61  
upper limit 
0.61  
Notes [74]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (5% to 5%). 

Statistical analysis title 
Lot BLot C Difference  
Statistical analysis description 
Response rate analysis of Lot BLot C mean difference.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1260


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[75]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.61  
upper limit 
0.61  
Notes [75]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (5% to 5%). 

Statistical analysis title 
Combined Lots A, B, CControl Difference  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
2197


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[76]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.66


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.18  
upper limit 
2.36  
Notes [76]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥5%. 


End point title 
Percentage of Subjects Responding to Poliovirus Type 2  
End point description 
Subject serum samples were collected for testing with a microneutralization inhibition test for neutralizing antibodies to Poliovirus Type 2. Sera response or endpoint is defined as a titer ≥8. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Secondary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot ALot B Difference  
Statistical analysis description 
Response rate analysis of Lot ALot B mean difference.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1262


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[77]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.61  
upper limit 
0.61  
Notes [77]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (5% to 5%). 

Statistical analysis title 
Lot BLot C Difference  
Statistical analysis description 
Response rate analysis of Lot BLot C mean difference.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1265


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[78]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.61  
upper limit 
0.6  
Notes [78]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (5% to 5%). 

Statistical analysis title 
Lot ALot C Difference  
Statistical analysis description 
Response rate analysis of Lot ALot C mean difference.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1263


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[79]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.61  
upper limit 
0.6  
Notes [79]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (5% to 5%). 

Statistical analysis title 
Combined Lots A, B, CControl Difference  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
2202


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[80]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
1.24  
Notes [80]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥5%. 


End point title 
Percentage of Subjects Responding to Poliovirus Type 3  
End point description 
Subject serum samples were collected for testing with a microneutralization inhibition test for neutralizing antibodies to Poliovirus Type 3. Sera response or endpoint is defined as a titer ≥8. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Secondary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Lot ALot B Difference  
Statistical analysis description 
Response rate analysis of Lot ALot B mean difference.


Comparison groups 
V419 Lot A v V419 Lot B


Number of subjects included in analysis 
1249


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[81]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.61  
upper limit 
0.61  
Notes [81]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (5% to 5%). 

Statistical analysis title 
Lot BLot C Difference  
Statistical analysis description 
Response rate analysis of Lot BLot C mean difference.


Comparison groups 
V419 Lot B v V419 Lot C


Number of subjects included in analysis 
1250


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[82]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.61  
upper limit 
0.61  
Notes [82]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (5% to 5%). 

Statistical analysis title 
Lot ALot C Difference  
Statistical analysis description 
Response rate analysis of Lot ALot C mean difference.


Comparison groups 
V419 Lot A v V419 Lot C


Number of subjects included in analysis 
1249


Analysis specification 
Prespecified


Analysis type 
equivalence ^{[83]}  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.61  
upper limit 
0.61  
Notes [83]  Response rate differences were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Equivalence required that the lower and upper limits of the 95% confidence interval of the response rates between any 2 lots were within the equivalence margin (5% to 5%). 

Statistical analysis title 
Combined Lots A, B, CControl Difference  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
2178


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[84]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.33


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.05  
upper limit 
1.85  
Notes [84]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥5%. 


End point title 
Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Toxin  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis toxin. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 4.


End point type 
Secondary


End point timeframe 
Postdose 4 (Month 16)




Statistical analysis title 
Combined Lots A, B, and C/Control Ratio  
Statistical analysis description 
GMC ratio (Combined Lots A, B, and C/Control)


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2015


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[85]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
1.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.98  
upper limit 
1.17  
Notes [85]  The estimates for GMC, GMC ratio, and pvalue are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 


End point title 
Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Filamentous Hemagglutinin (FHA)  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 4.


End point type 
Secondary


End point timeframe 
Postdose 4 (Month 16)




Statistical analysis title 
Combined Lots A, B, and C/Control Ratio  
Statistical analysis description 
GMC ratio (Combined Lots A, B, and C/Control)


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2013


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[86]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
0.86


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.79  
upper limit 
0.95  
Notes [86]  The estimates for GMC, GMC ratio, and pvalue are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 


End point title 
Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Pertactin  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 4.


End point type 
Secondary


End point timeframe 
Postdose 4 (Month 16)




Statistical analysis title 
Combined Lots A, B, and C/Control Ratio  
Statistical analysis description 
GMC ratio (Combined Lots A, B, and C/Control)


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2017


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[87]}  
Pvalue 
= 0.035  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
0.74


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.66  
upper limit 
0.83  
Notes [87]  The estimates for GMC, GMC ratio, and pvalue are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 


End point title 
Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Fimbriae  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 4.


End point type 
Secondary


End point timeframe 
Postdose 4 (Month 16)




Statistical analysis title 
Combined Lots A, B, and C/Control Ratio  
Statistical analysis description 
GMC ratio (Combined Lots A, B, and C/Control)


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2017


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[88]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
1.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.17  
upper limit 
1.46  
Notes [88]  The estimates for GMC, GMC ratio, and pvalue are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 


End point title 
Percentage of Subjects Responding to Pertussis Toxin  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis toxin. Sera response or endpoint was defined as follows: 1) if the predose titer was <4X LLOQ then the postdose titer was ≥4X LLOQ; 2) if the predose titer was ≥4X LLOQ then the postdose titer was ≥ the predose titer. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 4.


End point type 
Secondary


End point timeframe 
Postdose 4 (Month 16)




Statistical analysis title 
Combined Lots A, B, CControl Difference  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
1870


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[89]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.11  
upper limit 
2.58  
Notes [89]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥10%. 


End point title 
Percentage of Subjects Responding to Pertussis Filamentous Hemagglutinin (FHA)  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin. Sera response or endpoint was defined as follows: (1) if the predose titer was <4X LLOQ then the postdose titer was ≥4X LLOQ; (2) if the predose titer was ≥4X LLOQ then the post dose titer was ≥ the predose titer. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 4.


End point type 
Secondary


End point timeframe 
Postdose 4 (Month 16)




Statistical analysis title 
Combined Lots A, B, CControl Difference  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
1930


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[90]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
0.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.41  
upper limit 
3.22  
Notes [90]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥10%. 


End point title 
Percentage of Subjects Responding to Pertussis Pertactin (PRN)  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin. Sera response or endpoint was defined as follows: (1) if the predose titer was <4X LLOQ then the postdose titer was ≥4X LLOQ; (2) if the predose titer was ≥4X LLOQ then the postdose titer was ≥ the predose titer. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 4.


End point type 
Secondary


End point timeframe 
Postdose 4 (Month 16)




Statistical analysis title 
Combined Lots A, B, CControl Difference  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
1866


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[91]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
1.15


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.13  
upper limit 
5.47  
Notes [91]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥10%. 


End point title 
Percentage of Subjects Responding to Pertussis Fimbriae  
End point description 
Subject serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. Sera response or endpoint was defined as follows: (1) if the predose titer was <4X LLOQ then the postdose titer was ≥4X LLOQ; (2) if the predose titer was ≥4X LLOQ then the postdose titer was ≥ the predose titer. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 4.


End point type 
Secondary


End point timeframe 
Postdose 4 (Month 16)




Statistical analysis title 
Combined Lots A, B, CControl Difference  
Statistical analysis description 
Response rate analysis of Combined Lots A, B, and CControl mean difference.


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
1928


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[92]}  
Pvalue 
< 0.001  
Method 
Miettinen and Nurminen  
Parameter type 
Mean difference (final values)  
Point estimate 
3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.39  
upper limit 
7.4  
Notes [92]  Response rate, response rate differences, and pvalues were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥10%. 


End point title 
Geometric Mean Concentrations (GMC) for Antibodies to Pneumococcal Serotypes  
End point description 
Subject serum samples were collected for testing with a multiplex electrochemiluminescencebased detection assay for serotypespecific pneumococcal polysaccharide antibodies. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 3.


End point type 
Secondary


End point timeframe 
Postdose 3 (Month 7)




Statistical analysis title 
Combined Lots A, B, C/Control Ratio; Serotype 1  
Statistical analysis description 
GMC ratio (Combined Lots A, B, C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
1447


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[93]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
0.92


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.82  
upper limit 
1.04  
Notes [93]  The estimates for GMC, GMC ratio, and pvalues are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 

Statistical analysis title 
Combined Lots A, B, C/Control Ratio; Serotype 4  
Statistical analysis description 
GMC ratio (Combined Lots A, B, C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
1447


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[94]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.89  
upper limit 
1.12  
Notes [94]  The estimates for GMC, GMC ratio, and pvalues are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 

Statistical analysis title 
Combined Lots A, B, C/Control Ratio; Serotype 3  
Statistical analysis description 
GMC ratio (Combined Lots A, B, C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
1447


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[95]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
0.95


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.84  
upper limit 
1.06  
Notes [95]  The estimates for GMC, GMC ratio, and pvalues are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 

Statistical analysis title 
Combined Lots A, B, C/Control Ratio; Serotype 5  
Statistical analysis description 
GMC ratio (Combined Lots A, B, C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
1447


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[96]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
0.93


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
1.07  
Notes [96]  The estimates for GMC, GMC ratio, and pvalues are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 

Statistical analysis title 
Combined Lots A, B, C/Control Ratio; Serotype 6A  
Statistical analysis description 
GMC ratio (Combined Lots A, B, C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
1447


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[97]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
0.87


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.77  
upper limit 
0.99  
Notes [97]  The estimates for GMC, GMC ratio, and pvalues are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 

Statistical analysis title 
Combined Lots A, B, C/Control Ratio; Serotype 6B  
Statistical analysis description 
GMC ratio (Combined Lots A, B, C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
1447


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[98]}  
Pvalue 
= 0.055  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
0.79


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.64  
upper limit 
0.96  
Notes [98]  The estimates for GMC, GMC ratio, and pvalues are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 

Statistical analysis title 
Combined Lots A, B, C/Control Ratio; Serotype 9V  
Statistical analysis description 
GMC ratio (Combined Lots A, B, C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
1447


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[99]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.88  
upper limit 
1.13  
Notes [99]  The estimates for GMC, GMC ratio, and pvalues are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 

Statistical analysis title 
Combined Lots A, B, C/Control Ratio; Serotype 7F  
Statistical analysis description 
GMC ratio (Combined Lots A, B, C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
1447


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[100]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
0.89


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
0.99  
Notes [100]  The estimates for GMC, GMC ratio, and pvalues are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 

Statistical analysis title 
Combined Lots A, B, C/Control Ratio; Serotype 14  
Statistical analysis description 
GMC ratio (Combined Lots A, B, C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
1447


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[101]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
0.95


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.82  
upper limit 
1.1  
Notes [101]  The estimates for GMC, GMC ratio, and pvalues are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 

Statistical analysis title 
Combined Lots A, B, C/Control Ratio; Serotype 18C  
Statistical analysis description 
GMC ratio (Combined Lots A, B, C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
1447


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[102]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
0.89


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.79  
upper limit 
1  
Notes [102]  The estimates for GMC, GMC ratio, and pvalues are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 

Statistical analysis title 
Combined Lots A, B, C/Control Ratio; Serotype 19A  
Statistical analysis description 
GMC ratio (Combined Lots A, B, C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
1447


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[103]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
0.91


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
1.03  
Notes [103]  The estimates for GMC, GMC ratio, and pvalues are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 

Statistical analysis title 
Combined Lots A, B, C/Control Ratio; Serotype 19F  
Statistical analysis description 
GMC ratio (Combined Lots A, B, C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
1447


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[104]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
0.97


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.87  
upper limit 
1.08  
Notes [104]  The estimates for GMC, GMC ratio, and pvalues are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 

Statistical analysis title 
Combined Lots A, B, C/Control Ratio; Serotype 23F  
Statistical analysis description 
GMC ratio (Combined Lots A, B, C/Control)


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
1447


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[105]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
GMC Ratio  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.77  
upper limit 
1.06  
Notes [105]  The estimates for GMC, GMC ratio, and pvalues are based on an ANCOVA model with natural logtransformed postvaccination titer as the response variable, and vaccination group, natural logtransformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Noninferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67. 


End point title 
Percentage of Subjects Reporting Solicited Injectionsite and Systemic Reactions Within Five Days Following Any Infant Dose Vaccination in the V419 and Control Groups ^{[106]}  
End point description 
Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability. Grade 3 Solicited injection site reaction: Pain, Cries when injected limb is moved or the movement of the injected limb is reduced; Erythema and Swelling, >5 cm. Grade 3 Solicited systemic reactions: Fever (Pyrexia), ≥39.5°C rectal; Vomiting, ≥6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, >3 hours; Drowsiness (Somnolence), Sleeping most of the time or difficult to wake up; Appetite lost, Refuses ≥3 feeds or refuses most feeds; Irritability, Inconsolable.


End point type 
Secondary


End point timeframe 
Day 0 up to Day 5 postany infant dose vaccination


Notes [106]  The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: A descriptive analysis was performed for this outcome. 



No statistical analyses for this end point 


End point title 
Percentage of Subjects With Elevated Temperature By Severity Within Five Days Following Any Infant Dose Vaccination in the V419 and Control Groups  
End point description 
Maximum temperature (all routes) was based on actual temperatures recorded with no adjustments to the measurement route. Maximum temperature (rectal) was required of all subjects if the reading by another method was ≥38.0°C. Percentages were based on the number of subjects in the population with safety followup and temperature data.


End point type 
Secondary


End point timeframe 
Day 0 up to Day 5 postany Infant dose




Statistical analysis title 
Estimated Difference; All routes, <38Â°C  
Statistical analysis description 
The estimated difference was calculated for V419 group minus the Control group.


Comparison groups 
Control v Combined Lot A, B, and C


Number of subjects included in analysis 
2686


Analysis specification 
Prespecified


Analysis type 
other ^{[107]}  
Method 

Parameter type 
Mean difference (final values)  
Point estimate 
13.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
18.8  
upper limit 
8.4  
Notes [107]  The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method. 

Statistical analysis title 
Est. Difference; All routes, â‰¥38.5Â°C and <39.5Â°C  
Statistical analysis description 
The estimated difference was calculated for V419 group minus the Control group.


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2686


Analysis specification 
Prespecified


Analysis type 
other ^{[108]}  
Method 

Parameter type 
Mean difference (final values)  
Point estimate 
8.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.8  
upper limit 
11.9  
Notes [108]  The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method. 

Statistical analysis title 
Est. Difference; All routes, â‰¥38Â°C and <38.5Â°  
Statistical analysis description 
The estimated difference was calculated for V419 group minus the Control group.


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2686


Analysis specification 
Prespecified


Analysis type 
other ^{[109]}  
Method 

Parameter type 
Mean difference (final values)  
Point estimate 
3.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
8.3  
Notes [109]  The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method. 

Statistical analysis title 
Est. Difference; All routes, â‰¥39.5Â°C  
Statistical analysis description 
The estimated difference was calculated for V419 group minus the Control group.


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2686


Analysis specification 
Prespecified


Analysis type 
other ^{[110]}  
Method 

Parameter type 
Mean difference (final values)  
Point estimate 
1.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
2.2  
Notes [110]  The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method. 

Statistical analysis title 
Estimated Difference; Rectal, <38Â°C  
Statistical analysis description 
The estimated difference was calculated for V419 group minus the Control group.


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2686


Analysis specification 
Prespecified


Analysis type 
other ^{[111]}  
Method 

Parameter type 
Mean difference (final values)  
Point estimate 
11.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
16.6  
upper limit 
5.9  
Notes [111]  The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method. 

Statistical analysis title 
Estimated Difference; Rectal, â‰¥38Â°C and <38.5Â°C  
Statistical analysis description 
The estimated difference was calculated for V419 group minus the Control group.


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2686


Analysis specification 
Prespecified


Analysis type 
other ^{[112]}  
Method 

Parameter type 
Mean difference (final values)  
Point estimate 
3.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.4  
upper limit 
7.8  
Notes [112]  The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method. 

Statistical analysis title 
Estimated Difference; Rectal, â‰¥39.5Â°C  
Statistical analysis description 
The estimated difference was calculated for V419 group minus the Control group.


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2686


Analysis specification 
Prespecified


Analysis type 
other ^{[113]}  
Method 

Parameter type 
Mean difference (final values)  
Point estimate 
1.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
2.1  
Notes [113]  The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method. 

Statistical analysis title 
Estimated Difference; Rectal, â‰¥38.5Â°C and <39.5Â°C  
Statistical analysis description 
The estimated difference was calculated for V419 group minus the Control group.


Comparison groups 
Combined Lot A, B, and C v Control


Number of subjects included in analysis 
2686


Analysis specification 
Prespecified


Analysis type 
other ^{[114]}  
Method 

Parameter type 
Mean difference (final values)  
Point estimate 
8.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.6  
upper limit 
11.6  
Notes [114]  The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method. 


Adverse events information


Timeframe for reporting adverse events 
SAEs: up to 6 months after vaccination 3 (the last infant vaccination) and up to 15 days after vaccination 4 (the toddler vaccination); Vaccinerelated SAEs and deaths: up to Month 16 (duration of study); Other AEs: up to 15 days after any vaccination


Adverse event reporting additional description 
The All Subjects as Treated population included all randomized subjects who received at least one dose of study vaccine and had safety follow up. For safety analysis, subjects who received the 3 V419 lots were combined.


Assessment type 
Systematic  
Dictionary used for adverse event reporting


Dictionary name 
MedDRA  
Dictionary version 
16.1


Reporting groups


Reporting group title 
V419 (Combined Lots A, B, and C)


Reporting group description 
V419 (Combined Lots A, B, and C) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; Pentacel™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.  
Reporting group title 
Control


Reporting group description 
Pentacel™ 0.5 mL IM at 2, 4, 6, and 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age; and Modified Process Hepatitis B vaccine 0.5 mL IM at 2 and 6 months of age.  
