Download PDF

Clinical Trial Results:
A Phase III Randomized, Partially Double-Blind, Active-Comparator-Controlled, Lot-to-Lot 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	2011-004108-39
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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

V419-006

ISRCTN number

US NCT number

NCT01340937

WHO universal trial number (UTN)

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., 800 672-6372, ClinicalTrialsDisclosure@merck.com

Scientific contact

VP, Late Stage Development, Merck Sharp and Dohme Corp., A Subsidiary of Merck & Co., Inc., 800 672-6372, ClinicalTrialsDisclosure@merck.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-000394-PIP01-08

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

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

Yes

Analysis stage

Final

Date of interim/final analysis

26 Jul 2013

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

26 Jul 2013

Was the trial ended prematurely?

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 follow-up planned

Independent data monitoring committee (IDMC) involvement?

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

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

2808

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

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

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 title

Infant Series

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Assessor

Blinding implementation details

This was a partially double-blind 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).

Are arms mutually exclusive

Yes

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.

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.

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.

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.

Number of subjects in period 1	V419 Lot A	V419 Lot B	V419 Lot C	Control
Started	800	797	809	402
Completed	742	737	753	370
Not completed	58	60	56	32
Physician decision	2	3	1	-
Consent withdrawn by subject	33	32	30	15
Adverse event, non-fatal	-	1	4	-
Death	2	-	2	-
Randomized but not vaccinated	-	5	2	1
Lost to follow-up	20	14	12	13
Protocol deviation	1	4	4	3
Other protocol criterion not met	-	1	1	-

Period 2 title

Interim Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

V419 Lot A

Arm description

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.

V419 Lot B

Arm description

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.

V419 Lot C

Arm description

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.

Control

Arm description

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.

Number of subjects in period 2	V419 Lot A	V419 Lot B	V419 Lot C	Control
Started	742	737	753	370
Completed	675	658	669	329
Not completed	67	79	84	41
Consent withdrawn by subject	28	23	17	12
Physician decision	-	1	1	-
Adverse event, non-fatal	1	-	1	-
Lost to follow-up	29	48	53	23
Other technical problems	4	4	6	3
Protocol deviation	5	3	6	3

Period 3 title

Toddler Vaccinations

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

V419 Lot A

Arm description

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.

V419 Lot B

Arm description

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.

V419 Lot C

Arm description

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.

Control

Arm description

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.

Number of subjects in period 3	V419 Lot A	V419 Lot B	V419 Lot C	Control
Started	675	658	669	329
Completed	666	641	660	319
Not completed	9	17	9	10
Consent withdrawn by subject	2	2	1	1
Lost to follow-up	6	14	7	8
Other technical problems	1	1	1	-
Protocol deviation	-	-	-	1

Period 4 title

Combined Lots

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst, Assessor

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.

Are arms mutually exclusive

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.

Control

Arm description

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.

Number of subjects in period 4	Combined Lot A, B, and C	Control
Started	2406	402
Completed	1974	370
Not completed	432	32
Physician decision	8	-
Consent withdrawn by subject	168	15
Technical problems	17	-
Adverse event, non-fatal	7	-
Death	4	-
Randomized but not vaccinated	-	1
Not specified	2	-
Lost to follow-up	203	13
Protocol deviation	23	3

Baseline characteristics

Top of page

Reporting group title

V419 Lot A

Reporting group description

Reporting group title

V419 Lot B

Reporting group description

Reporting group title

V419 Lot C

Reporting group description

Reporting group title

Control

Reporting group description

Reporting group values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Total
Number of subjects	800	797	809	402	2808
Age categorical
Units: Subjects
In utero	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0
Infants and toddlers (28 days-23 months)	800	797	809	402	2808
Children (2-11 years)	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0
Adults (18-64 years)	0	0	0	0	0
From 65-84 years	0	0	0	0	0
85 years and over	0	0	0	0	0
Age continuous
Units: days
arithmetic mean (standard deviation)	64.6 ( 6.7 )	64.4 ( 6.2 )	64.7 ( 6.6 )	64.3 ( 6.6 )	-
Gender categorical
Units: Subjects
Female	377	366	380	215	1338
Male	423	431	429	187	1470

End points

Top of page

Reporting group title

V419 Lot A

Reporting group description

Reporting group title

V419 Lot B

Reporting group description

Reporting group title

V419 Lot C

Reporting group description

Reporting group title

Control

Reporting group description

Reporting group title

V419 Lot A

Reporting group description

Reporting group title

V419 Lot B

Reporting group description

Reporting group title

V419 Lot C

Reporting group description

Reporting group title

Control

Reporting group description

Reporting group title

V419 Lot A

Reporting group description

Reporting group title

V419 Lot B

Reporting group description

Reporting group title

V419 Lot C

Reporting group description

Reporting group title

Control

Reporting group description

Reporting group title

Combined Lot A, B, and C

Reporting group description

Reporting group title

Control

Reporting group description

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Polyribosylribitol Phosphate (PRP) Antigen

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	604	596	595	288	1795
Units: µg/mL
geometric mean (confidence interval 95%)
GMC for antibodies to PRP	5.51 (4.88 to 6.21)	6.1 (5.38 to 6.92)	6.59 (5.8 to 7.47)	3.76 (3.11 to 4.55)	6.05 (5.63 to 6.5)

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

Pre-specified

Analysis type

equivalence ^[1]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot B)

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.08

Notes
[1] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[2]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot C)

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.02

Notes
[2] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[3]

Method

ANCOVA

Parameter type

GMC ratio (Lot B/Lot C)

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.12

Notes
[3] - The estimates for GMC ratio is based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

non-inferiority ^[4]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC ratio (Combined/Control)

Point estimate

1.63

Confidence interval

level

95%

sides

2-sided

lower limit

1.35

upper limit

1.98

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

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Hepatitis B Surface Antigen

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control
Number of subjects analysed	588	599	580	286
Units: mIU/mL
geometric mean (confidence interval 95%)
GMC for antibodies to Hepatitis B Surface Antigen	1195.96 (1081.62 to 1322.39)	1376.86 (1264.74 to 1498.92)	1414.52 (1297.52 to 1542.06)	609.08 (515.29 to 719.93)

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

Pre-specified

Analysis type

equivalence ^[5]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot B)

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

0.98

Notes
[5] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[6]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot C)

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

0.96

Notes
[6] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[7]

Method

ANCOVA

Parameter type

GMC ratio (Lot B/Lot C)

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.11

Notes
[7] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Diphtheria Toxin

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control
Number of subjects analysed	622	625	618	301
Units: IU/mL
geometric mean (confidence interval 95%)
GMC for Antibodies to Diphtheria Toxin	0.37 (0.34 to 0.4)	0.36 (0.33 to 0.4)	0.38 (0.34 to 0.41)	0.4 (0.35 to 0.45)

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

Pre-specified

Analysis type

equivalence ^[8]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot B)

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.07

Notes
[8] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[9]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot C)

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.09

Notes
[9] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[10]

Method

ANCOVA

Parameter type

GMC ratio (Lot B/Lot C)

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

1.14

Notes
[10] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Tetanus Toxin

Top of page

End point title

Geometric Mean Concentrations (GMC) for Antibodies to Tetanus Toxin

End point description

Subject serum samples were collected for testing with an enzyme-linked immunosorbent assay (ELISA) for anti-tetanus 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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control
Number of subjects analysed	622	609	612	300
Units: IU/mL
geometric mean (confidence interval 95%)
GMC for Antibodies to Tetanus Toxin	1.59 (1.51 to 1.67)	1.63 (1.55 to 1.71)	1.55 (1.48 to 1.63)	0.89 (0.81 to 0.97)

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

Pre-specified

Analysis type

equivalence ^[11]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot B)

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.91

upper limit

1.04

Notes
[11] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[12]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot C)

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

1.09

Notes
[12] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[13]

Method

ANCOVA

Parameter type

GMC ratio (Lot B/Lot C)

Point estimate

1.05

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

1.13

Notes
[13] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Toxin

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	647	634	622	309	1903
Units: EU/mL
geometric mean (confidence interval 95%)
GMC for Antibodies to Pertussis Toxin	100.83 (95.98 to 105.91)	96.82 (92.1 to 101.79)	98.52 (93.84 to 103.43)	82.45 (77.26 to 87.98)	98.72 (95.96 to 101.57)

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

Pre-specified

Analysis type

equivalence ^[14]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot B)

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.1

Notes
[14] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[15]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot C)

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

1.09

Notes
[15] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[16]

Method

ANCOVA

Parameter type

GMC ratio (Lot B/Lot C)

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

1.06

Notes
[16] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

non-inferiority ^[17]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC ratio (Combined Lots/Control)

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.11

upper limit

1.29

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

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Filamentous Hemagglutinin (FHA)

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	644	631	628	312	1903
Units: EU/mL
geometric mean (confidence interval 95%)
GMC for Antibodies to Pertussis FHA	43.98 (41.45 to 46.66)	49.19 (46.52 to 52.02)	56.93 (53.73 to 60.31)	73.25 (67.94 to 78.97)	49.7 (48.06 to 51.4)

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

Pre-specified

Analysis type

equivalence ^[18]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot B)

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

0.96

Notes
[18] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[19]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot C)

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

0.83

Notes
[19] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[20]

Method

ANCOVA

Parameter type

GMC ratio (Lot B/Lot C)

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

0.94

Notes
[20] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

non-inferiority ^[21]

P-value

= 0.419

Method

ANCOVA

Parameter type

GMC ratio (Combined Lots/Control)

Point estimate

0.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

0.73

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

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Pertactin

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	632	616	611	303	1859
Units: EU/mL
geometric mean (confidence interval 95%)
GMC for Antibodies to Pertussis Pertactin	51.3 (47.46 to 55.44)	52.32 (47.85 to 57.21)	54.78 (50.33 to 59.61)	50.96 (45.38 to 57.21)	52.76 (50.27 to 55.37)

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

Pre-specified

Analysis type

equivalence ^[22]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot B)

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.09

Notes
[22] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[23]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot C)

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.05

Notes
[23] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[24]

Method

ANCOVA

Parameter type

GMC ratio (Lot B/Lot C)

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.08

Notes
[24] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

non-inferiority ^[25]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC ratio (Combined Lots/Control)

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

1.17

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

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Fimbriae

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	641	632	623	309	1896
Units: EU/mL
geometric mean (confidence interval 95%)
GMC for Antibodies to Pertussis Fimbriae	228.78 (213.87 to 244.73)	286.74 (268.86 to 305.81)	283.28 (264.52 to 303.36)	175.65 (159.14 to 193.87)	264.61 (254.54 to 275.07)

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

Pre-specified

Analysis type

equivalence ^[26]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot B)

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

0.85

Notes
[26] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[27]

Method

ANCOVA

Parameter type

GMC ratio (Lot A/Lot C)

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

0.87

Notes
[27] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[28]

Method

ANCOVA

Parameter type

GMC ratio (Lot B/Lot C)

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.11

Notes
[28] - The estimates for GMC ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

non-inferiority ^[29]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC ratio (Combined Lots/Control)

Point estimate

1.51

Confidence interval

level

95%

sides

2-sided

lower limit

1.37

upper limit

1.66

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

Primary: Geometric Mean Titer (GMT) for Antibodies to Poliovirus Type 1

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control
Number of subjects analysed	630	632	628	307
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
GMT for Antibodies to Poliovirus Type 1	579.77 (533.82 to 629.68)	684.68 (628.4 to 746.01)	666.18 (612.3 to 724.79)	269.95 (232.21 to 313.83)

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

Pre-specified

Analysis type

equivalence ^[30]

Method

ANCOVA

Parameter type

GMT ratio (Lot A/Lot B)

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

0.96

Notes
[30] - The estimates for GMT ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[31]

Method

ANCOVA

Parameter type

GMT ratio (Lot A/Lot C)

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

0.99

Notes
[31] - The estimates for GMT ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[32]

Method

ANCOVA

Parameter type

GMT ratio (Lot B/Lot C)

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

1.15

Notes
[32] - The estimates for GMT ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

Primary: Geometric Mean Titer (GMT) for Antibodies to Poliovirus Type 2

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control
Number of subjects analysed	630	632	633	307
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
GMT to Antibodies to Poliovirus Type 2	1212.4 (1116.4 to 1316.65)	1276.56 (1172.86 to 1389.43)	1359.78 (1248.13 to 1481.42)	846.14 (751.81 to 952.3)

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

Pre-specified

Analysis type

equivalence ^[33]

Method

ANCOVA

Parameter type

GMT ratio (Lot A/Lot B)

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.05

Notes
[33] - The estimates for GMT ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[34]

Method

ANCOVA

Parameter type

GMT ratio (Lot B/Lot C)

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.09

Notes
[34] - The estimates for GMT ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[35]

Method

ANCOVA

Parameter type

GMT ratio (Lot A/Lot C)

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.02

Notes
[35] - The estimates for GMT ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

Primary: Geometric Mean Titer (GMT) for Antibodies to Poliovirus Type 3

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control
Number of subjects analysed	624	625	625	304
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
GMT for Antibodies to Poliovirus Type 3	901.7 (819.52 to 992.12)	851.34 (772.96 to 937.66)	825.31 (746.52 to 912.42)	784.24 (682.28 to 901.44)

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

Pre-specified

Analysis type

equivalence ^[36]

Method

ANCOVA

Parameter type

GMT ratio (Lot A/Lot B)

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

1.22

Notes
[36] - The estimates for GMT ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[37]

Method

ANCOVA

Parameter type

GMT ratio (Lot B/Lot C)

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

1.19

Notes
[37] - The estimates for GMT ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

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

Pre-specified

Analysis type

equivalence ^[38]

Method

ANCOVA

Parameter type

GMT ratio (Lot A/Lot C)

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

1.26

Notes
[38] - The estimates for GMT ratio are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, 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).

Secondary: Percentage of Subjects Responding to Polyribosylribitol Phosphate (PRP) Antigen

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	604	596	596	288	1795
Units: Percentage of subjects
number (confidence interval 95%)
PRP titer ≥1 µg/mL	86.75 (83.79 to 89.36)	87.25 (84.3 to 89.82)	88.4 (85.55 to 90.86)	79.51 (74.39 to 84.02)	87.47 (85.84 to 88.96)
PRP titer ≥0.15 µg/mL	99.01 (97.85 to 99.63)	98.32 (96.94 to 99.19)	97.82 (96.29 to 98.83)	96.18 (93.27 to 98.08)	98.38 (97.69 to 98.92)

Lot A-Lot B Difference ≥1 ug/mL

Statistical analysis description

Response rate analysis of Lot A-Lot B mean difference.

Comparison groups

V419 Lot A v V419 Lot B

Number of subjects included in analysis

1200

Analysis specification

Pre-specified

Analysis type

equivalence ^[39]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-0.48

Confidence interval

level

95%

sides

2-sided

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%).

Lot A-Lot C Difference ≥1 ug/mL

Statistical analysis description

Response rate analysis of Lot A-Lot C mean difference.

Comparison groups

V419 Lot A v V419 Lot C

Number of subjects included in analysis

1200

Analysis specification

Pre-specified

Analysis type

equivalence ^[40]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-1.62

Confidence interval

level

95%

sides

2-sided

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%).

Lot B-Lot C Difference ≥1 ug/mL

Statistical analysis description

Response rate analysis of Lot B-Lot C mean difference.

Comparison groups

V419 Lot B v V419 Lot C

Number of subjects included in analysis

1192

Analysis specification

Pre-specified

Analysis type

equivalence ^[41]

Method

Parameter type

Mean difference (final values)

Point estimate

-1.16

Confidence interval

level

95%

sides

2-sided

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%).

Combined Lots A, B, C-Control Difference ≥1 ug/mL

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Control v Combined Lot A, B, and C

Number of subjects included in analysis

2083

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[42]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

7.93

Confidence interval

level

95%

sides

2-sided

lower limit

3.38

upper limit

13.17

Notes
[42] - Response rate, response rate differences, and p-values were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥-10%.

Combined Lots-Control Difference ≥ 0.15 ug/mL

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Combined Lot A, B, and C v Control

Number of subjects included in analysis

2083

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[43]

P-value

< 0.001 ^[44]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

2.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

5.12

Notes
[43] - Response rate, response rate differences, and p-values were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥-5%.
[44] - One-sided p-value

Secondary: Percentage of Subjects Responding to Hepatitis B Surface Antigen

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	588	599	580	286	1767
Units: Percentage of subjects
number (confidence interval 95%)
Percentage of Subjects Responding to Hepatitis B	99.66 (98.78 to 99.96)	100 (99.39 to 100)	100 (99.37 to 100)	98.95 (96.97 to 99.78)	99.89 (99.59 to 99.99)

Lot A-Lot B Difference

Statistical analysis description

Response rate analysis of Lot A-Lot B mean difference.

Comparison groups

V419 Lot A v V419 Lot B

Number of subjects included in analysis

1187

Analysis specification

Pre-specified

Analysis type

equivalence ^[45]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-0.34

Confidence interval

level

95%

sides

2-sided

lower limit

-1.23

upper limit

0.3

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%).

Lot A-Lot C Difference

Statistical analysis description

Response rate analysis of Lot A-Lot C mean difference.

Comparison groups

V419 Lot A v V419 Lot C

Number of subjects included in analysis

1168

Analysis specification

Pre-specified

Analysis type

equivalence ^[46]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-0.34

Confidence interval

level

95%

sides

2-sided

lower limit

-1.23

upper limit

0.32

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%).

Lot B-Lot C Difference

Statistical analysis description

Response rate analysis of Lot B-Lot C mean difference.

Comparison groups

V419 Lot B v V419 Lot C

Number of subjects included in analysis

1179

Analysis specification

Pre-specified

Analysis type

equivalence ^[47]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

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%).

Combined Lots A, B, C-Control Difference

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Control v Combined Lot A, B, and C

Number of subjects included in analysis

2053

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[48]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

2.9

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

Secondary: Percentage of Subjects Responding to Diphtheria Toxin

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	622	625	618	301	1865
Units: Percentage of subjects
number (confidence interval 95%)
Percentage of Subjects Responding to Diphtheria	85.05 (82 to 87.76)	84.8 (81.74 to 87.52)	86.41 (83.45 to 89.01)	87.71 (83.46 to 91.2)	85.42 (83.73 to 86.99)

Lot A-Lot B Difference

Statistical analysis description

Response rate analysis of Lot A-Lot B mean difference.

Comparison groups

V419 Lot A v V419 Lot B

Number of subjects included in analysis

1247

Analysis specification

Pre-specified

Analysis type

equivalence ^[49]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

0.25

Confidence interval

level

95%

sides

2-sided

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%).

Lot B-Lot C Difference

Statistical analysis description

Response rate analysis of Lot B-Lot C mean difference.

Comparison groups

V419 Lot B v V419 Lot C

Number of subjects included in analysis

1243

Analysis specification

Pre-specified

Analysis type

equivalence ^[50]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-1.64

Confidence interval

level

95%

sides

2-sided

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%).

Lot A-Lot C Difference

Statistical analysis description

Response rate analysis of Lot A-Lot C mean difference.

Comparison groups

V419 Lot A v V419 Lot C

Number of subjects included in analysis

1240

Analysis specification

Pre-specified

Analysis type

equivalence ^[51]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-1.35

Confidence interval

level

95%

sides

2-sided

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%).

Combined Lots A, B, C-Control Difference

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Control v Combined Lot A, B, and C

Number of subjects included in analysis

2166

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[52]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-2.35

Confidence interval

level

95%

sides

2-sided

lower limit

-6.02

upper limit

2.09

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

Secondary: Percentage of Subjects Responding to Tetanus Toxin

Top of page

End point title

Percentage of Subjects Responding to Tetanus Toxin

End point description

Subject serum samples were collected for testing with an ELISA for anti-tetanus 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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	622	609	612	300	1843
Units: Percentage of subjects
number (confidence interval 95%)
Percentage of Subjects Responding to Tetanus Toxin	99.84 (99.11 to 100)	100 (99.4 to 100)	100 (99.4 to 100)	98.67 (96.62 to 99.64)	99.95 (99.7 to 100)

Lot A-Lot B Difference

Statistical analysis description

Response rate analysis of Lot A-Lot B mean difference.

Comparison groups

V419 Lot B v V419 Lot A

Number of subjects included in analysis

1231

Analysis specification

Pre-specified

Analysis type

equivalence ^[53]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-0.91

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%).

Lot A-Lot C Difference

Statistical analysis description

Response rate analysis of Lot A-Lot C mean difference.

Comparison groups

V419 Lot A v V419 Lot C

Number of subjects included in analysis

1234

Analysis specification

Pre-specified

Analysis type

equivalence ^[54]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

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%).

Lot B-Lot C Difference

Statistical analysis description

Response rate analysis of Lot B-Lot C mean difference.

Comparison groups

V419 Lot B v V419 Lot C

Number of subjects included in analysis

1221

Analysis specification

Pre-specified

Analysis type

equivalence ^[55]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

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%).

Combined Lots A, B, C-Control Difference

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Combined Lot A, B, and C v Control

Number of subjects included in analysis

2143

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[56]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

1.28

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

3.33

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

Secondary: Percentage of Subjects Responding to Pertussis Toxin

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	596	585	580	289	1761
Units: Percentage of subjects
number (confidence interval 95%)
Percentage of Subjects Responding to Pertussis	99.33 (98.29 to 99.82)	97.61 (96.02 to 98.69)	98.97 (97.76 to 99.62)	97.92 (95.54 to 99.23)	98.64 (97.98 to 99.12)

Lot A-Lot B Difference

Statistical analysis description

Response rate analysis of Lot A-Lot B mean difference.

Comparison groups

V419 Lot A v V419 Lot B

Number of subjects included in analysis

1181

Analysis specification

Pre-specified

Analysis type

equivalence ^[57]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

1.73

Confidence interval

level

95%

sides

2-sided

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%).

Lot A-Lot C Difference

Statistical analysis description

Response rate analysis of Lot A-Lot C mean difference.

Comparison groups

V419 Lot A v V419 Lot C

Number of subjects included in analysis

1176

Analysis specification

Pre-specified

Analysis type

equivalence ^[58]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

0.36

Confidence interval

level

95%

sides

2-sided

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%).

Lot B-Lot C Difference

Statistical analysis description

Response rate analysis of Lot B-Lot C mean difference.

Comparison groups

V419 Lot B v V419 Lot C

Number of subjects included in analysis

1165

Analysis specification

Pre-specified

Analysis type

equivalence ^[59]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-1.36

Confidence interval

level

95%

sides

2-sided

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%).

Combined Lots A, B, C-Control Difference

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Control v Combined Lot A, B, and C

Number of subjects included in analysis

2050

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[60]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

-0.59

upper limit

3.14

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

Secondary: Percentage of Subjects Responding to Pertussis Filamentous Hemagglutinin (FHA)

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	620	615	601	304	1836
Units: Percentage of subjects
number (confidence interval 95%)
Percentage of Subjects Responding to Pertussis FHA	85.97 (82.98 to 88.61)	87.32 (84.43 to 89.84)	89.02 (86.24 to 91.4)	92.11 (88.48 to 94.88)	87.42 (85.81 to 88.9)

Lot A-Lot B Difference

Statistical analysis description

Response rate analysis of Lot A-Lot B mean difference.

Comparison groups

V419 Lot A v V419 Lot B

Number of subjects included in analysis

1235

Analysis specification

Pre-specified

Analysis type

equivalence ^[61]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-1.35

Confidence interval

level

95%

sides

2-sided

lower limit

-5.17

upper limit

2.47

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%).

Lot A-Lot C Difference

Statistical analysis description

Response rate analysis of Lot A-Lot C mean difference.

Comparison groups

V419 Lot A v V419 Lot C

Number of subjects included in analysis

1221

Analysis specification

Pre-specified

Analysis type

equivalence ^[62]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-3.06

Confidence interval

level

95%

sides

2-sided

lower limit

-6.79

upper limit

0.67

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%).

Lot B-Lot C Difference

Statistical analysis description

Response rate analysis of Lot B-Lot C mean difference.

Comparison groups

V419 Lot B v V419 Lot C

Number of subjects included in analysis

1216

Analysis specification

Pre-specified

Analysis type

equivalence ^[63]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-1.71

Confidence interval

level

95%

sides

2-sided

lower limit

-5.37

upper limit

1.94

Notes
[63] - 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%).

Combined Lots A, B, C-Control Difference

Statistical analysis description

Response rate analysis of Combined Lots A, B, C-Control mean difference.

Comparison groups

Control v Combined Lot A, B, and C

Number of subjects included in analysis

2140

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[64]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-4.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.73

upper limit

-0.86

Notes
[64] - Response rate, response rate differences, and p-values were stratified by actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the response rates between any 2 lots was ≥-10%.

Secondary: Percentage of Subjects Responding to Pertussis Pertactin (PRN)

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	590	574	560	286	1724
Units: Percentage of subjects
number (confidence interval 95%)
Percentage of Subjects Responding to Pertussis PRN	81.19 (77.79 to 84.26)	78.4 (74.8 to 81.7)	78.75 (75.13 to 82.07)	76.22 (70.86 to 81.04)	79.47 (77.48 to 81.35)

Lot A-Lot B Difference

Statistical analysis description

Response rate analysis of Lot A-Lot B mean difference.

Comparison groups

V419 Lot A v V419 Lot B

Number of subjects included in analysis

1164

Analysis specification

Pre-specified

Analysis type

equivalence ^[65]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

2.77

Confidence interval

level

95%

sides

2-sided

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%).

Lot A-Lot C Difference

Statistical analysis description

Response rate analysis of Lot A-Lot C mean difference.

Comparison groups

V419 Lot A v V419 Lot C

Number of subjects included in analysis

1150

Analysis specification

Pre-specified

Analysis type

equivalence ^[66]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

2.41

Confidence interval

level

95%

sides

2-sided

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%).

Lot B-Lot C Difference

Statistical analysis description

Response rate analysis of Lot B-Lot C mean difference.

Comparison groups

V419 Lot B v V419 Lot C

Number of subjects included in analysis

1134

Analysis specification

Pre-specified

Analysis type

equivalence ^[67]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-0.36

Confidence interval

level

95%

sides

2-sided

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%).

Combined Lots A, B, C-Control Difference

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Control v Combined Lot A, B, and C

Number of subjects included in analysis

2010

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[68]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

3.28

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

8.85

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

Secondary: Percentage of Subjects Responding to Pertussis Fimbriae

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	613	611	594	298	1818
Units: Percentage of subjects
number (confidence interval 95%)
Subjects Responding to Pertussis Fimbriae	86.95 (84.02 to 89.51)	91 (88.44 to 93.15)	91.08 (88.49 to 93.25)	86.91 (82.55 to 90.53)	89.66 (88.17 to 91.02)

Lot A-Lot B Difference

Statistical analysis description

Response rate analysis of Lot A-Lot B mean difference.

Comparison groups

V419 Lot A v V419 Lot B

Number of subjects included in analysis

1224

Analysis specification

Pre-specified

Analysis type

equivalence ^[69]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-4.12

Confidence interval

level

95%

sides

2-sided

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%).

Lot A-Lot C Difference

Statistical analysis description

Response rate analysis of Lot A-Lot C mean difference.

Comparison groups

V419 Lot A v V419 Lot C

Number of subjects included in analysis

1207

Analysis specification

Pre-specified

Analysis type

equivalence ^[70]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-4.17

Confidence interval

level

95%

sides

2-sided

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%).

Lot B-Lot C Difference

Statistical analysis description

Response rate analysis of Lot B-Lot C mean difference.

Comparison groups

V419 Lot B v V419 Lot C

Number of subjects included in analysis

1205

Analysis specification

Pre-specified

Analysis type

equivalence ^[71]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

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%).

Combined Lots A, B, C-Control Difference

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Combined Lot A, B, and C v Control

Number of subjects included in analysis

2116

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[72]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

2.85

Confidence interval

level

95%

sides

2-sided

lower limit

-0.85

upper limit

7.36

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

Secondary: Percentage of Subjects Responding to Poliovirus Type 1

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	630	632	628	307	1890
Units: Percentage of subjects
number (confidence interval 95%)
Percentage of Subjects Responding to Poliovirus 1	100 (99.42 to 100)	100 (99.42 to 100)	100 (99.41 to 100)	99.35 (97.67 to 99.92)	100 (99.81 to 100)

Lot A-Lot B Difference

Statistical analysis description

Response rate analysis of Lot A-Lot B mean difference.

Comparison groups

V419 Lot A v V419 Lot B

Number of subjects included in analysis

1262

Analysis specification

Pre-specified

Analysis type

equivalence ^[73]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

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%).

Lot A-Lot C Difference

Statistical analysis description

Response rate analysis of Lot A-Lot C mean difference.

Comparison groups

V419 Lot A v V419 Lot C

Number of subjects included in analysis

1258

Analysis specification

Pre-specified

Analysis type

equivalence ^[74]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

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%).

Lot B-Lot C Difference

Statistical analysis description

Response rate analysis of Lot B-Lot C mean difference.

Comparison groups

V419 Lot B v V419 Lot C

Number of subjects included in analysis

1260

Analysis specification

Pre-specified

Analysis type

equivalence ^[75]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

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%).

Combined Lots A, B, C-Control Difference

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Control v Combined Lot A, B, and C

Number of subjects included in analysis

2197

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[76]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

0.18

upper limit

2.36

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

Secondary: Percentage of Subjects Responding to Poliovirus Type 2

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	630	632	633	307	1895
Units: Percentage of subjects
number (confidence interval 95%)
Percentage of Subjects Responding to Poliovirus 2	100 (99.42 to 100)	100 (99.42 to 100)	100 (99.42 to 100)	100 (98.81 to 100)	100 (99.81 to 100)

Lot A-Lot B Difference

Statistical analysis description

Response rate analysis of Lot A-Lot B mean difference.

Comparison groups

V419 Lot A v V419 Lot B

Number of subjects included in analysis

1262

Analysis specification

Pre-specified

Analysis type

equivalence ^[77]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

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%).

Lot A-Lot C Difference

Statistical analysis description

Response rate analysis of Lot A-Lot C mean difference.

Comparison groups

V419 Lot A v V419 Lot C

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

equivalence ^[78]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

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%).

Lot B-Lot C Difference

Statistical analysis description

Response rate analysis of Lot B-Lot C mean difference.

Comparison groups

V419 Lot B v V419 Lot C

Number of subjects included in analysis

1265

Analysis specification

Pre-specified

Analysis type

equivalence ^[79]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

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%).

Combined Lots A, B, C-Control Difference

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Control v Combined Lot A, B, and C

Number of subjects included in analysis

2202

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[80]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

1.24

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

Secondary: Percentage of Subjects Responding to Poliovirus Type 3

Top of page

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)

End point values	V419 Lot A	V419 Lot B	V419 Lot C	Control	Combined Lot A, B, and C
Number of subjects analysed	624	625	625	304	1874
Units: Percentage of subjects
number (confidence interval 95%)
Percentage of Subjects Responding to Poliovirus 3	100 (99.41 to 100)	100 (99.41 to 100)	100 (99.41 to 100)	99.67 (98.18 to 99.99)	100 (99.8 to 100)

Lot A-Lot B Difference

Statistical analysis description

Response rate analysis of Lot A-Lot B mean difference.

Comparison groups

V419 Lot A v V419 Lot B

Number of subjects included in analysis

1249

Analysis specification

Pre-specified

Analysis type

equivalence ^[81]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

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%).

Lot A-Lot C Difference

Statistical analysis description

Response rate analysis of Lot A-Lot C mean difference.

Comparison groups

V419 Lot A v V419 Lot C

Number of subjects included in analysis

1249

Analysis specification

Pre-specified

Analysis type

equivalence ^[82]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

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%).

Lot B-Lot C Difference

Statistical analysis description

Response rate analysis of Lot B-Lot C mean difference.

Comparison groups

V419 Lot B v V419 Lot C

Number of subjects included in analysis

1250

Analysis specification

Pre-specified

Analysis type

equivalence ^[83]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

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%).

Combined Lots A, B, C-Control Difference

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Control v Combined Lot A, B, and C

Number of subjects included in analysis

2178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[84]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

0.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.05

upper limit

1.85

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

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Toxin

Top of page

End point title

Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Toxin

End point description

End point type

Secondary

End point timeframe

Postdose 4 (Month 16)

End point values	Combined Lot A, B, and C	Control
Number of subjects analysed	1744	271
Units: EU/mL
geometric mean (confidence interval 95%)
GMC for Antibodies to Pertussis Toxin	110.61 (106.92 to 114.42)	102.82 (93.7 to 112.82)

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

Pre-specified

Analysis type

non-inferiority ^[85]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

1.17

Notes
[85] - The estimates for GMC, GMC ratio, and p-value are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Filamentous Hemagglutinin (FHA)

Top of page

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)

End point values	Combined Lot A, B, and C	Control
Number of subjects analysed	1742	271
Units: EU/mL
geometric mean (confidence interval 95%)
GMC for Antibodies to Pertussis FHA	106.3 (102.73 to 110)	121 (110.19 to 132.87)

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

Pre-specified

Analysis type

non-inferiority ^[86]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

0.95

Notes
[86] - The estimates for GMC, GMC ratio, and p-value are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Pertactin

Top of page

End point title

Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Pertactin

End point description

End point type

Secondary

End point timeframe

Postdose 4 (Month 16)

End point values	Combined Lot A, B, and C	Control
Number of subjects analysed	1746	271
Units: EU/mL
geometric mean (confidence interval 95%)
GMC for Antibodies to Pertussis Pertactin	104.51 (100.14 to 109.07)	142.32 (126.68 to 159.89)

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

Pre-specified

Analysis type

non-inferiority ^[87]

P-value

= 0.035

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

0.83

Notes
[87] - The estimates for GMC, GMC ratio, and p-value are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Fimbriae

Top of page

End point title

Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Fimbriae

End point description

End point type

Secondary

End point timeframe

Postdose 4 (Month 16)

End point values	Combined Lot A, B, and C	Control
Number of subjects analysed	1746	271
Units: EU/mL
geometric mean (confidence interval 95%)
GMC for Antibodies to Pertussis Fimbriae	451.04 (433.21 to 469.6)	337.79 (299.43 to 381.05)

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

Pre-specified

Analysis type

non-inferiority ^[88]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

1.31

Confidence interval

level

95%

sides

2-sided

lower limit

1.17

upper limit

1.46

Notes
[88] - The estimates for GMC, GMC ratio, and p-value are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

Secondary: Percentage of Subjects Responding to Pertussis Toxin

Top of page

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)

End point values	Combined Lot A, B, and C	Control
Number of subjects analysed	1616	254
Units: Percentage of subjects
number (confidence interval 95%)
Percentage of Subjects Responding to Pertussis	98.51 (97.8 to 99.05)	98.43 (96.02 to 99.57)

Combined Lots A, B, C-Control Difference

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Combined Lot A, B, and C v Control

Number of subjects included in analysis

1870

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[89]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-1.11

upper limit

2.58

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

Secondary: Percentage of Subjects Responding to Pertussis Filamentous Hemagglutinin (FHA)

Top of page

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)

End point values	Combined Lot A, B, and C	Control
Number of subjects analysed	1669	261
Units: Percentage of subjects
number (confidence interval 95%)
Percentage of Subjects Responding to Pertussis FHA	95.33 (94.2 to 96.29)	95.4 (92.11 to 97.6)

Combined Lots A, B, C-Control Difference

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Combined Lot A, B, and C v Control

Number of subjects included in analysis

1930

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[90]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

-0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-2.41

upper limit

3.22

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

Secondary: Percentage of Subjects Responding to Pertussis Pertactin (PRN)

Top of page

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)

End point values	Combined Lot A, B, and C	Control
Number of subjects analysed	1608	258
Units: Percentage of subjects
number (confidence interval 95%)
Percentage of Subjects Responding to Pertussis PRN	92.16 (90.74 to 93.43)	91.09 (86.92 to 94.26)

Combined Lots A, B, C-Control Difference

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Combined Lot A, B, and C v Control

Number of subjects included in analysis

1866

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[91]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

1.15

Confidence interval

level

95%

sides

2-sided

lower limit

-2.13

upper limit

5.47

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

Secondary: Percentage of Subjects Responding to Pertussis Fimbriae

Top of page

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)

End point values	Combined Lot A, B, and C	Control
Number of subjects analysed	1664	264
Units: Percentage of subjects
number (confidence interval 95%)
Subjects Responding to Pertussis Fimbriae	92.97 (91.63 to 94.15)	90.15 (85.9 to 93.47)

Combined Lots A, B, C-Control Difference

Statistical analysis description

Response rate analysis of Combined Lots A, B, and C-Control mean difference.

Comparison groups

Combined Lot A, B, and C v Control

Number of subjects included in analysis

1928

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[92]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.39

upper limit

7.4

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

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pneumococcal Serotypes

Top of page

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 electrochemiluminescence-based detection assay for serotype-specific 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)

End point values	Control	Combined Lot A, B, and C
Number of subjects analysed	191	1256
Units: µg/mL
geometric mean (confidence interval 95%)
Pneumococcal Serotype 1 (n=191, 1256)	1.55 (1.39 to 1.73)	1.44 (1.38 to 1.5)
Pneumococcal Serotype 3 (n=191, 1255)	0.5 (0.45 to 0.56)	0.48 (0.46 to 0.5)
Pneumococcal Serotype 4 (n=189, 1255)	1.22 (1.1 to 1.35)	1.22 (1.17 to 1.27)
Pneumococcal Serotype 5 (n=191, 1256)	1.61 (1.41 to 1.82)	1.49 (1.42 to 1.57)
Pneumococcal Serotype 6A (n=191, 1251)	2.96 (2.64 to 3.32)	2.57 (2.45 to 2.69)
Pneumococcal Serotype 6B (n=190, 1255)	1.29 (1.07 to 1.54)	1.01 (0.94 to 1.09)
Pneumococcal Serotype 7F (n=191, 1256)	3.08 (2.77 to 3.41)	2.74 (2.64 to 2.85)
Pneumococcal Serotype 9V (n=189, 1256)	1.35 (1.19 to 1.52)	1.35 (1.29 to 1.41)
Pneumococcal Serotype 14 (n=191, 1256)	4.83 (4.26 to 5.48)	4.74 (4.48 to 5.01)
Pneumococcal Serotype 18C (n=191, 1253)	1.82 (1.62 to 2.03)	1.62 (1.55 to 1.69)
Pneumococcal Serotype 19A (n=191, 1254)	1.75 (1.55 to 1.99)	1.6 (1.53 to 1.68)
Pneumococcal Serotype 19F (n=191, 1256)	2.26 (2.03 to 2.5)	2.18 (2.1 to 2.27)
Pneumococcal Serotype 23F (n=190, 1254)	1.2 (1.04 to 1.38)	1.1 (1.04 to 1.16)

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

Pre-specified

Analysis type

non-inferiority ^[93]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.04

Notes
[93] - The estimates for GMC, GMC ratio, and p-values are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

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

Pre-specified

Analysis type

non-inferiority ^[94]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.06

Notes
[94] - The estimates for GMC, GMC ratio, and p-values are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

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

Pre-specified

Analysis type

non-inferiority ^[95]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

1.12

Notes
[95] - The estimates for GMC, GMC ratio, and p-values are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

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

Pre-specified

Analysis type

non-inferiority ^[96]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.07

Notes
[96] - The estimates for GMC, GMC ratio, and p-values are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

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

Pre-specified

Analysis type

non-inferiority ^[97]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

0.99

Notes
[97] - The estimates for GMC, GMC ratio, and p-values are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

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

Pre-specified

Analysis type

non-inferiority ^[98]

P-value

= 0.055

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

0.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

0.96

Notes
[98] - The estimates for GMC, GMC ratio, and p-values are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

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

Pre-specified

Analysis type

non-inferiority ^[99]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

0.99

Notes
[99] - The estimates for GMC, GMC ratio, and p-values are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

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

Pre-specified

Analysis type

non-inferiority ^[100]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.13

Notes
[100] - The estimates for GMC, GMC ratio, and p-values are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

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

Pre-specified

Analysis type

non-inferiority ^[101]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.1

Notes
[101] - The estimates for GMC, GMC ratio, and p-values are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

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

Pre-specified

Analysis type

non-inferiority ^[102]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

Notes
[102] - The estimates for GMC, GMC ratio, and p-values are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

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

Pre-specified

Analysis type

non-inferiority ^[103]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.03

Notes
[103] - The estimates for GMC, GMC ratio, and p-values are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

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

Pre-specified

Analysis type

non-inferiority ^[104]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.08

Notes
[104] - The estimates for GMC, GMC ratio, and p-values are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

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

Pre-specified

Analysis type

non-inferiority ^[105]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMC Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.06

Notes
[105] - The estimates for GMC, GMC ratio, and p-values are based on an ANCOVA model with natural log-transformed postvaccination titer as the response variable, and vaccination group, natural log-transformed, prevaccination titer, actual brand of birth dose Hepatitis B vaccine as explanatory variables. Non-inferiority required that the lower limit of the 95% confidence interval of the GMC ratio is ≥0.67.

Secondary: Percentage of Subjects Reporting Solicited Injection-site and Systemic Reactions Within Five Days Following Any Infant Dose Vaccination in the V419 and Control Groups

Top of page

End point title

Percentage of Subjects Reporting Solicited Injection-site 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 post-any 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.

End point values	Control	Combined Lot A, B, and C
Number of subjects analysed	397	2390
Units: Percentage of subjects
number (not applicable)
Any Injection site Erythema	40.8	44.6
Severe Injection site Erythema	0.8	0.3
Any Injection site Pain	72	70
Severe Injection site Pain	5.5	6
Any Injection site Swelling	34.5	34.5
Severe Injection site Swelling	0.5	0.5
Any Crying abnormal	72.5	74.8
Severe Crying abnormal	12.6	9.5
Any Decreased appetite	47.4	48.5
Severe Decreased appetite	1.3	1.4
Any Irritability	79.8	80.7
Severe Irritability	6.5	7.8
Any Pyrexia	33.2	47.1
Severe Pyrexia	1.3	1.4
Any Somnolence	73.3	73.2
Severe Somnolence	3	3.5
Any Vomiting	24.9	26.7
Severe Vomiting	1.5	0.8

No statistical analyses for this end point

Secondary: Percentage of Subjects With Elevated Temperature By Severity Within Five Days Following Any Infant Dose Vaccination in the V419 and Control Groups

Top of page

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 follow-up and temperature data.

End point type

Secondary

End point timeframe

Day 0 up to Day 5 post-any Infant dose

End point values	Combined Lot A, B, and C	Control
Number of subjects analysed	2308	378
Units: Percentage of subjects
number (not applicable)
Maximum temperature (all routes); <38.0°C	50.8	64.6
Max. temp. (all routes); ≥38.0°C and <38.5°C; mild	27.2	23.3
Max. (all routes); ≥38.5°C and <39.5°C; moderate	19.5	10.8
Max. temp. (all routes); ≥39.5°C; severe	2.4	1.3
Maximum temperature (rectal); <38.0°C	47.7	59
Max. temp. (rectal); ≥38.0°C and <38.5°C; mild	26.5	23
Max. temp. (rectal); ≥38.5°C and <39.5°C; moderate	19	10.6
Max. temp. (rectal); ≥39.5°C; severe	2.4	1.3

Estimated Difference; All routes, <38°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

Pre-specified

Analysis type

other ^[107]

Method

Parameter type

Mean difference (final values)

Point estimate

-13.7

Confidence interval

level

95%

sides

2-sided

lower limit

-18.8

upper limit

-8.4

Notes
[107] - The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method.

Est. Difference; All routes, ≥38.5°C and <39.5°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

Pre-specified

Analysis type

other ^[108]

Method

Parameter type

Mean difference (final values)

Point estimate

8.7

Confidence interval

level

95%

sides

2-sided

lower limit

4.8

upper limit

11.9

Notes
[108] - The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method.

Est. Difference; All routes, ≥38°C and <38.5°

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

Pre-specified

Analysis type

other ^[109]

Method

Parameter type

Mean difference (final values)

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

8.3

Notes
[109] - The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method.

Est. Difference; All routes, ≥39.5°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

Pre-specified

Analysis type

other ^[110]

Method

Parameter type

Mean difference (final values)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

2.2

Notes
[110] - The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method.

Estimated Difference; Rectal, <38°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

Pre-specified

Analysis type

other ^[111]

Method

Parameter type

Mean difference (final values)

Point estimate

-11.3

Confidence interval

level

95%

sides

2-sided

lower limit

-16.6

upper limit

-5.9

Notes
[111] - The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method.

Estimated Difference; Rectal, ≥38°C and <38.5°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

Pre-specified

Analysis type

other ^[112]

Method

Parameter type

Mean difference (final values)

Point estimate

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

7.8

Notes
[112] - The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method.

Estimated Difference; Rectal, ≥38.5°C and <39.5°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

Pre-specified

Analysis type

other ^[113]

Method

Parameter type

Mean difference (final values)

Point estimate

8.4

Confidence interval

level

95%

sides

2-sided

lower limit

4.6

upper limit

11.6

Notes
[113] - The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method.

Estimated Difference; Rectal, ≥39.5°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

Pre-specified

Analysis type

other ^[114]

Method

Parameter type

Mean difference (final values)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

2.1

Notes
[114] - The 95% confidence intervals were based on the unstratified Miettinen and Nurminen method.

Adverse events

Top of page

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); Vaccine-related 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 name

MedDRA

Dictionary version

16.1

Reporting group title

V419 (Combined Lots A, B, and C)

Reporting group description

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.

Serious adverse events	V419 (Combined Lots A, B, and C)	Control
Total subjects affected by serious adverse events
subjects affected / exposed	94 / 2390 (3.93%)	15 / 397 (3.78%)
number of deaths (all causes)	5	0
number of deaths resulting from adverse events	0	0
Injury, poisoning and procedural complications
Brain contusion
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skull fracture
subjects affected / exposed	3 / 2390 (0.13%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Clavicle fracture
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Craniocerebral injury
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	0 / 2390 (0.00%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subdural haemorrhage
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	0 / 2390 (0.00%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Cyanosis
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Hydrocephalus
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Pneumocephalus
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile convulsion
subjects affected / exposed	4 / 2390 (0.17%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	1 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	4 / 2390 (0.17%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	3 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sudden infant death syndrome
subjects affected / exposed	2 / 2390 (0.08%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0
Death
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Irritability
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Idiopathic thrombocytopenic purpura
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphadenitis
subjects affected / exposed	1 / 2390 (0.04%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	2 / 2390 (0.08%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	2 / 2390 (0.08%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intussusception
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Crohn's disease
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Duodenal ulcer
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haematemesis
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Apnoeic attack
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Asthma
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atelectasis
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchial hyperreactivity
subjects affected / exposed	2 / 2390 (0.08%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 2390 (0.00%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	2 / 2390 (0.08%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Hydronephrosis
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Pneumonia respiratory syncytial viral
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus bronchiolitis
subjects affected / exposed	12 / 2390 (0.50%)	4 / 397 (1.01%)
occurrences causally related to treatment / all	0 / 12	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 2390 (0.04%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Upper respiratory tract infection
subjects affected / exposed	3 / 2390 (0.13%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	2 / 2390 (0.08%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial sepsis
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Breast abscess
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	9 / 2390 (0.38%)	3 / 397 (0.76%)
occurrences causally related to treatment / all	0 / 9	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chest wall abscess
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Corona virus infection
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Coxsackie viral infection
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Croup infectious
subjects affected / exposed	3 / 2390 (0.13%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Eczema herpeticum
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	5 / 2390 (0.21%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	3 / 2390 (0.13%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Groin abscess
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hand-foot-and-mouth disease
subjects affected / exposed	2 / 2390 (0.08%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infection
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza
subjects affected / exposed	2 / 2390 (0.08%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Meningitis
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Otitis media
subjects affected / exposed	0 / 2390 (0.00%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Periorbital cellulitis
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	5 / 2390 (0.21%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural infection
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory tract infection viral
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	0 / 2390 (0.00%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	4 / 2390 (0.17%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 2390 (0.04%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Viral infection
subjects affected / exposed	3 / 2390 (0.13%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 2390 (0.00%)	2 / 397 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vulval abscess
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Failure to thrive
subjects affected / exposed	2 / 2390 (0.08%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Food intolerance
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dehydration
subjects affected / exposed	7 / 2390 (0.29%)	1 / 397 (0.25%)
occurrences causally related to treatment / all	0 / 7	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic ketoacidosis
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Type 1 diabetes mellitus
subjects affected / exposed	1 / 2390 (0.04%)	0 / 397 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	V419 (Combined Lots A, B, and C)	Control
Total subjects affected by non serious adverse events
subjects affected / exposed	2259 / 2390 (94.52%)	371 / 397 (93.45%)
Nervous system disorders
Somnolence
subjects affected / exposed	1816 / 2390 (75.98%)	298 / 397 (75.06%)
occurrences all number	4497	717
General disorders and administration site conditions
Crying
subjects affected / exposed	1867 / 2390 (78.12%)	300 / 397 (75.57%)
occurrences all number	4597	763
Irritability
subjects affected / exposed	1993 / 2390 (83.39%)	324 / 397 (81.61%)
occurrences all number	5595	925
Pyrexia
subjects affected / exposed	1285 / 2390 (53.77%)	174 / 397 (43.83%)
occurrences all number	2302	274
Injection site bruising
subjects affected / exposed	128 / 2390 (5.36%)	22 / 397 (5.54%)
occurrences all number	174	31
Injection site erythema
subjects affected / exposed	1302 / 2390 (54.48%)	203 / 397 (51.13%)
occurrences all number	5189	911
Injection site pain
subjects affected / exposed	1883 / 2390 (78.79%)	314 / 397 (79.09%)
occurrences all number	8854	1815
Injection site swelling
subjects affected / exposed	1073 / 2390 (44.90%)	166 / 397 (41.81%)
occurrences all number	3652	687
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	192 / 2390 (8.03%)	23 / 397 (5.79%)
occurrences all number	215	24
Vomiting
subjects affected / exposed	723 / 2390 (30.25%)	110 / 397 (27.71%)
occurrences all number	1139	171
Infections and infestations
Otitis media
subjects affected / exposed	147 / 2390 (6.15%)	39 / 397 (9.82%)
occurrences all number	162	44
Upper respiratory tract infection
subjects affected / exposed	276 / 2390 (11.55%)	48 / 397 (12.09%)
occurrences all number	306	54
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1355 / 2390 (56.69%)	217 / 397 (54.66%)
occurrences all number	2586	402

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

07 Mar 2011

Evaluation of lot consistency was revised to be based on GMTs, rather than response rates, at 1 month after the third dose of PR5I/Control, analysis of lot consistency based on response rates was moved from a conditional primary hypothesis to Secondary Hypothesis #1, a non-inferiority analysis of PR5I to Control was added as Secondary Hypothesis #3, statistical criterion for the evaluation of the immunogenicity of Prevnar13™ was revised, objectives and hypotheses were renumbered accordingly, sponsor name was updated to Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., all references to Interactive Voice Response System was updated to Interactive Response Technology, and the reference list was reorganized to present references sequentially.

24 Jan 2013

Added a new primary statistical analysis method for all GMT analyses to account for missing baseline titers due to limited serum volumes obtained from 2-month old infant subjects at study entry, added a second Per Protocol population (referred to as Per Protocol-Revised Window) in addition to the existing Per Protocol population (Per Protocol-Original Window) to account for subjects who received study vaccinations and/or blood draws outside of narrow protocol-defined visit windows, and added 2 sensitivity analyses: (1) analysis of GMT endpoints with no baseline adjustment and (2) analysis of GMT endpoints based on data from subjects with both baseline and post vaccination titers to support the ANCOVA with multiple imputation for missing baseline titers primary analysis for GMT endpoints.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Polyribosylribitol Phosphate (PRP) Antigen

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Polyribosylribitol Phosphate (PRP) Antigen

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Hepatitis B Surface Antigen

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Hepatitis B Surface Antigen

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Diphtheria Toxin

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Diphtheria Toxin

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Tetanus Toxin

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Tetanus Toxin

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Toxin

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Toxin

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Filamentous Hemagglutinin (FHA)

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Filamentous Hemagglutinin (FHA)

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Pertactin

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Pertactin

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Fimbriae

Primary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Fimbriae

Primary: Geometric Mean Titer (GMT) for Antibodies to Poliovirus Type 1

Primary: Geometric Mean Titer (GMT) for Antibodies to Poliovirus Type 1

Primary: Geometric Mean Titer (GMT) for Antibodies to Poliovirus Type 2

Primary: Geometric Mean Titer (GMT) for Antibodies to Poliovirus Type 2

Primary: Geometric Mean Titer (GMT) for Antibodies to Poliovirus Type 3

Primary: Geometric Mean Titer (GMT) for Antibodies to Poliovirus Type 3

Secondary: Percentage of Subjects Responding to Polyribosylribitol Phosphate (PRP) Antigen

Secondary: Percentage of Subjects Responding to Polyribosylribitol Phosphate (PRP) Antigen

Secondary: Percentage of Subjects Responding to Hepatitis B Surface Antigen

Secondary: Percentage of Subjects Responding to Hepatitis B Surface Antigen

Secondary: Percentage of Subjects Responding to Diphtheria Toxin

Secondary: Percentage of Subjects Responding to Diphtheria Toxin

Secondary: Percentage of Subjects Responding to Tetanus Toxin

Secondary: Percentage of Subjects Responding to Tetanus Toxin

Secondary: Percentage of Subjects Responding to Pertussis Toxin

Secondary: Percentage of Subjects Responding to Pertussis Toxin

Secondary: Percentage of Subjects Responding to Pertussis Filamentous Hemagglutinin (FHA)

Secondary: Percentage of Subjects Responding to Pertussis Filamentous Hemagglutinin (FHA)

Secondary: Percentage of Subjects Responding to Pertussis Pertactin (PRN)

Secondary: Percentage of Subjects Responding to Pertussis Pertactin (PRN)

Secondary: Percentage of Subjects Responding to Pertussis Fimbriae

Secondary: Percentage of Subjects Responding to Pertussis Fimbriae

Secondary: Percentage of Subjects Responding to Poliovirus Type 1

Secondary: Percentage of Subjects Responding to Poliovirus Type 1

Secondary: Percentage of Subjects Responding to Poliovirus Type 2

Secondary: Percentage of Subjects Responding to Poliovirus Type 2

Secondary: Percentage of Subjects Responding to Poliovirus Type 3

Secondary: Percentage of Subjects Responding to Poliovirus Type 3

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Toxin

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Toxin

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Filamentous Hemagglutinin (FHA)

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Filamentous Hemagglutinin (FHA)

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Pertactin

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Pertactin

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Fimbriae

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Fimbriae

Secondary: Percentage of Subjects Responding to Pertussis Toxin

Secondary: Percentage of Subjects Responding to Pertussis Toxin

Secondary: Percentage of Subjects Responding to Pertussis Filamentous Hemagglutinin (FHA)

Secondary: Percentage of Subjects Responding to Pertussis Filamentous Hemagglutinin (FHA)

Secondary: Percentage of Subjects Responding to Pertussis Pertactin (PRN)

Secondary: Percentage of Subjects Responding to Pertussis Pertactin (PRN)

Secondary: Percentage of Subjects Responding to Pertussis Fimbriae

Secondary: Percentage of Subjects Responding to Pertussis Fimbriae

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pneumococcal Serotypes

Secondary: Geometric Mean Concentrations (GMC) for Antibodies to Pneumococcal Serotypes

Secondary: Percentage of Subjects Reporting Solicited Injection-site and Systemic Reactions Within Five Days Following Any Infant Dose Vaccination in the V419 and Control Groups

Secondary: Percentage of Subjects Reporting Solicited Injection-site and Systemic Reactions Within Five Days Following Any Infant Dose Vaccination in the V419 and Control Groups

Secondary: Percentage of Subjects With Elevated Temperature By Severity Within Five Days Following Any Infant Dose Vaccination in the V419 and Control Groups

Secondary: Percentage of Subjects With Elevated Temperature By Severity Within Five Days Following Any Infant Dose Vaccination in the V419 and Control Groups

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)