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    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

    Close Top of page
    Trial identification
    Sponsor protocol code
    V419-006
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01340937
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Merck Sharp and Dohme Corp., A Subsidiary of Merck & Co., Inc.
    Sponsor organisation address
    2000 Galloping Hill Rd, Kenilworth, United States, 07033
    Public contact
    VP, Late Stage Development, Merck Sharp and Dohme Corp., A Subsidiary of Merck & Co., Inc., 800 672-6372, 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
    Paediatric regulatory details
    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?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 Jul 2013
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Jul 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the consistency of the Postdose 3 immune response to three manufactured lots of PR5I when given at 2, 4, and 6 months of age with respect to geometric mean concentrations (GMCs) and geometric mean titers (GMTs).
    Protection of trial subjects
    Only subjects that met all the study inclusion and none of the exclusion criteria were randomized and vaccinated in the study. Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment was also available on site in case of any immediate allergic reactions.
    Background therapy
    Not applicable
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    11 May 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 2808
    Worldwide total number of subjects
    2808
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    2808
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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

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

    Period 1
    Period 1 title
    Infant Series
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    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).

    Arms
    Are arms mutually exclusive
    Yes

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

    Investigational medicinal product name
    PR5I
    Investigational medicinal product code
    V419
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    PENTACEL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection at 15 months of age.

    Investigational medicinal product name
    RotaTeq™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    2 mL, oral, 1 dose each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Prevnar13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

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

    Investigational medicinal product name
    PR5I
    Investigational medicinal product code
    V419
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    PENTACEL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection at 15 months of age.

    Investigational medicinal product name
    RotaTeq™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    2 mL, oral, 1 dose each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Prevnar13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

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

    Investigational medicinal product name
    PR5I
    Investigational medicinal product code
    V419
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    PENTACEL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection at 15 months of age.

    Investigational medicinal product name
    RotaTeq™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    2 mL, oral, 1 dose each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Prevnar13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

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

    Investigational medicinal product name
    PENTACEL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

    Investigational medicinal product name
    RotaTeq™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    2 mL, oral, 1 dose each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Prevnar13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

    Investigational medicinal product name
    RECOMBIVAX HB™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2 and 6 months of age.

    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
         Other protocol criterion not met
             -
             1
             1
             -
         Death
             2
             -
             2
             -
         Protocol deviation
             1
             4
             4
             3
         Physician decision
             2
             3
             1
             -
         Randomized but not vaccinated
             -
             5
             2
             1
         Adverse event, non-fatal
             -
             1
             4
             -
         Consent withdrawn by subject
             33
             32
             30
             15
         Lost to follow-up
             20
             14
             12
             13
    Period 2
    Period 2 title
    Interim Period
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Data analyst, 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).

    Arms
    Are arms mutually exclusive
    Yes

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

    Investigational medicinal product name
    PR5I
    Investigational medicinal product code
    V419
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    PENTACEL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection at 15 months of age.

    Investigational medicinal product name
    RotaTeq™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    2 mL, oral, 1 dose each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Prevnar13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

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

    Investigational medicinal product name
    PR5I
    Investigational medicinal product code
    V419
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Prevnar13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

    Investigational medicinal product name
    RotaTeq™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    2 mL, oral, 1 dose each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    PENTACEL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection at 15 months of age.

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

    Investigational medicinal product name
    PR5I
    Investigational medicinal product code
    V419
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    RotaTeq™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    2 mL, oral, 1 dose each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Prevnar13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

    Investigational medicinal product name
    PENTACEL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection at 15 months of age.

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

    Investigational medicinal product name
    PENTACEL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

    Investigational medicinal product name
    Prevnar13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

    Investigational medicinal product name
    RECOMBIVAX HB™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2 and 6 months of age.

    Investigational medicinal product name
    RotaTeq™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    2 mL, oral, 1 dose each at 2, 4, and 6 months of age.

    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
         Protocol deviation
             5
             3
             6
             3
         Physician decision
             -
             1
             1
             -
         Other technical problems
             4
             4
             6
             3
         Adverse event, non-fatal
             1
             -
             1
             -
         Consent withdrawn by subject
             28
             23
             17
             12
         Lost to follow-up
             29
             48
             53
             23
    Period 3
    Period 3 title
    Toddler Vaccinations
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Data analyst, 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).

    Arms
    Are arms mutually exclusive
    Yes

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

    Investigational medicinal product name
    PR5I
    Investigational medicinal product code
    V419
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    PENTACEL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection at 15 months of age.

    Investigational medicinal product name
    RotaTeq™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    2 mL, oral, 1 dose each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Prevnar13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

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

    Investigational medicinal product name
    PR5I
    Investigational medicinal product code
    V419
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Prevnar13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

    Investigational medicinal product name
    RotaTeq™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    2 mL, oral, 1 dose each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    PENTACEL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection at 15 months of age.

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

    Investigational medicinal product name
    PR5I
    Investigational medicinal product code
    V419
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    RotaTeq™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    2 mL, oral, 1 dose each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Prevnar13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

    Investigational medicinal product name
    PENTACEL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection at 15 months of age.

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

    Investigational medicinal product name
    PENTACEL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

    Investigational medicinal product name
    RotaTeq™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    2 mL, oral, 1 dose each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Prevnar13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

    Investigational medicinal product name
    RECOMBIVAX HB™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2 and 6 months of age.

    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
         Protocol deviation
             -
             -
             -
             1
         Other technical problems
             1
             1
             1
             -
         Consent withdrawn by subject
             2
             2
             1
             1
         Lost to follow-up
             6
             14
             7
             8
    Period 4
    Period 4 title
    Combined Lots
    Is this the baseline period?
    No
    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.

    Arms
    Are arms mutually exclusive
    No

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

    Investigational medicinal product name
    PR5I
    Investigational medicinal product code
    V419
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Prevnar13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

    Investigational medicinal product name
    RotaTeq™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    2 mL, oral, 1 dose each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    PENTACEL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection at 15 months of age.

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

    Investigational medicinal product name
    PENTACEL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

    Investigational medicinal product name
    RECOMBIVAX HB™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2 and 6 months of age.

    Investigational medicinal product name
    Prevnar13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, 1 injection each at 2, 4, 6, and 15 months of age.

    Investigational medicinal product name
    RotaTeq™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    2 mL, oral, 1 dose each at 2, 4, and 6 months of age.

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

    Baseline characteristics

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

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

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

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

    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

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

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

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

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

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

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

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

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

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

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

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

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

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    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)
    Statistical analysis title
    Lot A/Lot B Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot B ratio.
    Comparison groups
    V419 Lot A v V419 Lot B
    Number of subjects included in analysis
    1200
    Analysis specification
    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).
    Statistical analysis title
    Lot A/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot C ratio.
    Comparison groups
    V419 Lot A v V419 Lot C
    Number of subjects included in analysis
    1199
    Analysis specification
    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).
    Statistical analysis title
    Lot B/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot B/Lot C ratio.
    Comparison groups
    V419 Lot B v V419 Lot C
    Number of subjects included in analysis
    1191
    Analysis specification
    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).
    Statistical analysis title
    Combined Lots A, B, and C/Control Ratio
    Statistical analysis description
    GMC ratio (Combined Lots A, B, and C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    2083
    Analysis specification
    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

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    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)
    Statistical analysis title
    Lot A/Lot B Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot B ratio.
    Comparison groups
    V419 Lot A v V419 Lot B
    Number of subjects included in analysis
    1187
    Analysis specification
    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).
    Statistical analysis title
    Lot A/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot C ratio.
    Comparison groups
    V419 Lot A v V419 Lot C
    Number of subjects included in analysis
    1168
    Analysis specification
    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).
    Statistical analysis title
    Lot B/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot B/Lot C ratio.
    Comparison groups
    V419 Lot B v V419 Lot C
    Number of subjects included in analysis
    1179
    Analysis specification
    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

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    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)
    Statistical analysis title
    Lot A/Lot B Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot B ratio.
    Comparison groups
    V419 Lot A v V419 Lot B
    Number of subjects included in analysis
    1247
    Analysis specification
    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).
    Statistical analysis title
    Lot A/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot C ratio.
    Comparison groups
    V419 Lot A v V419 Lot C
    Number of subjects included in analysis
    1240
    Analysis specification
    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).
    Statistical analysis title
    Lot B/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot B/Lot C ratio.
    Comparison groups
    V419 Lot B v V419 Lot C
    Number of subjects included in analysis
    1243
    Analysis specification
    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

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    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)
    Statistical analysis title
    Lot A/Lot B Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot B ratio.
    Comparison groups
    V419 Lot A v V419 Lot B
    Number of subjects included in analysis
    1231
    Analysis specification
    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).
    Statistical analysis title
    Lot A/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot C ratio.
    Comparison groups
    V419 Lot A v V419 Lot C
    Number of subjects included in analysis
    1234
    Analysis specification
    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).
    Statistical analysis title
    Lot B/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot B/Lot C ratio.
    Comparison groups
    V419 Lot B v V419 Lot C
    Number of subjects included in analysis
    1221
    Analysis specification
    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

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    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)
    Statistical analysis title
    Lot A/Lot B Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot B ratio.
    Comparison groups
    V419 Lot A v V419 Lot B
    Number of subjects included in analysis
    1281
    Analysis specification
    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).
    Statistical analysis title
    Lot A/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot C ratio.
    Comparison groups
    V419 Lot A v V419 Lot C
    Number of subjects included in analysis
    1269
    Analysis specification
    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).
    Statistical analysis title
    Lot B/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot B/Lot C ratio.
    Comparison groups
    V419 Lot B v V419 Lot C
    Number of subjects included in analysis
    1256
    Analysis specification
    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).
    Statistical analysis title
    Combined Lots A, B, and C/Control Ratio
    Statistical analysis description
    GMC ratio (Combined Lots A, B, and C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    2212
    Analysis specification
    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)

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    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)
    Statistical analysis title
    Lot A/Lot B Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot B ratio.
    Comparison groups
    V419 Lot B v V419 Lot A
    Number of subjects included in analysis
    1275
    Analysis specification
    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).
    Statistical analysis title
    Lot A/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot C ratio.
    Comparison groups
    V419 Lot A v V419 Lot C
    Number of subjects included in analysis
    1272
    Analysis specification
    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).
    Statistical analysis title
    Lot B/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot B/Lot C ratio.
    Comparison groups
    V419 Lot B v V419 Lot C
    Number of subjects included in analysis
    1259
    Analysis specification
    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).
    Statistical analysis title
    Combined Lots A, B, and C/Control Ratio
    Statistical analysis description
    GMC ratio (Combined Lots A, B, and C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    2215
    Analysis specification
    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

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    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)
    Statistical analysis title
    Lot A/Lot B Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot B ratio.
    Comparison groups
    V419 Lot A v V419 Lot B
    Number of subjects included in analysis
    1248
    Analysis specification
    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).
    Statistical analysis title
    Lot A/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot C ratio.
    Comparison groups
    V419 Lot A v V419 Lot C
    Number of subjects included in analysis
    1243
    Analysis specification
    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).
    Statistical analysis title
    Lot B/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot B/Lot C ratio.
    Comparison groups
    V419 Lot B v V419 Lot C
    Number of subjects included in analysis
    1227
    Analysis specification
    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).
    Statistical analysis title
    Combined Lots A, B, and C/Control Ratio
    Statistical analysis description
    GMC ratio (Combined Lots A, B, and C/Control)
    Comparison groups
    Combined Lot A, B, and C v Control
    Number of subjects included in analysis
    2162
    Analysis specification
    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

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    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)
    Statistical analysis title
    Lot A/Lot B Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot B ratio.
    Comparison groups
    V419 Lot A v V419 Lot B
    Number of subjects included in analysis
    1273
    Analysis specification
    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).
    Statistical analysis title
    Lot A/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot A/Lot C ratio.
    Comparison groups
    V419 Lot A v V419 Lot C
    Number of subjects included in analysis
    1264
    Analysis specification
    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).
    Statistical analysis title
    Lot B/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMC of Lot B/Lot C ratio.
    Comparison groups
    V419 Lot B v V419 Lot C
    Number of subjects included in analysis
    1255
    Analysis specification
    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).
    Statistical analysis title
    Combined Lots A, B, and C/Control Ratio
    Statistical analysis description
    GMC ratio (Combined Lots A, B, and C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    2205
    Analysis specification
    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

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    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)
    Statistical analysis title
    Lot A/Lot B Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMT of Lot A/Lot B ratio.
    Comparison groups
    V419 Lot A v V419 Lot B
    Number of subjects included in analysis
    1262
    Analysis specification
    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).
    Statistical analysis title
    Lot A/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMT of Lot A/Lot C ratio.
    Comparison groups
    V419 Lot A v V419 Lot C
    Number of subjects included in analysis
    1258
    Analysis specification
    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).
    Statistical analysis title
    Lot B/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMT of Lot B/Lot C ratio.
    Comparison groups
    V419 Lot B v V419 Lot C
    Number of subjects included in analysis
    1260
    Analysis specification
    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

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    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)
    Statistical analysis title
    Lot A/Lot B Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMT of Lot A/Lot B ratio.
    Comparison groups
    V419 Lot A v V419 Lot B
    Number of subjects included in analysis
    1262
    Analysis specification
    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).
    Statistical analysis title
    Lot B/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMT of Lot B/Lot C ratio.
    Comparison groups
    V419 Lot B v V419 Lot C
    Number of subjects included in analysis
    1265
    Analysis specification
    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).
    Statistical analysis title
    Lot A/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMT of Lot A/Lot C ratio.
    Comparison groups
    V419 Lot A v V419 Lot C
    Number of subjects included in analysis
    1263
    Analysis specification
    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

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    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)
    Statistical analysis title
    Lot A/Lot B Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMT of Lot A/Lot B ratio.
    Comparison groups
    V419 Lot A v V419 Lot B
    Number of subjects included in analysis
    1249
    Analysis specification
    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).
    Statistical analysis title
    Lot B/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMT of Lot B/Lot C ratio.
    Comparison groups
    V419 Lot B v V419 Lot C
    Number of subjects included in analysis
    1250
    Analysis specification
    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).
    Statistical analysis title
    Lot A/Lot C Ratio
    Statistical analysis description
    Lot consistency analysis regarding GMT of Lot A/Lot C ratio.
    Comparison groups
    V419 Lot C v V419 Lot A
    Number of subjects included in analysis
    1249
    Analysis specification
    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

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    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)
    Statistical analysis title
    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%).
    Statistical analysis title
    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%).
    Statistical analysis title
    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%).
    Statistical analysis title
    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%.
    Statistical analysis title
    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

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    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)
    Statistical analysis title
    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%).
    Statistical analysis title
    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%).
    Statistical analysis title
    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
    0
    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%).
    Statistical analysis title
    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

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    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)
    Statistical analysis title
    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%).
    Statistical analysis title
    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%).
    Statistical analysis title
    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%).
    Statistical analysis title
    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

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    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)
    Statistical analysis title
    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%).
    Statistical analysis title
    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%).
    Statistical analysis title
    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
    0
    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%).
    Statistical analysis title
    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

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    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)
    Statistical analysis title
    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%).
    Statistical analysis title
    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%).
    Statistical analysis title
    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%).
    Statistical analysis title
    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)

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    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)
    Statistical analysis title
    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%).
    Statistical analysis title
    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%).
    Statistical analysis title
    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%).
    Statistical analysis title
    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)

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    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)
    Statistical analysis title
    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%).
    Statistical analysis title
    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%).
    Statistical analysis title
    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%).
    Statistical analysis title
    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

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    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)
    Statistical analysis title
    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%).
    Statistical analysis title
    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%).
    Statistical analysis title
    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%).
    Statistical analysis title
    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

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    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)
    Statistical analysis title
    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
    0
    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%).
    Statistical analysis title
    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
    0
    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%).
    Statistical analysis title
    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
    0
    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%).
    Statistical analysis title
    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

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    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)
    Statistical analysis title
    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
    0
    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%).
    Statistical analysis title
    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
    0
    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%).
    Statistical analysis title
    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
    0
    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%).
    Statistical analysis title
    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
    0
    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

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    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)
    Statistical analysis title
    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
    0
    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%).
    Statistical analysis title
    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
    0
    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%).
    Statistical analysis title
    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
    0
    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%).
    Statistical analysis title
    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

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    End point title
    Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Toxin
    End point description
    Subject serum samples were collected for testing with an ELISA for antibodies to pertussis toxin. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 4.
    End point type
    Secondary
    End point timeframe
    Postdose 4 (Month 16)
    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)
    Statistical analysis title
    Combined Lots A, B, and C/Control Ratio
    Statistical analysis description
    GMC ratio (Combined Lots A, B, and C/Control)
    Comparison groups
    Combined Lot A, B, and C v Control
    Number of subjects included in analysis
    2015
    Analysis specification
    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)

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    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)
    Statistical analysis title
    Combined Lots A, B, and C/Control Ratio
    Statistical analysis description
    GMC ratio (Combined Lots A, B, and C/Control)
    Comparison groups
    Combined Lot A, B, and C v Control
    Number of subjects included in analysis
    2013
    Analysis specification
    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

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    End point title
    Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Pertactin
    End point description
    Subject serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 4.
    End point type
    Secondary
    End point timeframe
    Postdose 4 (Month 16)
    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)
    Statistical analysis title
    Combined Lots A, B, and C/Control Ratio
    Statistical analysis description
    GMC ratio (Combined Lots A, B, and C/Control)
    Comparison groups
    Combined Lot A, B, and C v Control
    Number of subjects included in analysis
    2017
    Analysis specification
    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

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    End point title
    Geometric Mean Concentrations (GMC) for Antibodies to Pertussis Fimbriae
    End point description
    Subject serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. The analysis population included subjects who met the inclusion criteria, were not protocol violators, had an infant vaccination window of 42 to 84 days after the previous dose, and a blood draw sample window for the endpoint of 28 to 51 days after dose 4.
    End point type
    Secondary
    End point timeframe
    Postdose 4 (Month 16)
    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)
    Statistical analysis title
    Combined Lots A, B, and C/Control Ratio
    Statistical analysis description
    GMC ratio (Combined Lots A, B, and C/Control)
    Comparison groups
    Combined Lot A, B, and C v Control
    Number of subjects included in analysis
    2017
    Analysis specification
    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

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    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)
    Statistical analysis title
    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)

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    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)
    Statistical analysis title
    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)

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    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)
    Statistical analysis title
    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

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    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)
    Statistical analysis title
    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
    3
    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

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    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)
    Statistical analysis title
    Combined Lots A, B, C/Control Ratio; Serotype 1
    Statistical analysis description
    GMC ratio (Combined Lots A, B, C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    1447
    Analysis specification
    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.
    Statistical analysis title
    Combined Lots A, B, C/Control Ratio; Serotype 3
    Statistical analysis description
    GMC ratio (Combined Lots A, B, C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    1447
    Analysis specification
    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.
    Statistical analysis title
    Combined Lots A, B, C/Control Ratio; Serotype 4
    Statistical analysis description
    GMC ratio (Combined Lots A, B, C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    1447
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [95]
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    GMC Ratio
    Point estimate
    1
    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.
    Statistical analysis title
    Combined Lots A, B, C/Control Ratio; Serotype 5
    Statistical analysis description
    GMC ratio (Combined Lots A, B, C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    1447
    Analysis specification
    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.
    Statistical analysis title
    Combined Lots A, B, C/Control Ratio; Serotype 6A
    Statistical analysis description
    GMC ratio (Combined Lots A, B, C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    1447
    Analysis specification
    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.
    Statistical analysis title
    Combined Lots A, B, C/Control Ratio; Serotype 6B
    Statistical analysis description
    GMC ratio (Combined Lots A, B, C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    1447
    Analysis specification
    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.
    Statistical analysis title
    Combined Lots A, B, C/Control Ratio; Serotype 7F
    Statistical analysis description
    GMC ratio (Combined Lots A, B, C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    1447
    Analysis specification
    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.
    Statistical analysis title
    Combined Lots A, B, C/Control Ratio; Serotype 9V
    Statistical analysis description
    GMC ratio (Combined Lots A, B, C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    1447
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [100]
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    GMC Ratio
    Point estimate
    1
    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.
    Statistical analysis title
    Combined Lots A, B, C/Control Ratio; Serotype 14
    Statistical analysis description
    GMC ratio (Combined Lots A, B, C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    1447
    Analysis specification
    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.
    Statistical analysis title
    Combined Lots A, B, C/Control Ratio; Serotype 18C
    Statistical analysis description
    GMC ratio (Combined Lots A, B, C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    1447
    Analysis specification
    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
    1
    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.
    Statistical analysis title
    Combined Lots A, B, C/Control Ratio; Serotype 19A
    Statistical analysis description
    GMC ratio (Combined Lots A, B, C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    1447
    Analysis specification
    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.
    Statistical analysis title
    Combined Lots A, B, C/Control Ratio; Serotype 19F
    Statistical analysis description
    GMC ratio (Combined Lots A, B, C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    1447
    Analysis specification
    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.
    Statistical analysis title
    Combined Lots A, B, C/Control Ratio; Serotype 23F
    Statistical analysis description
    GMC ratio (Combined Lots A, B, C/Control)
    Comparison groups
    Control v Combined Lot A, B, and C
    Number of subjects included in analysis
    1447
    Analysis specification
    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

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    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

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    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
    Statistical analysis title
    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.
    Statistical analysis title
    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.
    Statistical analysis title
    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.
    Statistical analysis title
    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.
    Statistical analysis title
    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.
    Statistical analysis title
    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.
    Statistical analysis title
    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.
    Statistical analysis title
    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

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    Adverse events information
    Timeframe for reporting adverse events
    SAEs: up to 6 months after vaccination 3 (the last infant vaccination) and up to 15 days after vaccination 4 (the toddler vaccination); 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 used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    V419 (Combined Lots A, B, and C)
    Reporting group description
    V419 (Combined Lots A, B, and C) 0.5 mL intramuscular injection (IM) at 2, 4, 6 months of age; Pentacel™ 0.5 mL IM at 15 months of age; Prevnar13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.

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

    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
    Respiratory, thoracic and mediastinal disorders
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    Metabolism and nutrition disorders
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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