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    Clinical Trial Results:
    A Phase 3, Open-Label, Randomized, Parallel-Group, Multi-Center Study to Evaluate the Safety and Immunogenicity of Novartis Meningococcal ACWY Conjugate Vaccine When Administered with Routine Infant Vaccinations to Healthy Infants.

    Due to a system error, the data reported in v1 is not correct and has been removed from public view.
    Summary
    EudraCT number
    		 2014-004605-33
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    13 Nov 2009

    Results information
    Results version number
    		 v2(current)
    This version publication date
    04 Jun 2016
    First version publication date
    31 Jan 2015
    Other versions
    		 v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    re-QC study needed because of EudraCT system glitch and updates to results are required.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    V59P14
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00474526
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Vaccines and Diagnostics, Inc
    Sponsor organisation address
    350 Massachusetts Ave, Cambridge, United States, 02139
    Public contact
    Posting Director, Novartis Vaccines, RegistryContactVaccinesUS@novartis.com
    Scientific contact
    Posting Director, Novartis Vaccines, RegistryContactVaccinesUS@novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000032-PIP01-07
    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
    19 Aug 2010
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Nov 2009
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Immunogenicity against Neisseria meningitidis serogroups A, C, W and Y; after four doses of MenACWY-CRM at 2, 4, and 6 and 12 months of age.
    Protection of trial subjects
    This trial was performed with the ethical principles that have their origin in the Declaration of Helsinki, that are consistent with Good Clinical Practice (GCP) according to International Conference on Harmonisation (ICH) guidelines.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Mar 2007
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 1530
    Country: Number of subjects enrolled
    Colombia: 1507
    Country: Number of subjects enrolled
    United States: 1508
    Worldwide total number of subjects
    4545
    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)
    4545
    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
    		 All enrolled subjects were included in the study

    Pre-assignment
    Screening details
    		 Approximately 4500 infants 2 months of age (55 – 89 days inclusive) were planned to be enrolled and randomized open-label to treatment in a 2:1 ratio, (MenACWY + routine infant vaccines: routine infant vaccines only), stratified by study site, and geographic region (also in a 2:1 ratio, Latin America: US).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 US1A (MenACWY-CRM + Infant Vaccines)
    Arm description
    		 US infants received MenACWY at 2, 4 and 6 months of age along with routine infant vaccines, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccine. These infants received a fourth dose of MenACWY concomitantly with pneumococcal, HAV, and MMR-V vaccines at 12 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 US1B (MenACWY-CRM + Infant Vaccines)
    Arm description
    		 US infants received MenACWY at 2, 4 and 6 months of age along with routine infant vaccines, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines. These infants received pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and a fourth dose of MenACWY at 13 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 US2 (Infant Vaccines Only)
    Arm description
    		 US infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These infants received one dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and a second dose of MenACWY at 15 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 US3 (MenACWY-CRM + Infant Vaccines)
    Arm description
    		 US infants received MenACWY at 2, 4 and 6 months of age along with routine infant vaccines, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccine. These infants received fourth dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 US4A (Infant Vaccines Only)
    Arm description
    		 US infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These infants received one dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and a second dose of MenACWY at 15 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 US4B (Infant Vaccines Only)
    Arm description
    		 US infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These subjects received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and one dose of MenACWY at 13 and a second dose of MenACWY at 15 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 US4C (Infant Vaccines Only)
    Arm description
    		 US infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines, at 2, 4 and 6 months of age. These subjects received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months and one dose of MenACWY at 18 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 LA1A (MenACWY-CRM + Infant Vaccines)
    Arm description
    		 Latin American LA infants received MenACWY at 2 and 6 months of age; and as part of routine infant vaccination schedule, received, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These subjects received a third dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 LA1B (MenACWY-CRM + Infant Vaccines)
    Arm description
    		 LA infants received MenACWY at 2 and 6 months of age and as part of routine infant vaccination schedule, received, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These subjects received pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months and a third dose of MenACWY at 13 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 LA2 (Infant Vaccines Only)
    Arm description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These infants received one dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and a second dose of MenACWY at 15 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 LA3A (MenACWY-CRM + Infant Vaccines)
    Arm description
    		 LA infants received MenACWY at 2, 4 and 6 months of age; and as part of routine infant vaccination schedule received, DTaP-IPV-HBV, Hib, pneumococcal conjugate vaccine, and rotavirus vaccine. Around 12 months of age, these infants were recommended to receive pneumococcal conjugate vaccine, HAV, and MMR-V. At 16 months of age, these subjects received the fourth dose of MenACWY along with concomitant DTaP and Hib.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 LA3B (MenACWY-CRM + Infant Vaccines)
    Arm description
    		 LA infants received MenACWY at 2, 4 and 6 months of age; and as part of routine infant vaccination schedule received, DTaP-IPV-HBV, Hib, pneumococcal conjugate vaccine, and rotavirus vaccine. Around 12 months of age, received pneumococcal conjugate vaccine, HAV, and MMR-V. At 16 months of age, these subjects received DTaP and Hib. At 17 months of age, these subjects received the fourth dose of MenACWY.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 LA4 (Infant Vaccines Only)
    Arm description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, pneumococcal conjugate vaccine, and rotavirus vaccine at 2, 4 and 6 months of age. These infants received one dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months and a second dose of MenACWY along with DTaP and Hib vaccines at 15 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 LA5 (MenACWY-CRM + Infant Vaccines)
    Arm description
    		 LA infants received MenACWY at 2, 4 and 6 months of age,; and as part of routine infant vaccination schedule received, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines. At 12 months of age, these subjects received the fourth dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 LA6A (Infant Vaccines Only)
    Arm description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus, and pneumococcal conjugate vaccines, at 2, 4 and 6 months of age. These infants received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and one dose of MenACWY at 12 and a second dose of MenACWY at 15 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 LA6B (Infant Vaccines Only)
    Arm description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus, and pneumococcal conjugate vaccines, at 2, 4 and 6 months of age. These infants received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and one dose of MenACWY at 13 and a second dose of MenACWY at 15 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 LA6C (Infant Vaccines Only)
    Arm description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus, and pneumococcal conjugate vaccines, at 2, 4 and 6 months of age. These infants received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and one dose of MenACWY at 18 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 and Routine Vaccines
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 ml of MenACWY IM injection in the anterolateral area of the right thigh. Routine vaccines were administered to subjects according to manufacturer instructions.

    Number of subjects in period 1
    		US1A (MenACWY-CRM + Infant Vaccines) US1B (MenACWY-CRM + Infant Vaccines) US2 (Infant Vaccines Only) US3 (MenACWY-CRM + Infant Vaccines) US4A (Infant Vaccines Only) US4B (Infant Vaccines Only) US4C (Infant Vaccines Only) LA1A (MenACWY-CRM + Infant Vaccines) LA1B (MenACWY-CRM + Infant Vaccines) LA2 (Infant Vaccines Only) LA3A (MenACWY-CRM + Infant Vaccines) LA3B (MenACWY-CRM + Infant Vaccines) LA4 (Infant Vaccines Only) LA5 (MenACWY-CRM + Infant Vaccines) LA6A (Infant Vaccines Only) LA6B (Infant Vaccines Only) LA6C (Infant Vaccines Only)
    Started
    154
    166
    159
    680
    76
    70
    203
    151
    150
    148
    151
    150
    150
    1426
    358
    170
    183
    Completed
    121
    120
    110
    561
    8
    54
    178
    145
    144
    121
    141
    139
    135
    1270
    281
    152
    174
    Not completed
    33
    46
    49
    119
    68
    16
    25
    6
    6
    27
    10
    11
    15
    156
    77
    18
    9
         Adverse event, non-fatal
    2
    -
    2
    4
    2
    1
    1
    -
    -
    -
    -
    -
    -
    -
    1
    1
    -
         Death
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    3
    -
    -
    -
         Inappropriate enrollment
    -
    1
    -
    1
    2
    -
    -
    -
    -
    -
    -
    -
    -
    2
    2
    -
    -
         Unable to classify
    1
    -
    -
    1
    3
    2
    -
    1
    -
    3
    -
    -
    -
    20
    12
    6
    1
         Withdrawal by Subject
    9
    24
    21
    52
    38
    6
    12
    4
    4
    13
    5
    4
    4
    37
    22
    1
    1
         Lost to follow-up
    8
    6
    13
    29
    11
    5
    8
    1
    -
    6
    2
    4
    6
    74
    29
    4
    5
         Administrative reason
    11
    9
    9
    20
    9
    1
    1
    -
    2
    1
    1
    1
    1
    1
    2
    -
    -
         Protocol deviation
    2
    6
    4
    12
    3
    1
    3
    -
    -
    4
    2
    2
    4
    19
    9
    6
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    US1A (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 US infants received MenACWY at 2, 4 and 6 months of age along with routine infant vaccines, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccine. These infants received a fourth dose of MenACWY concomitantly with pneumococcal, HAV, and MMR-V vaccines at 12 months of age.

    Reporting group title
    US1B (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 US infants received MenACWY at 2, 4 and 6 months of age along with routine infant vaccines, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines. These infants received pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and a fourth dose of MenACWY at 13 months of age.

    Reporting group title
    US2 (Infant Vaccines Only)
    Reporting group description
    		 US infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These infants received one dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and a second dose of MenACWY at 15 months of age.

    Reporting group title
    US3 (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 US infants received MenACWY at 2, 4 and 6 months of age along with routine infant vaccines, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccine. These infants received fourth dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months of age.

    Reporting group title
    US4A (Infant Vaccines Only)
    Reporting group description
    		 US infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These infants received one dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and a second dose of MenACWY at 15 months of age.

    Reporting group title
    US4B (Infant Vaccines Only)
    Reporting group description
    		 US infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These subjects received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and one dose of MenACWY at 13 and a second dose of MenACWY at 15 months of age.

    Reporting group title
    US4C (Infant Vaccines Only)
    Reporting group description
    		 US infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines, at 2, 4 and 6 months of age. These subjects received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months and one dose of MenACWY at 18 months of age.

    Reporting group title
    LA1A (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 Latin American LA infants received MenACWY at 2 and 6 months of age; and as part of routine infant vaccination schedule, received, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These subjects received a third dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months of age.

    Reporting group title
    LA1B (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 LA infants received MenACWY at 2 and 6 months of age and as part of routine infant vaccination schedule, received, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These subjects received pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months and a third dose of MenACWY at 13 months of age.

    Reporting group title
    LA2 (Infant Vaccines Only)
    Reporting group description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These infants received one dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and a second dose of MenACWY at 15 months of age.

    Reporting group title
    LA3A (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 LA infants received MenACWY at 2, 4 and 6 months of age; and as part of routine infant vaccination schedule received, DTaP-IPV-HBV, Hib, pneumococcal conjugate vaccine, and rotavirus vaccine. Around 12 months of age, these infants were recommended to receive pneumococcal conjugate vaccine, HAV, and MMR-V. At 16 months of age, these subjects received the fourth dose of MenACWY along with concomitant DTaP and Hib.

    Reporting group title
    LA3B (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 LA infants received MenACWY at 2, 4 and 6 months of age; and as part of routine infant vaccination schedule received, DTaP-IPV-HBV, Hib, pneumococcal conjugate vaccine, and rotavirus vaccine. Around 12 months of age, received pneumococcal conjugate vaccine, HAV, and MMR-V. At 16 months of age, these subjects received DTaP and Hib. At 17 months of age, these subjects received the fourth dose of MenACWY.

    Reporting group title
    LA4 (Infant Vaccines Only)
    Reporting group description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, pneumococcal conjugate vaccine, and rotavirus vaccine at 2, 4 and 6 months of age. These infants received one dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months and a second dose of MenACWY along with DTaP and Hib vaccines at 15 months of age.

    Reporting group title
    LA5 (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 LA infants received MenACWY at 2, 4 and 6 months of age,; and as part of routine infant vaccination schedule received, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines. At 12 months of age, these subjects received the fourth dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V.

    Reporting group title
    LA6A (Infant Vaccines Only)
    Reporting group description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus, and pneumococcal conjugate vaccines, at 2, 4 and 6 months of age. These infants received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and one dose of MenACWY at 12 and a second dose of MenACWY at 15 months of age.

    Reporting group title
    LA6B (Infant Vaccines Only)
    Reporting group description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus, and pneumococcal conjugate vaccines, at 2, 4 and 6 months of age. These infants received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and one dose of MenACWY at 13 and a second dose of MenACWY at 15 months of age.

    Reporting group title
    LA6C (Infant Vaccines Only)
    Reporting group description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus, and pneumococcal conjugate vaccines, at 2, 4 and 6 months of age. These infants received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and one dose of MenACWY at 18 months of age.

    Reporting group values
    		 US1A (MenACWY-CRM + Infant Vaccines) US1B (MenACWY-CRM + Infant Vaccines) US2 (Infant Vaccines Only) US3 (MenACWY-CRM + Infant Vaccines) US4A (Infant Vaccines Only) US4B (Infant Vaccines Only) US4C (Infant Vaccines Only) LA1A (MenACWY-CRM + Infant Vaccines) LA1B (MenACWY-CRM + Infant Vaccines) LA2 (Infant Vaccines Only) LA3A (MenACWY-CRM + Infant Vaccines) LA3B (MenACWY-CRM + Infant Vaccines) LA4 (Infant Vaccines Only) LA5 (MenACWY-CRM + Infant Vaccines) LA6A (Infant Vaccines Only) LA6B (Infant Vaccines Only) LA6C (Infant Vaccines Only) Total
    Number of subjects
    		 154 166 159 680 76 70 203 151 150 148 151 150 150 1426 358 170 183 4545
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 154 166 159 680 76 70 203 151 150 148 151 150 150 1426 358 170 183 4545
        Children (2-11 years)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        From 65-84 years
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        85 years and over
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    Age continuous
    Units: days
        arithmetic mean (standard deviation)
    		 66.1 ( 7.2 ) 65.8 ( 6.6 ) 65.7 ( 6.5 ) 65 ( 6 ) 66.1 ( 6.2 ) 65 ( 6.5 ) 65.9 ( 6.5 ) 68 ( 7.7 ) 68.6 ( 8.9 ) 67.8 ( 8.3 ) 67.1 ( 7.9 ) 68.4 ( 8.7 ) 67.5 ( 8 ) 65 ( 9.4 ) 67.7 ( 9.7 ) 59.5 ( 6.2 ) 65 ( 7.9 ) -
    Gender categorical
    Units: Subjects
        Female
    		 68 72 71 340 39 29 103 79 82 72 72 75 81 682 178 89 91 2223
        Male
    		 86 94 88 340 37 41 100 72 68 76 79 75 69 744 180 81 92 2322

    End points

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    End points reporting groups
    Reporting group title
    US1A (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 US infants received MenACWY at 2, 4 and 6 months of age along with routine infant vaccines, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccine. These infants received a fourth dose of MenACWY concomitantly with pneumococcal, HAV, and MMR-V vaccines at 12 months of age.

    Reporting group title
    US1B (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 US infants received MenACWY at 2, 4 and 6 months of age along with routine infant vaccines, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines. These infants received pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and a fourth dose of MenACWY at 13 months of age.

    Reporting group title
    US2 (Infant Vaccines Only)
    Reporting group description
    		 US infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These infants received one dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and a second dose of MenACWY at 15 months of age.

    Reporting group title
    US3 (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 US infants received MenACWY at 2, 4 and 6 months of age along with routine infant vaccines, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccine. These infants received fourth dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months of age.

    Reporting group title
    US4A (Infant Vaccines Only)
    Reporting group description
    		 US infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These infants received one dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and a second dose of MenACWY at 15 months of age.

    Reporting group title
    US4B (Infant Vaccines Only)
    Reporting group description
    		 US infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These subjects received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and one dose of MenACWY at 13 and a second dose of MenACWY at 15 months of age.

    Reporting group title
    US4C (Infant Vaccines Only)
    Reporting group description
    		 US infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines, at 2, 4 and 6 months of age. These subjects received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months and one dose of MenACWY at 18 months of age.

    Reporting group title
    LA1A (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 Latin American LA infants received MenACWY at 2 and 6 months of age; and as part of routine infant vaccination schedule, received, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These subjects received a third dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months of age.

    Reporting group title
    LA1B (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 LA infants received MenACWY at 2 and 6 months of age and as part of routine infant vaccination schedule, received, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These subjects received pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months and a third dose of MenACWY at 13 months of age.

    Reporting group title
    LA2 (Infant Vaccines Only)
    Reporting group description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These infants received one dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and a second dose of MenACWY at 15 months of age.

    Reporting group title
    LA3A (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 LA infants received MenACWY at 2, 4 and 6 months of age; and as part of routine infant vaccination schedule received, DTaP-IPV-HBV, Hib, pneumococcal conjugate vaccine, and rotavirus vaccine. Around 12 months of age, these infants were recommended to receive pneumococcal conjugate vaccine, HAV, and MMR-V. At 16 months of age, these subjects received the fourth dose of MenACWY along with concomitant DTaP and Hib.

    Reporting group title
    LA3B (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 LA infants received MenACWY at 2, 4 and 6 months of age; and as part of routine infant vaccination schedule received, DTaP-IPV-HBV, Hib, pneumococcal conjugate vaccine, and rotavirus vaccine. Around 12 months of age, received pneumococcal conjugate vaccine, HAV, and MMR-V. At 16 months of age, these subjects received DTaP and Hib. At 17 months of age, these subjects received the fourth dose of MenACWY.

    Reporting group title
    LA4 (Infant Vaccines Only)
    Reporting group description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, pneumococcal conjugate vaccine, and rotavirus vaccine at 2, 4 and 6 months of age. These infants received one dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months and a second dose of MenACWY along with DTaP and Hib vaccines at 15 months of age.

    Reporting group title
    LA5 (MenACWY-CRM + Infant Vaccines)
    Reporting group description
    		 LA infants received MenACWY at 2, 4 and 6 months of age,; and as part of routine infant vaccination schedule received, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines. At 12 months of age, these subjects received the fourth dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V.

    Reporting group title
    LA6A (Infant Vaccines Only)
    Reporting group description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus, and pneumococcal conjugate vaccines, at 2, 4 and 6 months of age. These infants received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and one dose of MenACWY at 12 and a second dose of MenACWY at 15 months of age.

    Reporting group title
    LA6B (Infant Vaccines Only)
    Reporting group description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus, and pneumococcal conjugate vaccines, at 2, 4 and 6 months of age. These infants received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and one dose of MenACWY at 13 and a second dose of MenACWY at 15 months of age.

    Reporting group title
    LA6C (Infant Vaccines Only)
    Reporting group description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus, and pneumococcal conjugate vaccines, at 2, 4 and 6 months of age. These infants received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and one dose of MenACWY at 18 months of age.

    Subject analysis set title
    Exposed population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All enrolled subjects who actually received a study vaccination.

    Subject analysis set title
    Enrolled population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All subjects who signed an informed consent, underwent screening procedures, and were randomized

    Subject analysis set title
    Safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed population who provided post-baseline safety data.

    Subject analysis set title
    Concomitant Infant US subjects
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    US infant subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviations.

    Subject analysis set title
    MenACWY Infant US subjects
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    US infant subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviations.

    Subject analysis set title
    Pertussis Infant US subjects
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    US infant subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviations.

    Subject analysis set title
    MenACWY Infant LA subjects
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    LA infant subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviations.

    Subject analysis set title
    MenACWY Toddler US subjects
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    US toddler subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviations

    Subject analysis set title
    Pneumococcal Toddler US subjects
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    US toddler subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviations.

    Subject analysis set title
    Concomitant Infant LA subjects
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    LA infant subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviations.

    Subject analysis set title
    Pertussis Infant LA subjects
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    LA infant subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviations.

    Subject analysis set title
    MenACWY Toddler LA subjects
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    LA toddler subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviations.

    Subject analysis set title
    Concomitant Toddler LA subjects
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    LA toddler subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviations.

    Subject analysis set title
    Pertussis Toddler LA subjects
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    LA toddler subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviations.

    Subject analysis set title
    Pneumococcal Toddler LA subjects
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    LA toddler subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviations.

    Subject analysis set title
    US4B+US4C Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed US4B and US4C population who provided post-baseline safety data.

    Subject analysis set title
    US1A + US3 Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed US1A and US3 population who provided post-baseline safety data.

    Subject analysis set title
    US2+US4A Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed US2 and US4A population who provided post-baseline safety data.

    Subject analysis set title
    LA3 Per Protocol Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All LA3 subjects who received doses of vaccine correctly, and provided evaluable serum samples at the relevant time points.

    Subject analysis set title
    LA1 Per Protocol Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All LA1 subjects who received doses of vaccine correctly, and provided evaluable serum samples at the relevant time points.

    Subject analysis set title
    LA2+LA4+LA6A Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed LA2, LA4 and LA6A population who provided post-baseline safety data.

    Subject analysis set title
    LA6B+LA6C Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed LA6B and LA6C population who provided post-baseline safety data.

    Subject analysis set title
    US1 Per Protocol Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All US1 subjects who received doses of vaccine correctly, and provided evaluable serum samples at the relevant time points.

    Subject analysis set title
    US4 Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed US4 population who provided post-baseline safety data.

    Subject analysis set title
    LA6 Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed LA6 population who provided post-baseline safety data.

    Subject analysis set title
    US1 Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed US1 population who provided post-baseline safety data.

    Subject analysis set title
    LA1 Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed LA1 population who provided post-baseline safety data.

    Subject analysis set title
    LA3 Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed LA3 population who provided post-baseline safety data.

    Subject analysis set title
    US1+US3 Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed US1 and US3 population who provided post-baseline safety data.

    Subject analysis set title
    US2+US4 Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed US2 and US4 population who provided post-baseline safety data.

    Subject analysis set title
    LA3+LA5 Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed LA3 and LA5 population who provided post-baseline safety data.

    Subject analysis set title
    LA4+LA6 Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed LA4 and LA6 population who provided post-baseline safety data.

    Primary: 1. Percentage of Subjects With hSBA Titer >=1:8 - US Subjects

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    End point title
    		 1. Percentage of Subjects With hSBA Titer >=1:8 - US Subjects [1] [2]
    End point description
    End point type
    Primary
    End point timeframe
    13 months of age (one month post-toddler vaccination)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    [2] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US1A (MenACWY-CRM + Infant Vaccines) US2 (Infant Vaccines Only)
    Number of subjects analysed
    86
    74
    Units: Percentages of subjects
    number (confidence interval 95%)
        A (84, 74)
    94 (87 to 98)
    72 (60 to 81)
        C (86, 73)
    98 (92 to 100)
    90 (81 to 96)
        W (85, 73)
    100 (96 to 100)
    58 (45 to 69)
        Y (84, 68)
    100 (96 to 100)
    56 (43 to 68)
    No statistical analyses for this end point

    Primary: 2. Geometric Mean hSBA Titers – US Subjects

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    End point title
    		 2. Geometric Mean hSBA Titers – US Subjects [3]
    End point description
    End point type
    Primary
    End point timeframe
    13 months of age (one month post-toddler vaccination)
    Notes
    [3] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US1A (MenACWY-CRM + Infant Vaccines) US2 (Infant Vaccines Only)
    Number of subjects analysed
    86
    74
    Units: Titers
    geometric mean (confidence interval 95%)
        A Pre-vaccination (84, 74)
    2.51 (2.14 to 2.96)
    2.14 (1.8 to 2.54)
        A Post-vaccination (84, 74)
    77 (55 to 109)
    17 (12 to 25)
        C Pre-vaccination (86, 73)
    7.72 (5.9 to 10)
    2.26 (1.69 to 3.03)
        C Post-vaccination (86, 73)
    227 (155 to 332)
    35 (23 to 54)
        W Pre-vaccination (85, 73)
    14 (11 to 18)
    2.21 (1.69 to 2.9)
        W Post-vaccination (85, 73)
    416 (288 to 602)
    11 (7.59 to 17)
        Y Pre-vaccination (84, 68)
    11 (8.76 to 15)
    2.14 (1.6 to 2.86)
        Y Post-vaccination (84, 68)
    395 (269 to 580)
    10 (6.72 to 16)
    Statistical analysis title
    		 A (Post-vaccination GMT; group ratio US1A:US2)
    Statistical analysis description
    Using the MenACWY GMTs in sero group A, immunogenicity of the fourth dose at 1 month after the 12-month vaccination in those subjects receiving MenACWY at 2, 4, and 6 months was considered superior to the immune response of a single dose given at 12-months of age if the lower limit of the two-sided 95% CI of the ratio of the two GMTs was >= 2.0.
    Comparison groups
    US2 (Infant Vaccines Only) v US1A (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMTs
    Point estimate
    4.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.04
         upper limit
    		 6.74
    Statistical analysis title
    		 C (Post-vaccination GMT; group ratio US1A:US2)
    Statistical analysis description
    Using the MenACWY GMTs in sero group C, immunogenicity of the fourth dose at 1 month after the 12-month vaccination in those subjects receiving MenACWY at 2, 4, and 6 months was considered superior to the immune response of a single dose given at 12-months of age if the lower limit of the two-sided 95% CI of the ratio of the two GMTs was >= 2.0.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US2 (Infant Vaccines Only)
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMTs
    Point estimate
    6.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.16
         upper limit
    		 9.79
    Statistical analysis title
    		 W (Post-vaccination GMT; group ratio US1A:US2)
    Statistical analysis description
    Using the MenACWY GMTs in sero group W, immunogenicity of the fourth dose at 1 month after the 12-month vaccination in those subjects receiving MenACWY at 2, 4, and 6 months was considered superior to the immune response of a single dose given at 12-months of age if the lower limit of the two-sided 95% CI of the ratio of the two GMTs was >= 2.0.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US2 (Infant Vaccines Only)
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMTs
    Point estimate
    37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 24
         upper limit
    		 58
    Statistical analysis title
    		 Y (Post-vaccination GMT; group ratio US1A:US2)
    Statistical analysis description
    Using the MenACWY GMTs in sero group Y, immunogenicity of the fourth dose at 1 month after the 12-month vaccination in those subjects receiving MenACWY at 2, 4, and 6 months was considered superior to the immune response of a single dose given at 12-months of age if the lower limit of the two-sided 95% CI of the ratio of the two GMTs was >= 2.0.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US2 (Infant Vaccines Only)
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMTs
    Point estimate
    38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 24
         upper limit
    		 60

    Secondary: 3. Geometric Mean hSBA Titers Post-infant Series - US Subjects

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    End point title
    		 3. Geometric Mean hSBA Titers Post-infant Series - US Subjects [4]
    End point description
    End point type
    Secondary
    End point timeframe
    7 months of age (one month post infant series)
    Notes
    [4] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US2 (Infant Vaccines Only) US1 Per Protocol Set
    Number of subjects analysed
    90
    212
    Units: Titers
    geometric mean (confidence interval 95%)
        A (Pre-vaccination GMT; N= 65, 177)
    2.1 (1.92 to 2.29)
    2.11 (2 to 2.23)
        A (Post-vaccination GMT; N= 80, 212)
    2.03 (1.53 to 2.7)
    13 (11 to 16)
        C (Pre-vaccination GMT; N= 64, 168)
    2.17 (1.83 to 2.57)
    2.48 (2.23 to 2.75)
        C (Post-vaccination GMT; N= 84, 204)
    2.12 (1.64 to 2.74)
    108 (92 to 127)
        W (Pre-vaccination GMT; N= 66, 165)
    2.71 (2.2 to 3.33)
    3.07 (2.7 to 3.5)
        W (Post-vaccination GMT; N=90, 197)
    2.08 (1.67 to 2.6)
    100 (86 to 116)
        Y (Pre-vaccination GMT; N=62, 150)
    2.13 (1.85 to 2.45)
    2.53 (2.31 to 2.77)
        Y (Post-vaccination GMT; N=84, 182)
    2.03 (1.6 to 2.57)
    73 (62 to 86)
    No statistical analyses for this end point

    Secondary: 4. Percentage of Subjects With hSBA Titer >=1:8 - US Subjects

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    End point title
    		 4. Percentage of Subjects With hSBA Titer >=1:8 - US Subjects [5]
    End point description
    End point type
    Secondary
    End point timeframe
    7 months of age (one month post-infant series)
    Notes
    [5] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US2 (Infant Vaccines Only) US1 Per Protocol Set
    Number of subjects analysed
    90
    212
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A (Pre-vaccination GMT; N= 65, 177)
    3 (0 to 11)
    2 (0 to 5)
        A (Post-vaccination GMT; N= 80, 212)
    1 (0.032 to 7)
    67 (61 to 74)
        C (Pre-vaccination GMT; N= 64, 168)
    5 (1 to 13)
    7 (3 to 11)
        C (Post-vaccination GMT; N= 84, 204)
    1 (0.03 to 6)
    97 (93 to 99)
        W (Pre-vaccination GMT; N= 66, 165)
    11 (4 to 21)
    17 (12 to 24)
        W (Post-vaccination GMT; N=90, 197)
    2 (0 to 8)
    96 (93 to 99)
        Y (Pre-vaccination GMT; N=62, 150 )
    3 (0 to 11)
    5 (2 to 10)
        Y (Post-vaccination GMT; N=84, 182)
    0 (0 to 4)
    96 (92 to 98)
    No statistical analyses for this end point

    Secondary: 5. Percentage of Subjects With hSBA Titer >=1:4 - US Subjects

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    End point title
    		 5. Percentage of Subjects With hSBA Titer >=1:4 - US Subjects [6]
    End point description
    End point type
    Secondary
    End point timeframe
    7 months of age (one month post-infant series)
    Notes
    [6] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US2 (Infant Vaccines Only) US1 Per Protocol Set
    Number of subjects analysed
    90
    212
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A (Pre-vaccination GMT; N= 65, 177)
    3 (0 to 11)
    2 (1 to 6)
        A (Post-vaccination GMT; N= 80, 212)
    1 (0.03 to 7)
    71 (65 to 77)
        C (Pre-vaccination GMT; N= 64, 168)
    5 (1 to 13)
    10 (6 to 16)
        C (Post-vaccination GMT; N= 84, 204)
    2 (0 to 8)
    99 (96 to 100)
        W (Pre-vaccination GMT; N= 66, 165)
    15 (8 to 26)
    22 (16 to 30)
        W (Post-vaccination GMT; N=90, 197)
    2 (0 to 8)
    99 (96 to 100)
        Y (Pre-vaccination GMT; N=62, 150 )
    5 (1 to 13)
    17 (11 to 24)
        Y (Post-vaccination GMT; N=84, 182)
    1 (0.03 to 6)
    98 (95 to 100)
    No statistical analyses for this end point

    Secondary: 6. Geometric Mean hSBA Titers Post-infant Series - LA Subjects

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    End point title
    		 6. Geometric Mean hSBA Titers Post-infant Series - LA Subjects
    End point description
    End point type
    Secondary
    End point timeframe
    7 months of age (one month post-infant series)
    End point values
    		 LA3 Per Protocol Set LA1 Per Protocol Set
    Number of subjects analysed
    272
    277
    Units: Titers
    geometric mean (confidence interval 95%)
        A (Pre-vaccination GMT; N= 271, 272)
    2.03 (1.97 to 2.09)
    2.09 (2.03 to 2.16)
        A (Post-vaccination GMT; N= 268, 277)
    43 (36 to 52)
    31 (26 to 38)
        C (Pre-vaccination GMT; N= 272, 273)
    2.34 (2.19 to 2.49)
    2.32 (2.18 to 2.47)
        C (Post-vaccination GMT; N= 272, 277)
    150 (127 to 177)
    155 (131 to 183)
        W (Pre-vaccination GMT; N= 261, 263)
    2.54 (2.31 to 2.79)
    2.9 (2.64 to 3.18)
        W (Post-vaccination GMT; N=264,271)
    182 (159 to 208)
    259 (227 to 296)
        Y (Pre-vaccination GMT; N=260, 258)
    2.26 (2.14 to 2.39)
    2.35 (2.22 to 2.49)
        Y (Post-vaccination GMT; N=263,272)
    125 (107 to 146)
    159 (136 to 185)
    Statistical analysis title
    		 Serogroup A
    Comparison groups
    LA1 Per Protocol Set v LA3 Per Protocol Set
    Number of subjects included in analysis
    549
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [7]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMTs
    Point estimate
    0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 0.95
    Notes
    [7] - LA1 was noninferior to LA3, if the lower limit of the two-sided 95% CI for the ratio of GMTs between the 2 dose and the 3 dose schedule (GMTLA1/GMTLA3) is > 0.5.
    Statistical analysis title
    		 Serogroup C
    Comparison groups
    LA3 Per Protocol Set v LA1 Per Protocol Set
    Number of subjects included in analysis
    549
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMTs
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 1.31
    Notes
    [8] - LA1 was noninferior to LA3, if the lower limit of the two-sided 95% CI for the ratio of GMTs between the 2 dose and the 3 dose schedule (GMTLA1/GMTLA3) is > 0.5.
    Statistical analysis title
    		 Serogroup W
    Comparison groups
    LA3 Per Protocol Set v LA1 Per Protocol Set
    Number of subjects included in analysis
    549
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [9]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMTs
    Point estimate
    1.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.18
         upper limit
    		 1.72
    Notes
    [9] - LA1 was noninferior to LA3, if the lower limit of the two-sided 95% CI for the ratio of GMTs between the 2 dose and the 3 dose schedule (GMTLA1/GMTLA3) is > 0.5.
    Statistical analysis title
    		 Serogroup Y
    Comparison groups
    LA3 Per Protocol Set v LA1 Per Protocol Set
    Number of subjects included in analysis
    549
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [10]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMTs
    Point estimate
    1.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.02
         upper limit
    		 1.58
    Notes
    [10] - LA1 was noninferior to LA3, if the lower limit of the two-sided 95% CI for the ratio of GMTs between the 2 dose and the 3 dose schedule (GMTLA1/GMTLA3) is > 0.5.

    Secondary: 7. Percentage of Subjects With hSBA Titer >=1:8 - LA Subjects

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    End point title
    		 7. Percentage of Subjects With hSBA Titer >=1:8 - LA Subjects
    End point description
    End point type
    Secondary
    End point timeframe
    7 months of age (one month post-infant series)
    End point values
    		 LA3 Per Protocol Set LA1 Per Protocol Set
    Number of subjects analysed
    272
    277
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A (Pre-vaccination hSBA titer ≥1:8; N= 272, 271)
    0 (0 to 2)
    1 (0 to 4)
        A (Post-vaccination hSBA titer ≥1:8; N= 277, 268)
    89 (85 to 93)
    74 (69 to 79)
        C (Pre-vaccination hSBA titer ≥1:8; N= 273,272)
    4 (2 to 8)
    4 (2 to 7)
        C (Post-vaccination hSBA titer ≥1:8; N= 277, 272)
    97 (94 to 99)
    94 (90 to 96)
        W (Pre-vaccination hSBA titer ≥1:8; N= 263, 261)
    10 (7 to 14)
    16 (12 to 21)
        W (Post-vaccination hSBA titer ≥1:8; N=271,264)
    98 (96 to 100)
    99 (97 to 100)
        Y (Pre-vaccination hSBA titer ≥1:8; N=258, 260)
    3 (2 to 6)
    5 (3 to 9)
        Y (Post-vaccination hSBA titer ≥1:8; N=272,263)
    98 (96 to 99)
    97 (94 to 99)
    Statistical analysis title
    		 Serogroup A
    Comparison groups
    LA1 Per Protocol Set v LA3 Per Protocol Set
    Number of subjects included in analysis
    549
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [11]
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage (hSBA titers >=8) difference
    Point estimate
    -15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.2
         upper limit
    		 -8.5
    Notes
    [11] - LA1 was noninferior to LA3, if the lower limit of the two-sided 95% CI for the difference in percentage of subjects with hSBA ≥ 1:8 and ≥1:4 between the 2 dose and the 3 dose schedule (LA1 - LA3) is greater than -10%.
    Statistical analysis title
    		 Serogroup C
    Comparison groups
    LA1 Per Protocol Set v LA3 Per Protocol Set
    Number of subjects included in analysis
    549
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [12]
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage (hSBA titers >=8) difference
    Point estimate
    -3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7
         upper limit
    		 0.3
    Notes
    [12] - LA1 was noninferior to LA3, if the lower limit of the two-sided 95% CI for the difference in percentage of subjects with hSBA ≥ 1:8 and ≥1:4 between the 2 dose and the 3 dose schedule (LA1 - LA3) is greater than -10%.
    Statistical analysis title
    		 Serogroup W
    Comparison groups
    LA1 Per Protocol Set v LA3 Per Protocol Set
    Number of subjects included in analysis
    549
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [13]
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage (hSBA titers >=8) difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 3.1
    Notes
    [13] - LA1 was noninferior to LA3, if the lower limit of the two-sided 95% CI for the difference in percentage of subjects with hSBA ≥ 1:8 and ≥1:4 between the 2 dose and the 3 dose schedule (LA1 - LA3) is greater than -10%.
    Statistical analysis title
    		 Serogroup Y
    Comparison groups
    LA1 Per Protocol Set v LA3 Per Protocol Set
    Number of subjects included in analysis
    549
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [14]
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage (hSBA titers >=8) difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 1.7
    Notes
    [14] - LA1 was noninferior to LA3, if the lower limit of the two-sided 95% CI for the difference in percentage of subjects with hSBA ≥ 1:8 and ≥1:4 between the 2 dose and the 3 dose schedule (LA1 - LA3) is greater than -10%.

    Secondary: 8. Percentage of Subjects With hSBA Titer >=1:4 - LA Subjects

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    End point title
    		 8. Percentage of Subjects With hSBA Titer >=1:4 - LA Subjects
    End point description
    End point type
    Secondary
    End point timeframe
    7 months of age (one month post-infant series)
    End point values
    		 LA3 Per Protocol Set LA1 Per Protocol Set
    Number of subjects analysed
    272
    277
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A (Pre-vaccination hSBA titer ≥1:4; N= 271, 272)
    1 (0 to 3)
    2 (1 to 5)
        A (Post-vaccination hSBA titer ≥1:4; N= 268, 277)
    91 (87 to 94)
    78 (73 to 83)
        C (Pre-vaccination hSBA titer ≥1:4; N= 272,273)
    10 (7 to 15)
    10 (7 to 14)
        C (Post-vaccination hSBA titer ≥1:4; N= 272, 277)
    98 (96 to 99)
    96 (93 to 98)
        W (Pre-vaccination hSBA titer ≥1:4; N= 261, 263)
    13 (9 to 17)
    17 (13 to 23)
        W (Post-vaccination hSBA titer ≥1:4; N=264,271)
    99 (97 to 100)
    100 (99 to 100)
        Y (Pre-vaccination hSBA titer ≥1:4; N=260, 258)
    8 (5 to 13)
    11 (8 to 16)
        Y (Post-vaccination hSBA titer ≥1:4; N=263,272)
    99 (97 to 100)
    98 (96 to 99)
    No statistical analyses for this end point

    Secondary: 9. Geometric Mean Concentrations or Titers of DTaP, HBV, Hib, Pneumococcal and Polio Antigens at 1 Month After Infant Series Vaccination - US Subjects

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    End point title
    		 9. Geometric Mean Concentrations or Titers of DTaP, HBV, Hib, Pneumococcal and Polio Antigens at 1 Month After Infant Series Vaccination - US Subjects [15]
    End point description
    End point type
    Secondary
    End point timeframe
    7 months of age (one month post-infant series)
    Notes
    [15] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US2 (Infant Vaccines Only) US1 Per Protocol Set
    Number of subjects analysed
    102
    214
    Units: Titers
    geometric mean (confidence interval 95%)
        Diphtheria (N=102, 214)
    2.88 (2.5 to 3.32)
    2.52 (2.28 to 2.78)
        Tetanus (N=102, 214)
    2.31 (2.01 to 2.64)
    2.5 (2.28 to 2.74)
        PT (N=83, 174)
    54 (44 to 66)
    54 (48 to 62)
        FHA (N=83, 174)
    114 (97 to 134)
    118 (106 to 132)
        Pertactin (N=83, 174)
    110 (90 to 134)
    114 (100 to 130)
        Polio Type 1 (N=98, 176)
    441 (361 to 540)
    422 (363 to 491)
        Polio Type 2 (N=98, 175)
    290 (235 to 358)
    348 (297 to 408)
        Polio Type 3 (N=98, 176)
    635 (493 to 818)
    733 (607 to 885)
        Hepatitis B (N=98, 148)
    2112 (1668 to 2674)
    1863 (1538 to 2257)
        Hib (N=101, 213)
    3.56 (2.77 to 4.58)
    4.64 (3.9 to 5.53)
        PnC 4 (N=102, 181)
    2 (1.73 to 2.3)
    1.67 (1.5 to 1.86)
        PnC 6B (N=102, 181)
    2.55 (1.99 to 3.27)
    1.94 (1.61 to 2.34)
        PnC 9V (N=102, 181)
    2.15 (1.83 to 2.53)
    1.83 (1.62 to 2.06)
        PnC 14 (N=102, 181)
    6.79 (5.78 to 7.96)
    6.97 (6.18 to 7.86)
        PnC 18C (N=102, 181)
    2.54 (2.18 to 2.95)
    1.96 (1.75 to 2.19)
        PnC 19F (N=102, 181)
    2.73 (2.39 to 3.13)
    2.24 (2.02 to 2.48)
        PnC 23F (N=102, 181)
    2.15 (1.76 to 2.62)
    1.71 (1.47 to 1.98)
    Statistical analysis title
    		 Diphtheria
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.04
    Statistical analysis title
    		 Tetanus
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 1.28
    Statistical analysis title
    		 PT
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.26
    Statistical analysis title
    		 FHA
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.25
    Statistical analysis title
    		 Pertactin
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.32
    Statistical analysis title
    		 Polio Type 1
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.23
    Statistical analysis title
    		 Polio Type 2
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.93
         upper limit
    		 1.55
    Statistical analysis title
    		 Polio Type 3
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.56
    Statistical analysis title
    		 Hepatitis B
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 1.2
    Statistical analysis title
    		 HIb
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    1.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.97
         upper limit
    		 1.77
    Statistical analysis title
    		 PnC 4
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1
    Statistical analysis title
    		 PnC 6B
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 1.03
    Statistical analysis title
    		 PnC 9V
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.04
    Statistical analysis title
    		 PnC 14
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.26
    Statistical analysis title
    		 PnC 18C
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 0.93
    Statistical analysis title
    		 PnC 19F
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 0.97
    Statistical analysis title
    		 PnC 23F
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the ratio of pertussis GMCs (US1 /US2) must be greater than 0.67; the lower limit of 95% CI for the ratio of all other GMCs (GMCUS1 / GMCUS2) must be greater than 0.50.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 1.02

    Secondary: 10. Seroresponse Rates to DTaP, HBV, Hib, Pneumococcal and Polio Antigens at 1 Month After Infant Series Vaccination - US Subjects

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    End point title
    		 10. Seroresponse Rates to DTaP, HBV, Hib, Pneumococcal and Polio Antigens at 1 Month After Infant Series Vaccination - US Subjects [16]
    End point description
    End point type
    Secondary
    End point timeframe
    7 months of age (one month post-infant series)
    Notes
    [16] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US2 (Infant Vaccines Only) US1 Per Protocol Set
    Number of subjects analysed
    102
    214
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Diphtheria (≥ 0.1 IU/mL) (N=102, 214)
    100 (96 to 100)
    100 (97 to 100)
        Tetanus (≥ 0.1 IU/mL) (N=102, 214)
    100 (96 to 100)
    100 (98 to 100)
        PT(≥ 4-fold rise) (N=83, 174)
    86 (76 to 92)
    87 (81 to 92)
        FHA (≥ 4-fold rise) (N=83, 174)
    80 (69 to 88)
    85 (79 to 90)
        Pertactin (≥ 4-fold rise) (N=83, 174)
    78 (68 to 87)
    76 (69 to 83)
        Polio Type 1 (≥1:8) (N=98, 176)
    100 (96 to 100)
    99 (97 to 100)
        Polio Type 2 (≥1:8) (N=98, 175)
    100 (96 to 100)
    100 (98 to 100)
        Polio Type 3 (≥1:8)(N=98, 176)
    100 (96 to 100)
    99 (97 to 100)
        Hepatitis B (≥10 mIU/mL) (N=98, 148)
    100 (96 to 100)
    99 (96 to 100)
        Hib (≥ 0.15 μg/mL) (N=101, 213)
    100 (96 to 100)
    99 (97 to 100)
        Hib (≥1.0 μg/mL) (N=101, 213)
    84 (76 to 91)
    89 (84 to 93)
        PnC 4 (≥ 0.35 μg/mL) (N=102, 181)
    100 (96 to 100)
    98 (95 to 100)
        PnC 6B (≥ 0.35 μg/mL) (N=102, 181)
    96 (90 to 99)
    88 (83 to 93)
        PnC 9V (≥ 0.35 μg/mL) (N=102, 181)
    98 (93 to 100)
    98 (94 to 99)
        PnC 14 (≥ 0.35 μg/mL) (N=102, 181)
    99 (95 to 100)
    100 (98 to 100)
        PnC 18C (≥ 0.35 μg/mL) (N=102, 181)
    100 (96 to 100)
    97 (94 to 99)
        PnC 19F (≥ 0.35 μg/mL) (N=102, 181)
    100 (96 to 100)
    99 (96 to 100)
        PnC 23F (≥ 0.35 μg/mL) (N=102, 181)
    94 (88 to 98)
    92 (87 to 95)
    Statistical analysis title
    		 Diphtheria
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3
         upper limit
    		 3
    Statistical analysis title
    		 Tetanus
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 4
    Statistical analysis title
    		 PT
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7
         upper limit
    		 12
    Statistical analysis title
    		 FHA
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 17
    Statistical analysis title
    		 Pertactin
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12
         upper limit
    		 10
    Statistical analysis title
    		 Polio Type 1
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3
         upper limit
    		 3
    Statistical analysis title
    		 Polio Type 2
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 4
    Statistical analysis title
    		 Polio Type 3
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3
         upper limit
    		 3
    Statistical analysis title
    		 Hepatitis B
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 3
    Statistical analysis title
    		 Hib (≥ 0.15 μg/mL)
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3
         upper limit
    		 3
    Statistical analysis title
    		 Hib (≥1.0 μg/mL)
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3
         upper limit
    		 14
    Statistical analysis title
    		 PnC 4
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5
         upper limit
    		 2
    Statistical analysis title
    		 PnC 6B
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14
         upper limit
    		 -1
    Statistical analysis title
    		 PnC 9V
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 5
    Statistical analysis title
    		 PnC 14
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 5
    Statistical analysis title
    		 PnC 18C
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6
         upper limit
    		 1
    Statistical analysis title
    		 PnC 19F
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 3
    Statistical analysis title
    		 PnC 23F
    Statistical analysis description
    To assess non-inferiority of US1 over US2, the lower limit of 95% CI for the difference in seroresponse rates (US1 - US2) must be greater than -5% for polio and -10% for all others.
    Comparison groups
    US2 (Infant Vaccines Only) v US1 Per Protocol Set
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8
         upper limit
    		 5

    Secondary: 11. Geometric Mean Concentrations or Titers of DTaP, HBV, Hib, Pneumococcal and Polio Antigens at 1 Month After Infant Series Vaccination - LA Subjects

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    End point title
    		 11. Geometric Mean Concentrations or Titers of DTaP, HBV, Hib, Pneumococcal and Polio Antigens at 1 Month After Infant Series Vaccination - LA Subjects [17]
    End point description
    End point type
    Secondary
    End point timeframe
    7 months of age (one month post-infant series)
    Notes
    [17] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA2 (Infant Vaccines Only) LA4 (Infant Vaccines Only) LA3 Per Protocol Set LA1 Per Protocol Set
    Number of subjects analysed
    123
    137
    283
    287
    Units: Titers
    geometric mean (confidence interval 95%)
        Diphtheria (N=123, 137, 283, 287)
    1.54 (1.32 to 1.81)
    1.77 (1.52 to 2.05)
    1.45 (1.31 to 1.61)
    1.8 (1.62 to 1.99)
        Tetanus (N=123, 137, 283, 287)
    2.19 (1.94 to 2.46)
    2.65 (2.37 to 2.96)
    2.51 (2.33 to 2.71)
    2.41 (2.33 to 2.6)
        PT (N=123, 135, 281, 285)
    45 (39 to 53)
    49 (42 to 56)
    45 (41 to 50)
    47 (43 to 52)
        FHA (N=123, 135, 281, 286)
    97 (85 to 112)
    112 (99 to 128)
    99 (91 to 109)
    102 (93 to 112)
        Pertactin (N=123, 135, 281, 286)
    124 (105 to 146)
    149 (127 to 175)
    119 (106 to 133)
    123 (110 to 137)
        Polio Type 1 (N=112, 120, 252, 265)
    598 (477 to 749)
    684 (550 to 850)
    533 (458 to 619)
    535 (462 to 620)
        Polio Type 2 (N=112, 120, 252, 265)
    366 (289 to 463)
    385 (306 to 483)
    318 (271 to 372)
    353 (302 to 411)
        Polio Type 3 (N=112, 120, 252, 265)
    747 (571 to 977)
    813 (627 to 1054)
    656 (548 to 785)
    710 (596 to 846)
        Hepatitis B (N=104, 118, 237, 243)
    2045 (1682 to 2485)
    1993 (1660 to 2394)
    1900 (1670 to 2162)
    2273 (2001 to 2583)
        Hib (N=123, 137, 283, 287)
    6.01 (4.84 to 7.47)
    6.74 (5.49 to 8.28)
    7.19 (6.23 to 8.29)
    7.64 (6.63 to 8.8)
        PnC 4 (N=116, 126, 256, 268)
    2.24 (1.94 to 2.58)
    2.39 (2.08 to 2.74)
    1.91 (1.74 to 2.1)
    2.07 (1.88 to 2.27)
        PnC 6B (N=116, 124, 255, 264)
    2.21 (1.76 to 2.77)
    2.4 (1.93 to 2.98)
    2.09 (1.8 to 2.44)
    2.15 (1.85 to 2.49)
        PnC 9V (N=116, 126, 256, 268)
    2.21 (1.89 to 2.6)
    2.19 (1.88 to 2.55)
    1.81 (1.63 to 2.02)
    1.89 (1.71 to 2.1)
        PnC 14 (N=116, 126, 256, 268)
    8.06 (6.63 to 9.78)
    9.18 (7.62 to 11)
    7.69 (6.75 to 8.77)
    7.29 (6.42 to 8.29)
        PnC 18C (N=116, 126, 256, 268)
    2.09 (1.78 to 2.44)
    2.26 (1.94 to 2.62)
    1.7 (1.53 to 1.89)
    1.86 (1.68 to 2.07)
        PnC 19F (N=116, 126, 254, 268)
    2.6 (2.2 to 3.06)
    2.53 (2.16 to 2.96)
    2.3 (2.06 to 2.57)
    2.34 (2.1 to 2.6)
        PnC 23F (N=115, 125, 256, 267)
    2.46 (1.99 to 3.03)
    2.42 (1.98 to 2.96)
    2.12 (1.84 to 2.44)
    1.88 (1.64 to 2.16)
    Statistical analysis title
    		 Diphtheria
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [18]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.4
    Notes
    [18] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 Tetanus
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [19]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.27
    Notes
    [19] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 PT
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [20]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.25
    Notes
    [20] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 FHA
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [21]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 1.23
    Notes
    [21] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 Pertactin
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [22]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 1.21
    Notes
    [22] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 Polio Type 1
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [23]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 1.17
    Notes
    [23] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 Polio Type 2
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [24]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.28
    Notes
    [24] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 Polio Type 3
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [25]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.31
    Notes
    [25] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 Hepatitis B
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [26]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.4
    Notes
    [26] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 Hib
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [27]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    1.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.65
    Notes
    [27] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 PnC 4
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [28]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.09
    Notes
    [28] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 PnC 6B
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [29]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.27
    Notes
    [29] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 PnC 9V
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [30]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.04
    Notes
    [30] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 PnC 14
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [31]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.72
         upper limit
    		 1.14
    Notes
    [31] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 PnC 18C
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [32]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.08
    Notes
    [32] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 PnC 19F
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [33]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.1
    Notes
    [33] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 PnC 23F
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [34]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 0.99
    Notes
    [34] - To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the ratio of pertussis GMCs (LA1 / LA2) must be greater than 0.67; the lower limit of the 95% CI for the ratio of all other GMCs (LA1 / LA2) must be greater than 0.50.
    Statistical analysis title
    		 Diphtheria
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [35]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 0.99
    Notes
    [35] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 Tetanus
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [36]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.09
    Notes
    [36] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 PT
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [37]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.1
    Notes
    [37] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 FHA
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [38]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.03
    Notes
    [38] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 Pertactin
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [39]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 0.97
    Notes
    [39] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 Polio Type 1
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [40]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 1.02
    Notes
    [40] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 Polio Type 2
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [41]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.09
    Notes
    [41] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 Polio Type 3
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [42]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 1.11
    Notes
    [42] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 Hepatitis B
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [43]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.19
    Notes
    [43] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 Hib
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [44]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.37
    Notes
    [44] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 PnC 4
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [45]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 0.95
    Notes
    [45] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 PnC 6B
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [46]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.14
    Notes
    [46] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 PnC 9V
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [47]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1
    Notes
    [47] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 PnC 14
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [48]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.05
    Notes
    [48] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 PnC 18C
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [49]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 0.9
    Notes
    [49] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 PnC 19F
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [50]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.1
    Notes
    [50] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.
    Statistical analysis title
    		 PnC 23F
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [51]
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.12
    Notes
    [51] - To assess non-inferiority of LA3 over LA4, the lower limit of two-sided 95% CI for the ratio of pertussis GMCs (LA3 / LA4) must be greater than 0.67; the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3 / LA4) or GMTs (poliovirus antigens) for the other antigens must be greater than 0.50.

    Secondary: 13. Seroresponse Rates to DTaP, HBV, Hib, Pneumococcal and Polio Antigens at 1 Month After Infant Series Vaccination - LA Subjects

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    End point title
    		 13. Seroresponse Rates to DTaP, HBV, Hib, Pneumococcal and Polio Antigens at 1 Month After Infant Series Vaccination - LA Subjects [52]
    End point description
    End point type
    Secondary
    End point timeframe
    7 months of age (one month post-infant series)
    Notes
    [52] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA2 (Infant Vaccines Only) LA4 (Infant Vaccines Only) LA3 Per Protocol Set LA1 Per Protocol Set
    Number of subjects analysed
    123
    137
    283
    287
    Units: Percentage of Subjects
    geometric mean (confidence interval 95%)
        Diphtheria(≥ 0.1 IU/mL) (N=123, 137, 287, 283)
    98 (94 to 100)
    99 (95 to 100)
    99 (96 to 100)
    99 (96 to 100)
        Tetanus (≥ 0.1 IU/mL) (N=123,137,287,283)
    100 (97 to 100)
    100 (97 to 100)
    100 (99 to 100)
    100 (98 to 100)
        PT(≥ 4-fold rise) (N=123,135,285,281)
    86 (79 to 92)
    82 (75 to 88)
    85 (80 to 89)
    85 (81 to 89)
        FHA (≥ 4-fold rise) (N=123,135,286,281)
    86 (79 to 92)
    81 (74 to 88)
    82 (77 to 86)
    84 (79 to 88)
        Pertactin(≥ 4-fold rise)(N=123,135,286,281)
    87 (80 to 92)
    88 (81 to 93)
    86 (82 to 90)
    81 (76 to 85)
        Polio Type 1 (≥1:8) (N=112,120,265,252)
    100 (97 to 100)
    98 (94 to 100)
    99 (97 to 100)
    98 (95 to 99)
        Polio Type 2 (≥1:8) (N=112,120,265,252)
    99 (95 to 100)
    98 (93 to 99)
    98 (95 to 99)
    97 (95 to 99)
        Polio Type 3 (≥1:8) (N=112,120,265,252)
    97 (92 to 99)
    97 (92 to 99)
    96 (93 to 98)
    97 (95 to 99)
        Hepatitis B(≥10 mIU/mL)(N=104,118,243,237)
    100 (97 to 100)
    100 (97 to 100)
    100 (98 to 100)
    100 (98 to 100)
        Hib (≥0.15 μg/mL) (N=123,137,287,283)
    98 (94 to 100)
    99 (96 to 100)
    97 (94 to 99)
    99 (98 to 100)
        Hib (≥1.0 μg/mL) (N=123,137,287,283)
    93 (88 to 97)
    96 (91 to 98)
    93 (90 to 96)
    95 (92 to 97)
        PnC 4 (≥ 0.35 μg/mL) (N=116,126,268,256)
    99 (95 to 100)
    98 (94 to 100)
    97 (94 to 99)
    99 (96 to 100)
        PnC 6B (≥ 0.35 μg/mL) (N=116,124,264,255)
    86 (79 to 92)
    90 (83 to 94)
    91 (87 to 95)
    91 (86 to 94)
        PnC 9V (≥ 0.35 μg/mL) (N=116,126,268,256)
    98 (94 to 100)
    96 (91 to 99)
    97 (94 to 99)
    97 (95 to 99)
        PnC 14 (≥ 0.35 μg/mL) (N=116,126,268,256)
    97 (93 to 99)
    98 (94 to 100)
    98 (95 to 99)
    99 (97 to 100)
        PnC 18C(≥ 0.35 μg/mL) (N=116,126,268,256)
    98 (94 to 100)
    98 (94 to 100)
    95 (91 to 97)
    97 (94 to 98)
        PnC 19F (≥ 0.35 μg/mL)(N=116,126,268,254)
    98 (94 to 100)
    96 (91 to 99)
    98 (96 to 100)
    97 (94 to 98)
        PnC 23F (≥ 0.35 μg/mL)(N=115,125,267,256)
    97 (91 to 99)
    94 (88 to 97)
    95 (91 to 97)
    93 (89 to 96)
    Statistical analysis title
    		 Diphtheria
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.2
         upper limit
    		 4.4
    Statistical analysis title
    		 Tetanus
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 2.6
    Statistical analysis title
    		 PT
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.7
         upper limit
    		 7.1
    Statistical analysis title
    		 FHA
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.2
         upper limit
    		 5.8
    Statistical analysis title
    		 Pertactin
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.9
         upper limit
    		 2.2
    Statistical analysis title
    		 Polio Type 1
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 1
    Statistical analysis title
    		 Polio Type 2
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.6
         upper limit
    		 2.3
    Statistical analysis title
    		 Polio Type 3
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.2
         upper limit
    		 5.1
    Statistical analysis title
    		 Hepatitis B
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 3.5
    Statistical analysis title
    		 Hib(≥ 0.15 μg/mL)
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 5
    Statistical analysis title
    		 Hib (≥1.0 μg/mL)
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.8
         upper limit
    		 7.7
    Statistical analysis title
    		 PnC 4
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3
         upper limit
    		 3.3
    Statistical analysis title
    		 PnC 6B
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.2
         upper limit
    		 12.3
    Statistical analysis title
    		 PnC 9V
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.9
         upper limit
    		 3.6
    Statistical analysis title
    		 PnC 14
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 6.2
    Statistical analysis title
    		 PnC 18C
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 2.9
    Statistical analysis title
    		 PnC 19F
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 2.9
    Statistical analysis title
    		 PnC 23F
    Statistical analysis description
    To assess non-inferiority of LA1 to LA2, the lower limit of the 95% CI for the difference in seroresponse rates (LA1 - LA2) must be greater than -5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA2 (Infant Vaccines Only) v LA1 Per Protocol Set
    Number of subjects included in analysis
    410
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8
         upper limit
    		 1.9
    Statistical analysis title
    		 Diphtheria
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 3.8
    Statistical analysis title
    		 Tetanus
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 2.7
    Statistical analysis title
    		 PT
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 10.7
    Statistical analysis title
    		 FHA
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.1
         upper limit
    		 8.8
    Statistical analysis title
    		 Pertactin
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8
         upper limit
    		 5.7
    Statistical analysis title
    		 Polio Type 1
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 4.7
    Statistical analysis title
    		 Polio Type 2
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3
         upper limit
    		 4.8
    Statistical analysis title
    		 Polio Type 3
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.4
         upper limit
    		 4.5
    Statistical analysis title
    		 Hepatitis B
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 2.7
    Statistical analysis title
    		 Hib (≥ 0.15 μg/mL)
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.3
         upper limit
    		 1
    Statistical analysis title
    		 Hib (≥1.0 μg/mL)
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.6
         upper limit
    		 3
    Statistical analysis title
    		 PnC 4
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.2
         upper limit
    		 3
    Statistical analysis title
    		 PnC 6B
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 9
    Statistical analysis title
    		 PnC 9V
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.8
         upper limit
    		 6
    Statistical analysis title
    		 PnC 14
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.7
         upper limit
    		 3.4
    Statistical analysis title
    		 PnC 18C
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.2
         upper limit
    		 0.8
    Statistical analysis title
    		 PnC 19F
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 7.5
    Statistical analysis title
    		 PnC 23F
    Statistical analysis description
    To assess non-inferiority of LA3 over LA4, the lower limit of the two-sided 95% CI for the difference in seroresponse rates (LA3 - LA4) must be greater than 5% for poliovirus and greater than -10% for all other antigens.
    Comparison groups
    LA4 (Infant Vaccines Only) v LA3 Per Protocol Set
    Number of subjects included in analysis
    420
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.7
         upper limit
    		 7

    Secondary: 14. Percentage of Subjects With hSBA ≥1:4 at 12 Months of Age- US Subjects

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    End point title
    		 14. Percentage of Subjects With hSBA ≥1:4 at 12 Months of Age- US Subjects [53]
    End point description
    End point type
    Secondary
    End point timeframe
    12 Months of Age (before toddler vaccination)
    Notes
    [53] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US2 (Infant Vaccines Only) US1 Per Protocol Set
    Number of subjects analysed
    74
    169
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A (74, 167)
    3 (0 to 9)
    16 (11 to 23)
        C (73, 169)
    8 (3 to 17)
    57 (50 to 65)
        W (73, 166)
    4 (1 to 12)
    81 (74 to 86)
        Y (68, 154)
    1 (0.0037 to 8)
    73 (65 to 80)
    No statistical analyses for this end point

    Secondary: 15. Percentage of Subjects With hSBA ≥1:8 at 12 Months of Age- US Subjects

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    End point title
    		 15. Percentage of Subjects With hSBA ≥1:8 at 12 Months of Age- US Subjects [54]
    End point description
    End point type
    Secondary
    End point timeframe
    12 Months of Age (before toddler vaccination)
    Notes
    [54] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US2 (Infant Vaccines Only) US1 Per Protocol Set
    Number of subjects analysed
    74
    169
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A (74, 167)
    1 (0.034 to 7)
    12 (7 to 18)
        C (73, 169)
    7 (2 to 15)
    52 (44 to 60)
        W (73, 166)
    4 (1 to 12)
    69 (62 to 76)
        Y (68, 154)
    1 (0.0037 to 8)
    60 (52 to 68)
    No statistical analyses for this end point

    Secondary: 16. Geometric Mean Titers – US Subjects

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    End point title
    		 16. Geometric Mean Titers – US Subjects [55]
    End point description
    End point type
    Secondary
    End point timeframe
    12 Months of Age (before toddler vaccination)
    Notes
    [55] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US2 (Infant Vaccines Only) US1 Per Protocol Set
    Number of subjects analysed
    74
    169
    Units: Titers
    geometric mean (confidence interval 95%)
        A (74, 167)
    2.14 (1.8 to 2.54)
    2.78 (2.48 to 3.12)
        C (73, 169)
    2.26 (1.69 to 3.03)
    8.07 (6.66 to 9.77)
        W (73, 166)
    2.21 (1.69 to 2.9)
    14 (12 to 17)
        Y (68, 154)
    2.14 (1.6 to 2.86)
    11 (8.98 to 13)
    No statistical analyses for this end point

    Secondary: 17. Percentage of Subjects With hSBA ≥1:4 at 12 or 16 Months of Age- LA Subjects

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    End point title
    		 17. Percentage of Subjects With hSBA ≥1:4 at 12 or 16 Months of Age- LA Subjects [56]
    End point description
    End point type
    Secondary
    End point timeframe
    12 or 16 Months of Age (before toddler vaccination)
    Notes
    [56] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA2 (Infant Vaccines Only) LA4 (Infant Vaccines Only) LA3 Per Protocol Set LA1 Per Protocol Set
    Number of subjects analysed
    78
    102
    229
    206
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A (N=78, 101, 205, 229)
    1 (0.032 to 7)
    1 (0.025 to 5)
    18 (14 to 24)
    29 (23 to 36)
        C (N=78, 102, 206, 229)
    4 (1 to 11)
    2 (0 to 7)
    32 (26 to 38)
    62 (55 to 68)
        W (N=70, 98, 198, 218)
    4 (1 to 12)
    5 (2 to 12)
    72 (66 to 78)
    95 (92 to 98)
        Y (N=71, 95, 195, 212)
    3 (0 to 10)
    2 (0 to 7)
    65 (58 to 71)
    82 (76 to 87)
    No statistical analyses for this end point

    Secondary: 18. Percentage of Subjects With hSBA ≥1:8 at 12 or 16 Months of Age- LA Subject

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    End point title
    		 18. Percentage of Subjects With hSBA ≥1:8 at 12 or 16 Months of Age- LA Subject [57]
    End point description
    End point type
    Secondary
    End point timeframe
    12 or 16 Months of Age (before-toddler vaccination)
    Notes
    [57] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA2 (Infant Vaccines Only) LA4 (Infant Vaccines Only) LA3 Per Protocol Set LA1 Per Protocol Set
    Number of subjects analysed
    78
    102
    229
    206
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A (N=78, 101, 205, 229)
    0 (0 to 5)
    0 (0 to 4)
    15 (11 to 20)
    25 (20 to 32)
        C (N=78, 102, 206, 229)
    4 (1 to 11)
    1 (0.025 to 5)
    26 (20 to 32)
    57 (50 to 64)
        W (N=70, 98, 198, 218)
    4 (1 to 12)
    5 (2 to 12)
    63 (56 to 69)
    85 (79 to 90)
        Y (N=71, 95, 195, 212)
    3 (0 to 10)
    0 (0 to 4)
    52 (45 to 59)
    72 (65 to 78)
    No statistical analyses for this end point

    Secondary: 19. Geometric Mean Titers - LA Subjects

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    End point title
    		 19. Geometric Mean Titers - LA Subjects [58]
    End point description
    End point type
    Secondary
    End point timeframe
    12 or 16 Months of Age (before pre-toddler vaccination)
    Notes
    [58] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA2 (Infant Vaccines Only) LA4 (Infant Vaccines Only) LA3 Per Protocol Set LA1 Per Protocol Set
    Number of subjects analysed
    78
    102
    229
    206
    Units: Titers
    geometric mean (confidence interval 95%)
        A (N=78, 101, 205, 229)
    2.02 (1.7 to 2.4)
    2.02 (1.74 to 2.35)
    2.96 (2.63 to 3.33)
    4.26 (3.55 to 5.11)
        C (N=78, 102, 206, 229)
    2.18 (1.73 to 2.74)
    2.05 (1.68 to 2.51)
    4.14 (3.54 to 4.84)
    12 (9.33 to 15)
        W (N=70, 98, 198, 218)
    2.34 (1.79 to 3.05)
    2.33 (1.86 to 2.91)
    14 (12 to 18)
    31 (26 to 37)
        Y (N=71, 95, 195, 212)
    2.2 (1.7 to 2.84)
    2.04 (1.64 to 2.55)
    9.45 (7.81 to 11)
    18 (15 to 22)
    No statistical analyses for this end point

    Secondary: 20. Percentage of Subjects (95% CI) With hSBA ≥ 1:4, at 1 Month After Toddler MenACWY Vaccination - US Subjects

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    End point title
    		 20. Percentage of Subjects (95% CI) With hSBA ≥ 1:4, at 1 Month After Toddler MenACWY Vaccination - US Subjects [59]
    End point description
    End point type
    Secondary
    End point timeframe
    13 months of age (one month post-toddler vaccination)
    Notes
    [59] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US1A (MenACWY-CRM + Infant Vaccines) US2 (Infant Vaccines Only)
    Number of subjects analysed
    86
    74
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A Pre-vaccination (84, 74)
    12 (6 to 21)
    3 (0 to 9)
        A Post-vaccination (84, 74)
    94 (87 to 98)
    78 (67 to 87)
        C Pre-vaccination (86, 73)
    53 (42 to 64)
    8 (3 to 17)
        C Post-vaccination (86, 73)
    99 (94 to 100)
    95 (87 to 98)
        W Pre-vaccination (85, 73)
    80 (70 to 88)
    4 (1 to 12)
        W Post-vaccination (85, 73)
    100 (96 to 100)
    73 (61 to 82)
        Y Pre-vaccination (84, 68)
    74 (63 to 83)
    1 (0.037 to 8)
        Y Post-vaccination (84, 68)
    100 (96 to 100)
    62 (49 to 73)
    No statistical analyses for this end point

    Secondary: 21. Percentage of Subjects (95% CI) With hSBA ≥ 1:8 at 1 Month After Toddler MenACWY Vaccination - US Subjects

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    End point title
    		 21. Percentage of Subjects (95% CI) With hSBA ≥ 1:8 at 1 Month After Toddler MenACWY Vaccination - US Subjects [60]
    End point description
    End point type
    Secondary
    End point timeframe
    13 months of age (one month post-toddler vaccination)
    Notes
    [60] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US1A (MenACWY-CRM + Infant Vaccines) US2 (Infant Vaccines Only)
    Number of subjects analysed
    86
    74
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A Pre-vaccination (84, 74)
    10 (4 to 18)
    1 (0.034 to 7)
        A Post-vaccination (84, 74)
    94 (87 to 98)
    72 (60 to 81)
        C Pre-vaccination (86, 73)
    50 (39 to 61)
    7 (2 to 15)
        C Post-vaccination (86, 73)
    98 (92 to 100)
    90 (81 to 96)
        W Pre-vaccination (85, 73)
    71 (60 to 80)
    4 (1 to 12)
        W Post-vaccination (85, 73)
    100 (96 to 100)
    58 (45 to 69)
        Y Pre-vaccination (84, 68)
    61 (49 to 71)
    1 (0.037 to 8)
        Y Post-vaccination (84, 68)
    100 (96 to 100)
    56 (43 to 68)
    No statistical analyses for this end point

    Secondary: 22. Percentage of Subjects (95% CI) With hSBA ≥ 1:16 at 1 Month After Toddler MenACWY Vaccination - US Subjects

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    End point title
    		 22. Percentage of Subjects (95% CI) With hSBA ≥ 1:16 at 1 Month After Toddler MenACWY Vaccination - US Subjects [61]
    End point description
    End point type
    Secondary
    End point timeframe
    13 months of age (one month post-toddler vaccination)
    Notes
    [61] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US1A (MenACWY-CRM + Infant Vaccines) US2 (Infant Vaccines Only)
    Number of subjects analysed
    86
    74
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A Pre-vaccination (84, 74)
    5 (1 to 12)
    1 (0.034 to 7)
        A Post-vaccination (84, 74)
    90 (82 to 96)
    55 (43 to 67)
        C Pre-vaccination (86, 73)
    35 (25 to 46)
    0 (0 to 5)
        C Post-vaccination (86, 73)
    95 (89 to 99)
    78 (67 to 87)
        W Pre-vaccination (85, 73)
    48 (37 to 59)
    3 (0 to 10)
        W Post-vaccination (85, 73)
    100 (96 to 100)
    38 (27 to 50)
        Y Pre-vaccination (84, 68)
    45 (34 to 56)
    1 (0.037 to 8)
        Y Post-vaccination (84, 68)
    100 (96 to 100)
    41 (29 to 54)
    No statistical analyses for this end point

    Secondary: 23. Percentage of Subjects (95% CI) With hSBA ≥1:4 at 1 Month After Toddler MenACWY Vaccination - LA Subjects

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    End point title
    		 23. Percentage of Subjects (95% CI) With hSBA ≥1:4 at 1 Month After Toddler MenACWY Vaccination - LA Subjects [62]
    End point description
    End point type
    Secondary
    End point timeframe
    13 or 17 Months of Age (one month post-toddler vaccination)
    Notes
    [62] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA1A (MenACWY-CRM + Infant Vaccines) LA3A (MenACWY-CRM + Infant Vaccines)
    Number of subjects analysed
    103
    122
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A Pre-vaccination (103, 120)
    28 (20 to 38)
    18 (12 to 26)
        A Post-vaccination (103,120)
    94 (88 to 98)
    95 (89 to 98)
        C Pre-vaccination (102,122)
    61 (51 to 70)
    30 (22 to 38)
        C Post-vaccination (102,122)
    98 (93 to 100)
    98 (94 to 100)
        W Pre-vaccination (98,112)
    97 (91 to 99)
    71 (61 to 79)
        W Post-vaccination (98,112)
    100 (96 to 100)
    100 (97 to 100)
        Y Pre-vaccination (98,109)
    78 (68 to 85)
    61 (52 to 71)
        Y Post-vaccination (98,109)
    99 (94 to 100)
    99 (95 to 100)
    No statistical analyses for this end point

    Secondary: 24. Percentage of Subjects (95% CI) With hSBA ≥1:8 at 1 Month After Toddler MenACWY Vaccination - LA Subjects

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    End point title
    		 24. Percentage of Subjects (95% CI) With hSBA ≥1:8 at 1 Month After Toddler MenACWY Vaccination - LA Subjects [63]
    End point description
    End point type
    Secondary
    End point timeframe
    13 or 17 Months of Age (one month post-toddler vaccination)
    Notes
    [63] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA1A (MenACWY-CRM + Infant Vaccines) LA3A (MenACWY-CRM + Infant Vaccines)
    Number of subjects analysed
    103
    122
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A Pre-vaccination (103, 120)
    23 (16 to 33)
    13 (8 to 21)
        A Post-vaccination (103,120)
    94 (88 to 98)
    95 (89 to 98)
        C Pre-vaccination (102,122)
    57 (47 to 67)
    22 (15 to 31)
        C Post-vaccination (102,122)
    97 (92 to 99)
    98 (94 to 100)
        W Pre-vaccination (98,112)
    84 (75 to 90)
    62 (52 to 71)
        W Post-vaccination (98,112)
    99 (94 to 100)
    100 (97 to 100)
        Y Pre-vaccination (98,109)
    67 (57 to 76)
    47 (37 to 57)
        Y Post-vaccination (98,109)
    99 (94 to 100)
    99 (95 to 100)
    No statistical analyses for this end point

    Secondary: 25. Percentage of Subjects With hSBA ≥ 1:16 at 1 Month After Toddler MenACWY Vaccination - LA Subjects

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    End point title
    		 25. Percentage of Subjects With hSBA ≥ 1:16 at 1 Month After Toddler MenACWY Vaccination - LA Subjects [64]
    End point description
    End point type
    Secondary
    End point timeframe
    13 or 17 Months of Age (one month post-toddler vaccination)
    Notes
    [64] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA1A (MenACWY-CRM + Infant Vaccines) LA3A (MenACWY-CRM + Infant Vaccines)
    Number of subjects analysed
    103
    122
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A Pre-vaccination (103, 120)
    16 (9 to 24)
    9 (5 to 16)
        A Post-vaccination (103,120)
    93 (86 to 97)
    94 (88 to 98)
        C Pre-vaccination (102,122)
    47 (37 to 57)
    18 (12 to 26)
        C Post-vaccination (102,122)
    95 (89 to 98)
    96 (91 to 99)
        W Pre-vaccination (98,112)
    64 (54 to 74)
    50 (40 to 60)
        W Post-vaccination (98,112)
    99 (94 to 100)
    100 (97 to 100)
        Y Pre-vaccination (98,109)
    53 (43 to 63)
    32 (23 to 42)
        Y Post-vaccination (98,109)
    99 (94 to 100)
    98 (94 to 100)
    No statistical analyses for this end point

    Secondary: 26. Geometric Mean hSBA Titers at 1 Month After Toddler MenACWY Vaccination - LA Subjects

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    End point title
    		 26. Geometric Mean hSBA Titers at 1 Month After Toddler MenACWY Vaccination - LA Subjects [65]
    End point description
    End point type
    Secondary
    End point timeframe
    13 or 17 Months of Age (one month post-toddler vaccination)
    Notes
    [65] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA1A (MenACWY-CRM + Infant Vaccines) LA3A (MenACWY-CRM + Infant Vaccines)
    Number of subjects analysed
    103
    122
    Units: Titers
    geometric mean (confidence interval 95%)
        A Pre-vaccination (103, 120)
    3.83 (3.3 to 4.45)
    2.95 (2.57 to 3.39)
        A Post-vaccination (103,120)
    112 (85 to 148)
    146 (113 to 188)
        C Pre-vaccination (102,122)
    11 (8.91 to 13)
    3.83 (3.2 to 4.6)
        C Post-vaccination (102,122)
    279 (218 to 358)
    283 (225 to 355)
        W Pre-vaccination (98,112)
    28 (22 to 34)
    13 (11 to 16)
        W Post-vaccination (98,112)
    762 (604 to 960)
    727 (586 to 903)
        Y Pre-vaccination (98,109)
    16 (13 to 20)
    8.1 (6.58 to 9.96)
        Y Post-vaccination (98,109)
    550 (426 to 710)
    590 (463 to 751)
    No statistical analyses for this end point

    Secondary: 27. Geometric Mean Concentrations of Pneumococcal Antibodies at 1 Month After Toddler Vaccination - US Subjects

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    End point title
    		 27. Geometric Mean Concentrations of Pneumococcal Antibodies at 1 Month After Toddler Vaccination - US Subjects [66]
    End point description
    End point type
    Secondary
    End point timeframe
    13 months of age (one month post-toddler vaccination)
    Notes
    [66] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US1A (MenACWY-CRM + Infant Vaccines) US1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects analysed
    87
    99
    Units: Titers
    geometric mean (confidence interval 95%)
        PnC 4 (N=86, N=99)
    2.9 (2.33 to 3.61)
    3.24 (2.64 to 3.97)
        PnC 6B (N=86, N=99)
    6.82 (5.67 to 8.21)
    8.58 (7.22 to 10)
        PnC 9V (N=86, N=99)
    2.8 (2.26 to 3.47)
    3.13 (2.56 to 3.82)
        PnC 14 (N=86, N=99)
    12 (9.74 to 14)
    15 (12 to 17)
        PnC 18C (N=87, N=98)
    2.76 (2.26 to 3.38)
    2.71 (2.24 to 3.27)
        PnC 19F(N=86, N=99)
    3.63 (3 to 4.39)
    3.48 (2.92 to 4.16)
        PnC 23F (N=87, N=99)
    5.31 (4.2 to 6.71)
    5.63 (4.52 to 7.01)
    Statistical analysis title
    		 PnC 4
    Statistical analysis description
    To assess non-inferiority of US1A over US1B, the lower limit of 95% CI for the ratio of pneumococcal GMCs (US1A / US1B) had to be greater than 0.50.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.2
    Statistical analysis title
    		 PnC 6B
    Statistical analysis description
    To assess non-inferiority of US1A over US1B, the lower limit of 95% CI for the ratio of pneumococcal GMCs (US1A / US1B) had to be greater than 0.50.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 1.02
    Statistical analysis title
    		 PnC 9V
    Statistical analysis description
    To assess non-inferiority of US1A over US1B, the lower limit of 95% CI for the ratio of pneumococcal GMCs (US1A / US1B) had to be greater than 0.50.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.2
    Statistical analysis title
    		 PnC 14
    Statistical analysis description
    To assess non-inferiority of US1A over US1B, the lower limit of 95% CI for the ratio of pneumococcal GMCs (US1A / US1B) had to be greater than 0.50.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.03
    Statistical analysis title
    		 PnC 18C
    Statistical analysis description
    To assess non-inferiority of US1A over US1B, the lower limit of 95% CI for the ratio of pneumococcal GMCs (US1A / US1B) had to be greater than 0.50.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    1.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.34
    Statistical analysis title
    		 PnC 19F
    Statistical analysis description
    To assess non-inferiority of US1A over US1B, the lower limit of 95% CI for the ratio of pneumococcal GMCs (US1A / US1B) had to be greater than 0.50.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 1.34
    Statistical analysis title
    		 PnC 23F
    Statistical analysis description
    To assess non-inferiority of US1A over US1B, the lower limit of 95% CI for the ratio of pneumococcal GMCs (US1A / US1B) had to be greater than 0.50.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.29

    Secondary: 28. Percentage of Subjects With Pneumococcal Antibody GMCs ≥1.0 μg/mL at 1 Month After Toddler Vaccination - US Subjects

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    End point title
    		 28. Percentage of Subjects With Pneumococcal Antibody GMCs ≥1.0 μg/mL at 1 Month After Toddler Vaccination - US Subjects [67]
    End point description
    End point type
    Secondary
    End point timeframe
    13 months of age (one month post-toddler vaccination)
    Notes
    [67] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US1A (MenACWY-CRM + Infant Vaccines) US1B (MenACWY-CRM + Infant Vaccines) US2 (Infant Vaccines Only)
    Number of subjects analysed
    87
    99
    81
    Units: Percentage of Subjects
    number (confidence interval 95%)
        PnC 4 (N=86, N=99, N=81)
    91 (82 to 96)
    90 (82 to 95)
    84 (74 to 91)
        PnC 6B (N=86, N=99, N=80)
    100 (96 to 100)
    96 (90 to 99)
    99 (93 to 100)
        PnC 9V (N=86, N=99, N=80)
    87 (78 to 93)
    91 (83 to 96)
    86 (77 to 93)
        PnC 14 (N=86, N=99, N=81)
    99 (94 to 100)
    100 (96 to 100)
    100 (96 to 100)
        PnC 18C (N=87, N=98, N=81)
    86 (77 to 93)
    92 (85 to 96)
    94 (86 to 98)
        PnC 19F(N=86, N=99, N=80)
    97 (90 to 99)
    93 (86 to 97)
    99 (93 to 100)
        PnC 23F (N=87, N=99, N=80)
    93 (86 to 97)
    95 (89 to 98)
    99 (93 to 100)
    Statistical analysis title
    		 PnC 4
    Statistical analysis description
    To assess non-inferiority of US1A over US1B, the lower limit of 95% CI for the difference in rates (US1A - US1B) had to be greater than -10%.
    Comparison groups
    US1B (MenACWY-CRM + Infant Vaccines) v US1A (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8
         upper limit
    		 10
    Statistical analysis title
    		 PnC 6B
    Statistical analysis description
    To assess non-inferiority of US1A over US1B, the lower limit of 95% CI for the difference in rates (US1A - US1B) had to be greater than -10%.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 10
    Statistical analysis title
    		 PnC 9V
    Statistical analysis description
    To assess non-inferiority of US1A over US1B, the lower limit of 95% CI for the difference in rates (US1A - US1B) had to be greater than -10%.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    -4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13
         upper limit
    		 5
    Statistical analysis title
    		 PnC 14
    Statistical analysis description
    To assess non-inferiority of US1A over US1B, the lower limit of 95% CI for the difference in rates (US1A - US1B) had to be greater than -10%.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6
         upper limit
    		 3
    Statistical analysis title
    		 PnC 18C
    Statistical analysis description
    To assess non-inferiority of US1A over US1B, the lower limit of 95% CI for the difference in rates (US1A - US1B) had to be greater than -10%.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    -6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15
         upper limit
    		 3
    Statistical analysis title
    		 PnC 19F
    Statistical analysis description
    To assess non-inferiority of US1A over US1B, the lower limit of 95% CI for the difference in rates (US1A - US1B) had to be greater than -10%.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 11
    Statistical analysis title
    		 PnC 23F
    Statistical analysis description
    To assess non-inferiority of US1A over US1B, the lower limit of 95% CI for the difference in rates (US1A - US1B) had to be greater than -10%.
    Comparison groups
    US1A (MenACWY-CRM + Infant Vaccines) v US1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 5

    Secondary: 29. Geometric Mean Concentrations of Pneumococcal Antibodies at 1 Month After Toddler Vaccination – LA Subjects

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    End point title
    		 29. Geometric Mean Concentrations of Pneumococcal Antibodies at 1 Month After Toddler Vaccination – LA Subjects [68]
    End point description
    End point type
    Secondary
    End point timeframe
    13 months of age (one month post-toddler vaccination)
    Notes
    [68] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA1A (MenACWY-CRM + Infant Vaccines) LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects analysed
    97
    97
    Units: Concentrations (μg/mL)
    geometric mean (confidence interval 95%)
        PnC 4 (N=97, N=97)
    3.16 (2.63 to 3.8)
    4.02 (3.34 to 4.83)
        PnC 6B (N=96, N=97)
    4.52 (3.42 to 5.97)
    5.61 (4.25 to 7.4)
        PnC 9V (N=97, N=97)
    2.79 (2.34 to 3.31)
    3.77 (3.17 to 4.48)
        PnC 14(N=97, N=97)
    8.91 (7.52 to 11)
    14 (12 to 16)
        PnC 18C (N=97, N=97)
    2.15 (1.79 to 2.58)
    2.77 (2.31 to 3.32)
        PnC 19F (N=97, N=97)
    3.26 (2.62 to 4.05)
    4.26 (3.43 to 5.29)
        PnC 23F (N=97, N=97)
    4.38 (3.51 to 5.48)
    5.92 (4.74 to 7.4)
    Statistical analysis title
    		 PnC 4
    Statistical analysis description
    To assess non-inferiority of LA1A over LA1B, the lower limit of the two-sided 95% CI for the ratio of pneumococcal GMCs (LA1A / LA1B) had to be greater than 0.50.
    Comparison groups
    LA1A (MenACWY-CRM + Infant Vaccines) v LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 1.02
    Statistical analysis title
    		 PnC 6B
    Statistical analysis description
    To assess non-inferiority of LA1A over LA1B, the lower limit of the two-sided 95% CI for the ratio of pneumococcal GMCs (LA1A / LA1B) had to be greater than 0.50.
    Comparison groups
    LA1A (MenACWY-CRM + Infant Vaccines) v LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.2
    Statistical analysis title
    		 PnC 9V
    Statistical analysis description
    To assess non-inferiority of LA1A over LA1B, the lower limit of the two-sided 95% CI for the ratio of pneumococcal GMCs (LA1A / LA1B) had to be greater than 0.50.
    Comparison groups
    LA1A (MenACWY-CRM + Infant Vaccines) v LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 0.94
    Statistical analysis title
    		 PnC 14
    Statistical analysis description
    To assess non-inferiority of LA1A over LA1B, the lower limit of the two-sided 95% CI for the ratio of pneumococcal GMCs (LA1A / LA1B) had to be greater than 0.50.
    Comparison groups
    LA1A (MenACWY-CRM + Infant Vaccines) v LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 0.82
    Statistical analysis title
    		 PnC 18C
    Statistical analysis description
    To assess non-inferiority of LA1A over LA1B, the lower limit of the two-sided 95% CI for the ratio of pneumococcal GMCs (LA1A / LA1B) had to be greater than 0.50.
    Comparison groups
    LA1A (MenACWY-CRM + Infant Vaccines) v LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 1.01
    Statistical analysis title
    		 PnC 19F
    Statistical analysis description
    To assess non-inferiority of LA1A over LA1B, the lower limit of the two-sided 95% CI for the ratio of pneumococcal GMCs (LA1A / LA1B) had to be greater than 0.50.
    Comparison groups
    LA1A (MenACWY-CRM + Infant Vaccines) v LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 1.04
    Statistical analysis title
    		 PnC 23F
    Statistical analysis description
    To assess non-inferiority of LA1A over LA1B, the lower limit of the two-sided 95% CI for the ratio of pneumococcal GMCs (LA1A / LA1B) had to be greater than 0.50.
    Comparison groups
    LA1A (MenACWY-CRM + Infant Vaccines) v LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.01

    Secondary: 30. Percentage of Subjects With Pneumococcal Antibody Concentration ≥1.0 μg/mL at 1 Month After Toddler Vaccination - LA Subjects

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    End point title
    		 30. Percentage of Subjects With Pneumococcal Antibody Concentration ≥1.0 μg/mL at 1 Month After Toddler Vaccination - LA Subjects [69]
    End point description
    End point type
    Secondary
    End point timeframe
    13 months of age (one month post-toddler vaccination)
    Notes
    [69] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA1A (MenACWY-CRM + Infant Vaccines) LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects analysed
    97
    97
    Units: Percentage of Subjects
    number (confidence interval 95%)
        PnC 4 (N=97, N=97)
    93 (86 to 97)
    95 (88 to 98)
        PnC 6B (N=96, N=97)
    86 (78 to 93)
    89 (81 to 94)
        PnC 9V (N=97, N=97)
    92 (84 to 96)
    95 (88 to 98)
        PnC 14(N=97, N=97)
    99 (94 to 100)
    100 (96 to 100)
        PnC 18C (N=97, N=97)
    80 (71 to 88)
    95 (88 to 98)
        PnC 19F (N=97, N=97)
    90 (82 to 95)
    93 (86 to 97)
        PnC 23F (N=97, N=97)
    95 (88 to 98)
    95 (88 to 98)
    Statistical analysis title
    		 PnC 4
    Statistical analysis description
    To assess non-inferiority of LA1A over LA1B, the lower limit of the two-sided 95% CI for the difference in rates (LA1A - LA1B) had to be greater than -10%.
    Comparison groups
    LA1A (MenACWY-CRM + Infant Vaccines) v LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.6
         upper limit
    		 5.2
    Statistical analysis title
    		 PnC 6B
    Statistical analysis description
    To assess non-inferiority of LA1A over LA1B, the lower limit of the two-sided 95% CI for the difference in rates (LA1A - LA1B) had to be greater than -10%.
    Comparison groups
    LA1A (MenACWY-CRM + Infant Vaccines) v LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.9
         upper limit
    		 7.3
    Statistical analysis title
    		 PnC 9V
    Statistical analysis description
    To assess non-inferiority of LA1A over LA1B, the lower limit of the two-sided 95% CI for the difference in rates (LA1A - LA1B) had to be greater than -10%.
    Comparison groups
    LA1A (MenACWY-CRM + Infant Vaccines) v LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.9
         upper limit
    		 4.3
    Statistical analysis title
    		 PnC 14
    Statistical analysis description
    To assess non-inferiority of LA1A over LA1B, the lower limit of the two-sided 95% CI for the difference in rates (LA1A - LA1B) had to be greater than -10%.
    Comparison groups
    LA1A (MenACWY-CRM + Infant Vaccines) v LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.6
         upper limit
    		 2.7
    Statistical analysis title
    		 PnC 18C
    Statistical analysis description
    To assess non-inferiority of LA1A over LA1B, the lower limit of the two-sided 95% CI for the difference in rates (LA1A - LA1B) had to be greater than -10%.
    Comparison groups
    LA1A (MenACWY-CRM + Infant Vaccines) v LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.1
         upper limit
    		 -5.6
    Statistical analysis title
    		 PnC 19F
    Statistical analysis description
    To assess non-inferiority of LA1A over LA1B, the lower limit of the two-sided 95% CI for the difference in rates (LA1A - LA1B) had to be greater than -10%.
    Comparison groups
    LA1A (MenACWY-CRM + Infant Vaccines) v LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.6
         upper limit
    		 5.2
    Statistical analysis title
    		 PnC 23F
    Statistical analysis description
    To assess non-inferiority of LA1A over LA1B, the lower limit of the two-sided 95% CI for the difference in rates (LA1A - LA1B) had to be greater than -10%.
    Comparison groups
    LA1A (MenACWY-CRM + Infant Vaccines) v LA1B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7
         upper limit
    		 7

    Secondary: 31. Geometric Mean Concentrations or Titers of DTaP and Hib Antigens at 1 Month After Toddler Vaccination - LA Subjects

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    End point title
    		 31. Geometric Mean Concentrations or Titers of DTaP and Hib Antigens at 1 Month After Toddler Vaccination - LA Subjects [70]
    End point description
    End point type
    Secondary
    End point timeframe
    17 months of age (one month post-toddler vaccination)
    Notes
    [70] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA3A (MenACWY-CRM + Infant Vaccines) LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects analysed
    118
    101
    Units: Titers
    geometric mean (confidence interval 95%)
        Diphtheria (N=118, N=101)
    5.4 (4.74 to 6.15)
    5.16 (4.48 to 5.94)
        Tetanus (N=118, N=101)
    6.17 (5.29 to 7.2)
    6.58 (5.57 to 7.77)
        PT (N=113, N=99)
    68 (58 to 80)
    62 (52 to 73)
        FHA (N=113, N=99)
    245 (208 to 288)
    215 (181 to 256)
        Pertactin (N=113, N=99)
    238 (198 to 286)
    197 (161 to 240)
        Hib (N=117, N=101)
    35 (28 to 43)
    41 (32 to 51)
    Statistical analysis title
    		 Diphtheria
    Statistical analysis description
    To assess non-inferiority of LA3A over LA3B, the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3A/LA3B) had to be greater than 0.67 for PT, FHA and pertactin and greater than 0.50 for Hib, diphtheria and tetanus.
    Comparison groups
    LA3A (MenACWY-CRM + Infant Vaccines) v LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.27
    Statistical analysis title
    		 Tetanus
    Statistical analysis description
    To assess non-inferiority of LA3A over LA3B, the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3A/LA3B) had to be greater than 0.67 for PT, FHA and pertactin and greater than 0.50 for Hib, diphtheria and tetanus.
    Comparison groups
    LA3A (MenACWY-CRM + Infant Vaccines) v LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.18
    Statistical analysis title
    		 PT
    Statistical analysis description
    To assess non-inferiority of LA3A over LA3B, the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3A/LA3B) had to be greater than 0.67 for PT, FHA and pertactin and greater than 0.50 for Hib, diphtheria and tetanus.
    Comparison groups
    LA3A (MenACWY-CRM + Infant Vaccines) v LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.4
    Statistical analysis title
    		 FHA
    Statistical analysis description
    To assess non-inferiority of LA3A over LA3B, the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3A/LA3B) had to be greater than 0.67 for PT, FHA and pertactin and greater than 0.50 for Hib, diphtheria and tetanus.
    Comparison groups
    LA3A (MenACWY-CRM + Infant Vaccines) v LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.44
    Statistical analysis title
    		 Pertactin
    Statistical analysis description
    To assess non-inferiority of LA3A over LA3B, the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3A/LA3B) had to be greater than 0.67 for PT, FHA and pertactin and greater than 0.50 for Hib, diphtheria and tetanus.
    Comparison groups
    LA3A (MenACWY-CRM + Infant Vaccines) v LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    1.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 1.59
    Statistical analysis title
    		 Hib
    Statistical analysis description
    To assess non-inferiority of LA3A over LA3B, the lower limit of the two-sided 95% CI for the ratio of GMCs (LA3A/LA3B) had to be greater than 0.67 for PT, FHA and pertactin and greater than 0.50 for Hib, diphtheria and tetanus.
    Comparison groups
    LA3A (MenACWY-CRM + Infant Vaccines) v LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANOVA
    Parameter type
    		 Ratio of GMCs
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.16

    Secondary: 32. Seroresponse Rates to DTaP and Hib Antigens at 1 Month After Toddler Vaccination - LA Subjects

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    End point title
    		 32. Seroresponse Rates to DTaP and Hib Antigens at 1 Month After Toddler Vaccination - LA Subjects [71]
    End point description
    End point type
    Secondary
    End point timeframe
    17 months of age (one month post-toddler vaccination)
    Notes
    [71] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA3A (MenACWY-CRM + Infant Vaccines) LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects analysed
    118
    101
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Diphtheria (≥1.0 IU/mL) (N=118, N=101)
    98 (94 to 100)
    98 (93 to 100)
        Tetanus (≥1.0 IU/mL) (N=118, N=101)
    98 (94 to 100)
    98 (93 to 100)
        PT (≥4 fold rise) (N=113, N=99)
    89 (82 to 94)
    84 (75 to 90)
        FHA (≥4-fold rise) (N=113, N=99)
    87 (79 to 92)
    88 (80 to 94)
        Pertactin (≥4-fold rise) (N=113, N=99)
    89 (82 to 94)
    88 (80 to 94)
        Hib (≥0.15 μg/mL) (N=117, N=101)
    100 (97 to 100)
    100 (96 to 100)
        Hib (≥1.0 μg/mL) (N=117, N=101)
    100 (97 to 100)
    99 (95 to 100)
    Statistical analysis title
    		 Diphtheria
    Statistical analysis description
    To assess non-inferiority of LA3A over LA3B, The lower limit of the two-sided 95% CI for the difference (LA3A-LA3B) in percentages of subjects with seroresponse against diphtheria, tetanus, Hib and pertussis antigens (except FHA for ≥4 fold rise) was greater than -10%
    Comparison groups
    LA3A (MenACWY-CRM + Infant Vaccines) v LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.2
         upper limit
    		 5.4
    Statistical analysis title
    		 Tetanus
    Statistical analysis description
    To assess non-inferiority of LA3A over LA3B, The lower limit of the two-sided 95% CI for the difference (LA3A-LA3B) in percentages of subjects with seroresponse against diphtheria, tetanus, Hib and pertussis antigens (except FHA for ≥4 fold rise) was greater than -10%
    Comparison groups
    LA3A (MenACWY-CRM + Infant Vaccines) v LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.2
         upper limit
    		 5.4
    Statistical analysis title
    		 PT
    Statistical analysis description
    To assess non-inferiority of LA3A over LA3B, The lower limit of the two-sided 95% CI for the difference (LA3A-LA3B) in percentages of subjects with seroresponse against diphtheria, tetanus, Hib and pertussis antigens (except FHA for ≥4 fold rise) was greater than -10%
    Comparison groups
    LA3A (MenACWY-CRM + Infant Vaccines) v LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.6
         upper limit
    		 15.2
    Statistical analysis title
    		 FHA
    Statistical analysis description
    To assess non-inferiority of LA3A over LA3B, The lower limit of the two-sided 95% CI for the difference (LA3A-LA3B) in percentages of subjects with seroresponse against diphtheria, tetanus, Hib and pertussis antigens (except FHA for ≥4 fold rise) was greater than -10%
    Comparison groups
    LA3A (MenACWY-CRM + Infant Vaccines) v LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.2
         upper limit
    		 8.2
    Statistical analysis title
    		 Pertactin
    Statistical analysis description
    To assess non-inferiority of LA3A over LA3B, The lower limit of the two-sided 95% CI for the difference (LA3A-LA3B) in percentages of subjects with seroresponse against diphtheria, tetanus, Hib and pertussis antigens (except FHA for ≥4 fold rise) was greater than -10%
    Comparison groups
    LA3A (MenACWY-CRM + Infant Vaccines) v LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.2
         upper limit
    		 10.6
    Statistical analysis title
    		 Hib (≥ 0.15 μg/mL)
    Statistical analysis description
    To assess non-inferiority of LA3A over LA3B, The lower limit of the two-sided 95% CI for the difference (LA3A-LA3B) in percentages of subjects with seroresponse against diphtheria, tetanus, Hib and pertussis antigens (except FHA for ≥4 fold rise) was greater than -10%
    Comparison groups
    LA3A (MenACWY-CRM + Infant Vaccines) v LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.1
         upper limit
    		 3.6
    Statistical analysis title
    		 Hib (≥1.0 μg/mL)
    Statistical analysis description
    To assess non-inferiority of LA3A over LA3B, The lower limit of the two-sided 95% CI for the difference (LA3A-LA3B) in percentages of subjects with seroresponse against diphtheria, tetanus, Hib and pertussis antigens (except FHA for ≥4 fold rise) was greater than -10%
    Comparison groups
    LA3A (MenACWY-CRM + Infant Vaccines) v LA3B (MenACWY-CRM + Infant Vaccines)
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Miettinen and Nurminen CI
    Parameter type
    		 Percentage Difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.2
         upper limit
    		 5.3

    Secondary: 33. Percentage of Subjects With hSBA ≥1:8 at 1 Month After 1st (LA2) or 2nd (LA4) Toddler MenACWY Vaccination - LA Subjects

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    End point title
    		 33. Percentage of Subjects With hSBA ≥1:8 at 1 Month After 1st (LA2) or 2nd (LA4) Toddler MenACWY Vaccination - LA Subjects [72]
    End point description
    End point type
    Secondary
    End point timeframe
    13 or 16 months of age (one month post 1st or 2nd toddler vaccination)
    Notes
    [72] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA2 (Infant Vaccines Only) LA4 (Infant Vaccines Only)
    Number of subjects analysed
    78
    102
    Units: Percentage of Subjects
    number (confidence interval 95%)
        A Pre-vaccination (78, 101)
    0 (0 to 5)
    0 (0 to 4)
        A Post-vaccination ((78, 101)
    74 (63 to 84)
    97 (92 to 99)
        C Pre-vaccination (78, 102)
    4 (1 to 11)
    1 (0.025 to 5)
        C Post-vaccination (78, 102)
    91 (82 to 96)
    100 (96 to 100)
        W Pre-vaccination (70, 98)
    4 (1 to 12)
    5 (2 to 12)
        W Post-vaccination (70, 98)
    79 (67 to 87)
    100 (96 to 100)
        Y Pre-vaccination (71, 95)
    3 (0 to 10)
    0 (0 to 4)
        Y Post-vaccination (71, 95)
    72 (60 to 82)
    100 (96 to 100)
    No statistical analyses for this end point

    Secondary: 34. Geometric Mean hSBA Titers at 1 Month After 1st (LA2) or 2nd (LA4) Toddler MenACWY Vaccination - LA Subjects

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    End point title
    		 34. Geometric Mean hSBA Titers at 1 Month After 1st (LA2) or 2nd (LA4) Toddler MenACWY Vaccination - LA Subjects [73]
    End point description
    End point type
    Secondary
    End point timeframe
    13 or 16 months of age (one month post 1st or 2nd toddler vaccination)
    Notes
    [73] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 LA2 (Infant Vaccines Only) LA4 (Infant Vaccines Only)
    Number of subjects analysed
    78
    102
    Units: Titers
    geometric mean (confidence interval 95%)
        A Pre-vaccination (78, 101)
    2.02 (1.7 to 2.4)
    2.02 (1.74 to 2.35)
        A Post-vaccination (78, 101)
    25 (18 to 34)
    128 (97 to 169)
        C Pre-vaccination (78, 102)
    2.18 (1.73 to 2.74)
    2.05 (1.68 to 2.51)
        C Post-vaccination (78, 102)
    45 (34 to 60)
    501 (391 to 643)
        W Pre-vaccination (70, 98)
    2.34 (1.79 to 3.05)
    2.33 (1.86 to 2.91)
        W Post-vaccination (70, 98)
    22 (16 to 28)
    394 (313 to 497)
        Y Pre-vaccination (71, 95)
    2.2 (1.7 to 2.84)
    2.04 (1.64 to 2.55)
        Y Post-vaccination (71, 95)
    15 (11 to 20)
    329 (254 to 426)
    No statistical analyses for this end point

    Secondary: 35. Number of Subjects With Solicited Local and Systemic Reactions Post First Vaccination – Infant Series

    		 Close Top of page
    End point title
    		 35. Number of Subjects With Solicited Local and Systemic Reactions Post First Vaccination – Infant Series [74]
    End point description
    End point type
    Secondary
    End point timeframe
    7 days after vaccination
    Notes
    [74] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US1A (MenACWY-CRM + Infant Vaccines) US1B (MenACWY-CRM + Infant Vaccines) US2 (Infant Vaccines Only) US3 (MenACWY-CRM + Infant Vaccines) LA2 (Infant Vaccines Only) LA4 (Infant Vaccines Only) LA5 (MenACWY-CRM + Infant Vaccines) US4 Safety Set LA6 Safety Set US1 Safety Set LA1 Safety Set LA3 Safety Set
    Number of subjects analysed
    153
    165
    159
    677
    148
    150
    1424
    345
    709
    318
    301
    301
    Units: Subjects
    number (not applicable)
        Erythema (mm) - Any
    10
    17
    23
    66
    62
    65
    542
    54
    273
    27
    86
    86
        Erythema (mm) - Severe
    0
    0
    2
    0
    0
    1
    1
    4
    4
    0
    0
    1
        Induration (mm) - Any
    10
    14
    25
    61
    56
    53
    249
    44
    126
    24
    74
    72
        Induration (mm) - Severe
    0
    0
    0
    0
    0
    0
    2
    1
    0
    0
    1
    0
        Tenderness - Any
    64
    76
    69
    324
    96
    95
    916
    161
    501
    140
    154
    170
        Tenderness - Severe
    3
    4
    6
    25
    19
    20
    92
    19
    74
    7
    30
    22
        Body Temp. ( >= 38° C )
    13
    6
    7
    32
    12
    5
    211
    21
    97
    19
    15
    18
        Change in Eating Habits - Any
    42
    46
    34
    171
    30
    16
    250
    96
    127
    88
    37
    44
        Change in Eating Habits - Severe
    1
    1
    1
    8
    0
    1
    6
    2
    4
    2
    2
    0
        Diarrhea - Any
    24
    23
    17
    107
    20
    22
    222
    46
    96
    47
    42
    44
        Diarrhea - Severe
    2
    0
    1
    3
    0
    0
    2
    1
    2
    2
    1
    1
        Irritability - Any
    82
    107
    96
    419
    62
    59
    508
    211
    240
    189
    121
    99
        Irritability - Severe
    6
    2
    4
    24
    2
    2
    22
    12
    2
    8
    7
    4
        Persistent Crying - Any
    43
    74
    49
    252
    53
    43
    479
    125
    258
    117
    95
    87
        Persistent Crying - Severe
    1
    2
    5
    11
    3
    8
    29
    8
    21
    3
    5
    11
        Rash - Any
    6
    9
    5
    16
    6
    4
    98
    11
    55
    15
    11
    12
        Rash - Severe
    3
    4
    3
    4
    2
    1
    54
    3
    26
    7
    7
    4
        Sleepiness - Any
    83
    104
    76
    354
    53
    52
    727
    173
    381
    187
    106
    93
        Sleepiness - Severe
    2
    3
    0
    14
    2
    4
    21
    3
    14
    5
    8
    6
        Vomiting - Any
    15
    18
    14
    67
    9
    17
    215
    36
    100
    33
    25
    29
        Vomiting - Severe
    0
    0
    0
    0
    0
    1
    2
    1
    1
    0
    0
    1
        Analgesic / Antipyretic medication used
    105
    120
    110
    447
    75
    80
    996
    223
    510
    225
    155
    159
    No statistical analyses for this end point

    Secondary: 36. Number of Subjects With Solicited Local and Systemic Reactions Post Second Vaccination – Infant Series

    		 Close Top of page
    End point title
    		 36. Number of Subjects With Solicited Local and Systemic Reactions Post Second Vaccination – Infant Series [75]
    End point description
    End point type
    Secondary
    End point timeframe
    7 days after vaccination
    Notes
    [75] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US1A (MenACWY-CRM + Infant Vaccines) US1B (MenACWY-CRM + Infant Vaccines) US2 (Infant Vaccines Only) US3 (MenACWY-CRM + Infant Vaccines) LA4 (Infant Vaccines Only) LA5 (MenACWY-CRM + Infant Vaccines) US4 Safety Set LA6 Safety Set US1 Safety Set LA3 Safety Set
    Number of subjects analysed
    141
    150
    151
    645
    150
    1424
    325
    709
    291
    301
    Units: Subjects
    number (not applicable)
        Erythema (mm) - Any
    14
    19
    35
    75
    45
    583
    60
    311
    33
    92
        Erythema (mm) - Severe
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
        Induration (mm) - Any
    16
    16
    27
    45
    36
    194
    48
    126
    32
    73
        Induration (mm) - Severe
    1
    0
    0
    0
    0
    0
    3
    0
    1
    0
        Tenderness - Any
    59
    59
    56
    230
    59
    726
    137
    401
    118
    115
        Tenderness - Severe
    1
    0
    2
    13
    5
    49
    11
    45
    1
    13
        Body Temp. ( >= 38° C )
    17
    6
    15
    49
    13
    223
    28
    122
    23
    23
        Change in Eating Habits - Any
    25
    21
    20
    122
    12
    160
    64
    90
    46
    28
        Change in Eating Habits - Severe
    0
    0
    0
    3
    0
    6
    0
    5
    0
    3
        Diarrhea - Any
    16
    10
    11
    53
    14
    149
    35
    90
    26
    28
        Diarrhea - Severe
    0
    1
    1
    1
    0
    4
    2
    1
    1
    1
        Irritability - Any
    83
    80
    83
    342
    41
    414
    182
    209
    163
    82
        Irritability - Severe
    2
    0
    3
    14
    0
    13
    9
    5
    2
    3
        Persistent Crying - Any
    42
    41
    34
    178
    22
    294
    107
    187
    83
    42
        Persistent Crying - Severe
    0
    0
    0
    5
    1
    14
    4
    10
    0
    4
        Rash - Any
    3
    5
    4
    24
    2
    97
    13
    46
    8
    13
        Rash - Severe
    3
    1
    1
    6
    1
    52
    4
    29
    4
    5
        Sleepiness - Any
    69
    56
    47
    238
    26
    485
    131
    237
    125
    62
        Sleepiness - Severe
    0
    0
    1
    3
    1
    13
    2
    7
    0
    4
        Vomiting - Any
    8
    9
    7
    49
    10
    136
    27
    75
    17
    20
        Vomiting - Severe
    0
    0
    0
    0
    0
    3
    1
    0
    0
    1
        Analgesic / Antipyretic medication used
    94
    91
    96
    385
    61
    857
    201
    430
    185
    131
    No statistical analyses for this end point

    Secondary: 37. Number of Subjects With Solicited Local and Systemic Reactions Post Third Vaccination – Infant Series

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    End point title
    		 37. Number of Subjects With Solicited Local and Systemic Reactions Post Third Vaccination – Infant Series [76]
    End point description
    End point type
    Secondary
    End point timeframe
    7 days after vaccination
    Notes
    [76] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US1A (MenACWY-CRM + Infant Vaccines) US1B (MenACWY-CRM + Infant Vaccines) US2 (Infant Vaccines Only) US3 (MenACWY-CRM + Infant Vaccines) LA2 (Infant Vaccines Only) LA4 (Infant Vaccines Only) LA5 (MenACWY-CRM + Infant Vaccines) US4 Safety Set LA6 Safety Set US1 Safety Set LA1 Safety Set LA3 Safety Set
    Number of subjects analysed
    138
    145
    143
    627
    131
    147
    1357
    311
    679
    283
    297
    290
    Units: Subjects
    number (not applicable)
        Erythema (mm) - Any
    16
    18
    28
    92
    27
    38
    485
    67
    273
    34
    69
    64
        Erythema (mm) - Severe
    0
    0
    1
    0
    0
    0
    1
    1
    1
    0
    0
    1
        Induration (mm) - Any
    15
    15
    29
    59
    25
    32
    125
    53
    73
    30
    54
    64
        Induration (mm) - Severe
    0
    0
    2
    0
    0
    0
    0
    1
    0
    0
    0
    1
        Tenderness - Any
    37
    45
    45
    189
    40
    50
    504
    92
    306
    82
    92
    78
        Tenderness - Severe
    0
    0
    1
    1
    2
    1
    21
    7
    14
    0
    6
    2
        Body Temp. ( >= 38° C )
    4
    9
    14
    33
    10
    14
    164
    20
    101
    13
    13
    26
        Change in Eating Habits - Any
    19
    22
    18
    94
    11
    9
    126
    39
    66
    41
    25
    23
        Change in Eating Habits - Severe
    0
    0
    1
    3
    1
    0
    5
    2
    3
    0
    1
    1
        Diarrhea - Any
    13
    9
    9
    41
    8
    11
    97
    26
    58
    22
    17
    12
        Diarrhea - Severe
    0
    0
    0
    2
    1
    0
    2
    1
    3
    0
    1
    0
        Irritability - Any
    58
    73
    70
    285
    29
    28
    311
    157
    164
    131
    57
    62
        Irritability - Severe
    1
    1
    0
    4
    1
    0
    5
    6
    2
    2
    0
    2
        Persistent Crying - Any
    28
    26
    24
    135
    15
    12
    181
    74
    118
    54
    28
    27
        Persistent Crying - Severe
    0
    0
    0
    4
    2
    0
    11
    4
    2
    0
    2
    0
        Rash - Any
    2
    9
    4
    14
    1
    1
    62
    8
    29
    11
    8
    6
        Rash - Severe
    1
    4
    3
    2
    0
    1
    29
    1
    10
    5
    5
    3
        Sleepiness - Any
    37
    41
    39
    179
    15
    17
    317
    91
    164
    78
    38
    45
        Sleepiness - Severe
    0
    0
    0
    6
    0
    0
    6
    1
    3
    0
    1
    1
        Vomiting - Any
    6
    6
    9
    31
    9
    12
    104
    20
    52
    12
    16
    11
        Vomiting - Severe
    0
    0
    0
    0
    1
    0
    1
    1
    1
    0
    2
    1
        Analgesic / Antipyretic medication used
    75
    82
    96
    349
    38
    51
    592
    178
    342
    157
    93
    90
    No statistical analyses for this end point

    Secondary: 38. Number of Subjects With Solicited Local and Systemic Reactions After Vaccination at 12 Months of Age

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    End point title
    		 38. Number of Subjects With Solicited Local and Systemic Reactions After Vaccination at 12 Months of Age [77]
    End point description
    End point type
    Secondary
    End point timeframe
    7 days after vaccination
    Notes
    [77] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US1A (MenACWY-CRM + Infant Vaccines) US1B (MenACWY-CRM + Infant Vaccines) US3 (MenACWY-CRM + Infant Vaccines) LA1A (MenACWY-CRM + Infant Vaccines) LA1B (MenACWY-CRM + Infant Vaccines) LA5 (MenACWY-CRM + Infant Vaccines) US4B+US4C Safety Set US1A + US3 Safety Set US2+US4A Safety Set LA2+LA4+LA6A Safety Set LA6B+LA6C Safety Set
    Number of subjects analysed
    122
    124
    582
    145
    143
    1275
    261
    704
    137
    564
    349
    Units: Subjects
    number (not applicable)
        Erythema (mm) - Any
    11
    16
    70
    36
    33
    309
    49
    81
    18
    166
    67
        Erythema (mm) - Severe
    0
    0
    2
    0
    1
    0
    1
    2
    1
    2
    0
        Induration (mm) - Any
    10
    13
    34
    32
    28
    84
    39
    44
    12
    72
    43
        Induration (mm) - Severe
    0
    0
    0
    0
    1
    0
    1
    0
    0
    1
    0
        Tenderness - Any
    28
    31
    149
    35
    32
    392
    75
    177
    38
    184
    100
        Tenderness - Severe
    0
    0
    2
    6
    2
    8
    1
    2
    0
    2
    3
        Body Temp. ( >= 38° C )
    14
    10
    35
    16
    12
    188
    20
    49
    12
    84
    40
        Change in Eating Habits - Any
    21
    17
    80
    10
    11
    138
    29
    101
    20
    56
    46
        Change in Eating Habits - Severe
    1
    2
    6
    1
    0
    5
    1
    7
    1
    4
    0
        Diarrhea - Any
    5
    14
    56
    9
    10
    123
    14
    61
    16
    51
    37
        Diarrhea - Severe
    0
    0
    4
    0
    0
    7
    1
    4
    1
    5
    1
        Irritability - Any
    53
    53
    218
    29
    23
    289
    103
    271
    62
    130
    74
        Irritability - Severe
    2
    2
    6
    1
    2
    3
    1
    8
    4
    5
    0
        Persistent Crying - Any
    21
    21
    99
    7
    12
    134
    55
    120
    24
    52
    28
        Persistent Crying - Severe
    0
    0
    6
    0
    1
    2
    1
    6
    1
    0
    0
        Rash - Any
    8
    4
    23
    3
    1
    65
    12
    31
    5
    20
    17
        Rash - Severe
    1
    1
    2
    2
    0
    36
    3
    3
    3
    8
    10
        Sleepiness - Any
    38
    29
    111
    18
    15
    211
    50
    149
    22
    81
    53
        Sleepiness - Severe
    0
    1
    3
    0
    0
    3
    3
    3
    1
    1
    2
        Vomiting - Any
    6
    4
    21
    3
    5
    82
    11
    27
    8
    35
    12
        Vomiting - Severe
    0
    0
    1
    0
    0
    4
    0
    1
    0
    3
    0
        Analgesic / Antipyretic medication used
    60
    56
    260
    48
    43
    406
    120
    320
    78
    204
    87
    No statistical analyses for this end point

    Secondary: 39. Number of Subjects With Solicited Local and Systemic Reactions Post First Vaccination – Toddler Series

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    End point title
    		 39. Number of Subjects With Solicited Local and Systemic Reactions Post First Vaccination – Toddler Series [78]
    End point description
    End point type
    Secondary
    End point timeframe
    7 days post vaccination
    Notes
    [78] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US1B (MenACWY-CRM + Infant Vaccines) US4B (Infant Vaccines Only) US4C (Infant Vaccines Only) LA1A (MenACWY-CRM + Infant Vaccines) LA1B (MenACWY-CRM + Infant Vaccines) LA3A (MenACWY-CRM + Infant Vaccines) LA3B (MenACWY-CRM + Infant Vaccines) LA5 (MenACWY-CRM + Infant Vaccines) LA6B (Infant Vaccines Only) LA6C (Infant Vaccines Only) US1A + US3 Safety Set US2+US4A Safety Set LA2+LA4+LA6A Safety Set
    Number of subjects analysed
    120
    59
    179
    145
    143
    142
    137
    1275
    160
    175
    704
    136
    564
    Units: Subjects
    number (not applicable)
        Erythema (mm) - Any
    7
    9
    28
    36
    17
    36
    19
    309
    24
    52
    81
    18
    166
        Erythema (mm) - Severe
    0
    0
    1
    0
    1
    1
    1
    0
    0
    7
    2
    1
    2
        Induration (mm) - Any
    1
    3
    14
    32
    9
    33
    16
    84
    5
    35
    44
    12
    72
        Induration (mm) - Severe
    0
    0
    0
    0
    1
    1
    1
    0
    0
    5
    0
    0
    1
        Tenderness - Any
    16
    10
    38
    35
    21
    36
    18
    392
    34
    45
    177
    38
    184
        Tenderness - Severe
    0
    1
    1
    6
    1
    2
    2
    8
    0
    5
    2
    0
    2
        Body Temp. ( >= 38° C )
    5
    0
    5
    16
    5
    4
    2
    188
    7
    8
    49
    12
    84
        Change in Eating Habits - Any
    9
    5
    14
    10
    4
    6
    6
    138
    9
    17
    101
    20
    56
        Change in Eating Habits - Severe
    0
    0
    1
    1
    1
    1
    0
    5
    0
    0
    7
    1
    4
        Diarrhea - Any
    8
    5
    13
    9
    4
    8
    2
    123
    6
    12
    61
    16
    51
        Diarrhea - Severe
    0
    2
    1
    0
    0
    0
    1
    7
    0
    0
    4
    1
    5
        Irritability - Any
    39
    17
    52
    29
    10
    13
    9
    289
    25
    28
    271
    62
    130
        Irritability - Severe
    1
    1
    1
    1
    0
    0
    0
    3
    1
    0
    8
    4
    5
        Persistent Crying - Any
    16
    10
    17
    7
    5
    4
    5
    134
    9
    15
    120
    24
    52
        Persistent Crying - Severe
    0
    1
    1
    0
    0
    0
    0
    2
    1
    0
    6
    1
    0
        Rash - Any
    1
    2
    5
    3
    1
    2
    1
    65
    2
    2
    31
    5
    20
        Rash - Severe
    0
    0
    2
    2
    1
    2
    0
    36
    0
    1
    3
    3
    8
        Sleepiness - Any
    25
    6
    21
    18
    3
    6
    7
    211
    14
    20
    149
    22
    81
        Sleepiness - Severe
    1
    0
    0
    0
    1
    0
    0
    3
    1
    1
    3
    1
    1
        Vomiting - Any
    2
    2
    6
    3
    0
    1
    3
    82
    4
    3
    27
    8
    35
        Vomiting - Severe
    0
    0
    0
    0
    0
    0
    0
    4
    0
    0
    1
    0
    3
        Analgesic / Antipyretic medication used
    37
    16
    45
    48
    15
    20
    8
    406
    14
    34
    320
    77
    204
    No statistical analyses for this end point

    Secondary: 40. Number of Subjects With Solicited Local and Systemic Reactions Post Second Vaccination – Toddler Series

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    End point title
    		 40. Number of Subjects With Solicited Local and Systemic Reactions Post Second Vaccination – Toddler Series [79]
    End point description
    End point type
    Secondary
    End point timeframe
    7 days post vaccination
    Notes
    [79] - 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: No statistical analysis is associated to this Endpoint. Analyses were run descriptively.
    End point values
    		 US4B (Infant Vaccines Only) LA6B (Infant Vaccines Only) US2+US4A Safety Set LA2+LA4+LA6A Safety Set
    Number of subjects analysed
    55
    153
    120
    539
    Units: Subjects
    number (not applicable)
        Erythema (mm) - Any
    6
    28
    14
    143
        Erythema (mm) - Severe
    1
    0
    0
    2
        Induration (mm) - Any
    2
    2
    10
    51
        Induration (mm) - Severe
    1
    0
    0
    1
        Tenderness - Any
    16
    33
    19
    128
        Tenderness - Severe
    0
    1
    0
    5
        Body Temp. ( >= 38° C )
    1
    15
    5
    30
        Change in Eating Habits - Any
    2
    11
    7
    18
        Change in Eating Habits - Severe
    0
    1
    0
    0
        Diarrhea - Any
    3
    9
    4
    28
        Diarrhea - Severe
    0
    0
    1
    1
        Irritability - Any
    22
    32
    31
    71
        Irritability - Severe
    0
    1
    0
    2
        Persistent Crying - Any
    10
    6
    9
    37
        Persistent Crying - Severe
    0
    2
    0
    3
        Rash - Any
    1
    3
    4
    9
        Rash - Severe
    0
    3
    0
    4
        Sleepiness - Any
    8
    12
    12
    36
        Sleepiness - Severe
    0
    2
    0
    1
        Vomiting - Any
    2
    7
    5
    12
        Vomiting - Severe
    0
    0
    0
    0
        Analgesic / Antipyretic medication used
    14
    21
    40
    85
    No statistical analyses for this end point

    Secondary: 41. Number of Subjects With Solicited Local and Systemic Reactions Post First Vaccination – Infant Series

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    End point title
    		 41. Number of Subjects With Solicited Local and Systemic Reactions Post First Vaccination – Infant Series
    End point description
    End point type
    Secondary
    End point timeframe
    7 days post vaccination
    End point values
    		 US1+US3 Safety Set US2+US4 Safety Set LA3+LA5 Safety Set LA4+LA6 Safety Set
    Number of subjects analysed
    989
    503
    1724
    859
    Units: Subjects
    number (not applicable)
        Erythema (mm) - Any
    93
    77
    628
    338
        Erythema (mm) - Severe
    0
    6
    2
    5
        Induration (mm) - Any
    85
    69
    321
    179
        Induration (mm) - Severe
    0
    1
    2
    0
        Tenderness - Any
    464
    230
    1086
    596
        Tenderness - Severe
    32
    25
    114
    94
        Body Temp. ( >= 38° C )
    51
    28
    229
    102
        Change in Eating Habits - Any
    259
    130
    294
    143
        Change in Eating Habits - Severe
    10
    3
    6
    5
        Diarrhea - Any
    154
    63
    266
    118
        Diarrhea - Severe
    5
    2
    3
    2
        Irritability - Any
    608
    307
    607
    299
        Irritability - Severe
    32
    16
    26
    4
        Persistent Crying - Any
    369
    174
    566
    301
        Persistent Crying - Severe
    14
    13
    40
    29
        Rash - Any
    31
    16
    110
    59
        Rash - Severe
    11
    6
    58
    27
        Sleepiness - Any
    541
    249
    820
    433
        Sleepiness - Severe
    19
    3
    27
    18
        Vomiting - Any
    100
    50
    244
    117
        Vomiting - Severe
    0
    1
    3
    2
        Analgesic / Antipyretic medication used
    672
    333
    1155
    590
    No statistical analyses for this end point

    Secondary: 42. Number of Subjects With Solicited Local and Systemic Reactions Post Second Vaccination – Infant Series

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    End point title
    		 42. Number of Subjects With Solicited Local and Systemic Reactions Post Second Vaccination – Infant Series
    End point description
    End point type
    Secondary
    End point timeframe
    7 days post vaccination
    End point values
    		 US1+US3 Safety Set US2+US4 Safety Set LA3+LA5 Safety Set LA4+LA6 Safety Set
    Number of subjects analysed
    936
    476
    1672
    824
    Units: Subjects
    number (not applicable)
        Erythema (mm) - Any
    108
    95
    675
    356
        Erythema (mm) - Severe
    0
    2
    0
    0
        Induration (mm) - Any
    77
    75
    267
    162
        Induration (mm) - Severe
    1
    3
    0
    0
        Tenderness - Any
    348
    193
    841
    460
        Tenderness - Severe
    14
    13
    62
    50
        Body Temp. ( >= 38° C )
    72
    43
    246
    135
        Change in Eating Habits - Any
    168
    84
    188
    102
        Change in Eating Habits - Severe
    3
    0
    9
    5
        Diarrhea - Any
    79
    46
    177
    104
        Diarrhea - Severe
    2
    3
    5
    1
        Irritability - Any
    505
    265
    496
    250
        Irritability - Severe
    16
    12
    16
    5
        Persistent Crying - Any
    261
    141
    336
    209
        Persistent Crying - Severe
    5
    4
    18
    11
        Rash - Any
    32
    17
    110
    48
        Rash - Severe
    10
    5
    57
    30
        Sleepiness - Any
    363
    178
    547
    263
        Sleepiness - Severe
    3
    3
    17
    8
        Vomiting - Any
    66
    34
    156
    85
        Vomiting - Severe
    0
    1
    4
    0
        Analgesic / Antipyretic medication used
    570
    297
    988
    491
    No statistical analyses for this end point

    Secondary: 43. Number of Subjects With Solicited Local and Systemic Reactions Post Third Vaccination – Infant Series

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    End point title
    		 43. Number of Subjects With Solicited Local and Systemic Reactions Post Third Vaccination – Infant Series
    End point description
    End point type
    Secondary
    End point timeframe
    7 days post vaccination
    End point values
    		 US1+US3 Safety Set US2+US4 Safety Set LA3+LA5 Safety Set LA4+LA6 Safety Set
    Number of subjects analysed
    910
    454
    1646
    826
    Units: Subjects
    number (not applicable)
        Erythema (mm) - Any
    126
    95
    549
    311
        Erythema (mm) - Severe
    0
    2
    2
    1
        Induration (mm) - Any
    89
    82
    189
    105
        Induration (mm) - Severe
    0
    3
    1
    0
        Tenderness - Any
    271
    137
    582
    356
        Tenderness - Severe
    1
    8
    23
    15
        Body Temp. ( >= 38° C )
    46
    34
    190
    115
        Change in Eating Habits - Any
    135
    57
    149
    75
        Change in Eating Habits - Severe
    3
    3
    6
    3
        Diarrhea - Any
    63
    35
    109
    69
        Diarrhea - Severe
    2
    1
    2
    3
        Irritability - Any
    416
    227
    373
    192
        Irritability - Severe
    6
    6
    7
    2
        Persistent Crying - Any
    189
    98
    208
    130
        Persistent Crying - Severe
    4
    4
    11
    2
        Rash - Any
    25
    12
    68
    30
        Rash - Severe
    7
    4
    32
    11
        Sleepiness - Any
    257
    130
    362
    181
        Sleepiness - Severe
    6
    1
    7
    3
        Vomiting - Any
    43
    29
    115
    64
        Vomiting - Severe
    0
    1
    2
    1
        Analgesic / Antipyretic medication used
    506
    274
    682
    393
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Throughout the study
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    12.1
    Reporting groups
    Reporting group title
    LA2+4+6AB
    Reporting group description
    		 Groups Infant Vaccines only (LA2, LA4, LA6A and LA6B) pooled. In all groups LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These infants either received: one dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months and a second dose of MenACWY at 15 months of age (LA2 and LA4), or received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months and one dose each of MenACWY at 12 and 15 months of age (LA6A); or one dose each of MenACWY at 13 and 15 months of age (LA6B).

    Reporting group title
    LA1+LA3+LA5
    Reporting group description
    		 Groups Men ACWY-CRM + Infant Vaccines (LA1, LA3 and LA5) pooled LA1 infants received MenACWY at 2 and 6 months of age; and DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These infants received at 12 months of age pneumococcal conjugate vaccine, HAV, and MMR-V and concomitant third dose of MenACWY (LA1A) or a third dose of MenACWY at 13 months of age (LA1B). LA 3 and LA5 infants received MenACWY, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. At 12 months of age these infants received pneumococcal conjugate vaccine, HAV, and MMR-V and received: 1. Fourth dose of MenACWY concomitantly with DTaP and Hib at 16 months of age (LA3A) 2. DTaP and Hib at 16 months and fourth dose of MenACWY at 17 months of age (LA3B). 3. Concomitantly the fourth dose of MenACWY (LA5).

    Reporting group title
    LA6C
    Reporting group description
    		 LA infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus, and pneumococcal conjugate vaccines, at 2, 4 and 6 months of age. These infants received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and one dose of MenACWY at 18 months of age.

    Reporting group title
    US2+US4A+US4B
    Reporting group description
    		 Groups Infant Vaccines only (US2, US4A, and US4B) pooled. In both groups US infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines at 2, 4 and 6 months of age. These infants received: 1. One dose of MenACWY concomitantly with pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months; and a second dose of MenACWY at 15 months of age ( US2 and US4A). 2. Concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months and one dose of MenACWY at 13 and a second dose of MenACWY at 15 months of age (US4B).

    Reporting group title
    US1+US3
    Reporting group description
    		 Groups MenACWY-CRM + Infant Vaccines (US1 +US3) pooled. US infants received MenACWY at 2, 4 and 6 months of age along with routine infant vaccines, DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccine. These infants either received a fourth dose of MenACWY concomitantly with pneumococcal, HAV, and MMR-V vaccines at 12 months of age (US1A and US3) or received pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months and a fourth dose of MenACWY at 13 months of age( US1B).

    Reporting group title
    US4C
    Reporting group description
    		 US infants received as part of routine infant vaccination schedule DTaP-IPV-HBV, Hib, rotavirus and pneumococcal conjugate vaccines, at 2, 4 and 6 months of age. These subjects received concomitant pneumococcal conjugate vaccine, HAV, and MMR-V at 12 months and one dose of MenACWY at 18 months of age.

    Serious adverse events
    		 LA2+4+6AB LA1+LA3+LA5 LA6C US2+US4A+US4B US1+US3 US4C
    Total subjects affected by serious adverse events
         subjects affected / exposed
    84 / 824 (10.19%)
    173 / 2026 (8.54%)
    12 / 183 (6.56%)
    18 / 301 (5.98%)
    58 / 995 (5.83%)
    14 / 203 (6.90%)
         number of deaths (all causes)
    0
    3
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ACUTE MYELOID LEUKAEMIA
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRAIN NEOPLASM
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    KAWASAKI'S DISEASE
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    INTESTINAL OPERATION
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    OEDEMA
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    5 / 824 (0.61%)
    5 / 2026 (0.25%)
    1 / 183 (0.55%)
    0 / 301 (0.00%)
    3 / 995 (0.30%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
    0 / 1
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    DRUG HYPERSENSITIVITY
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FOOD ALLERGY
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOGAMMAGLOBULINAEMIA
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    APNOEA
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ASTHMA
         subjects affected / exposed
    3 / 824 (0.36%)
    6 / 2026 (0.30%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRONCHIAL HYPERREACTIVITY
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRONCHOSPASM
         subjects affected / exposed
    2 / 824 (0.24%)
    5 / 2026 (0.25%)
    1 / 183 (0.55%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHOKING
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOXIA
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LARYNGOSPASM
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PULMONARY HYPERTENSION
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY DISORDER
         subjects affected / exposed
    0 / 824 (0.00%)
    2 / 2026 (0.10%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SLEEP APNOEA SYNDROME
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    STATUS ASTHMATICUS
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TACHYPNOEA
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    WHEEZING
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    2 / 995 (0.20%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    ACCIDENTAL DRUG INTAKE BY CHILD
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ACCIDENTAL EXPOSURE
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BURNS SECOND DEGREE
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FOREIGN BODY
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HEAD INJURY
         subjects affected / exposed
    0 / 824 (0.00%)
    2 / 2026 (0.10%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LIMB TRAUMATIC AMPUTATION
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RIB FRACTURE
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ROAD TRAFFIC ACCIDENT
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SKULL FRACTURE
         subjects affected / exposed
    0 / 824 (0.00%)
    2 / 2026 (0.10%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    THERMAL BURN
         subjects affected / exposed
    0 / 824 (0.00%)
    2 / 2026 (0.10%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TRAUMATIC BRAIN INJURY
         subjects affected / exposed
    0 / 824 (0.00%)
    2 / 2026 (0.10%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    UPPER LIMB FRACTURE
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FOREIGN BODY ASPIRATION
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    ATRIAL SEPTAL DEFECT
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FALLOT'S TETRALOGY
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOSPADIAS
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OPTIC NERVE HYPOPLASIA
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYLORIC STENOSIS
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    CYANOSIS
         subjects affected / exposed
    1 / 824 (0.12%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PULMONARY VALVE STENOSIS
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    COMPLEX PARTIAL SEIZURES
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CONVULSION
         subjects affected / exposed
    0 / 824 (0.00%)
    5 / 2026 (0.25%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    2 / 995 (0.20%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FEBRILE CONVULSION
         subjects affected / exposed
    4 / 824 (0.49%)
    13 / 2026 (0.64%)
    1 / 183 (0.55%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 4
    2 / 13
    0 / 1
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GRAND MAL CONVULSION
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PSYCHOMOTOR SKILLS IMPAIRED
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SUBARACHNOID HAEMORRHAGE
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TONIC CONVULSION
         subjects affected / exposed
    2 / 824 (0.24%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    IRON DEFICIENCY ANAEMIA
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    1 / 183 (0.55%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LYMPHADENITIS
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    HAEMATOTYMPANUM
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    BLEPHARITIS
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    DIARRHOEA
         subjects affected / exposed
    4 / 824 (0.49%)
    8 / 2026 (0.39%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 8
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIARRHOEA HAEMORRHAGIC
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTRITIS
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    2 / 824 (0.24%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HAEMATOCHEZIA
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INGUINAL HERNIA
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTUSSUSCEPTION
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERITONITIS
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    STOMATITIS
         subjects affected / exposed
    1 / 824 (0.12%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    3 / 824 (0.36%)
    4 / 2026 (0.20%)
    1 / 183 (0.55%)
    1 / 301 (0.33%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    RASH
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URTICARIA
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    NEPHROTIC SYNDROME
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    SYNOSTOSIS
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    ABSCESS LIMB
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ABSCESS NECK
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ACARODERMATITIS
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ABSCESS ORAL
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ACUTE SINUSITIS
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ARTHRITIS BACTERIAL
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BACTERAEMIA
         subjects affected / exposed
    0 / 824 (0.00%)
    2 / 2026 (0.10%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BACTERIAL DIARRHOEA
         subjects affected / exposed
    6 / 824 (0.73%)
    3 / 2026 (0.15%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BOTULISM
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRONCHIOLITIS
         subjects affected / exposed
    16 / 824 (1.94%)
    32 / 2026 (1.58%)
    6 / 183 (3.28%)
    3 / 301 (1.00%)
    10 / 995 (1.01%)
    2 / 203 (0.99%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 33
    0 / 7
    0 / 3
    0 / 10
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    1 / 824 (0.12%)
    6 / 2026 (0.30%)
    2 / 183 (1.09%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRONCHITIS VIRAL
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRONCHOPNEUMONIA
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CELLULITIS
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    1 / 183 (0.55%)
    0 / 301 (0.00%)
    3 / 995 (0.30%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CROUP INFECTIOUS
         subjects affected / exposed
    0 / 824 (0.00%)
    3 / 2026 (0.15%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DENGUE FEVER
         subjects affected / exposed
    2 / 824 (0.24%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ENTERITIS INFECTIOUS
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    EXANTHEMA SUBITUM
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FEBRILE INFECTION
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    4 / 824 (0.49%)
    14 / 2026 (0.69%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    2 / 995 (0.20%)
    2 / 203 (0.99%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 14
    0 / 0
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    IMPETIGO
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INFECTIOUS MONONUCLEOSIS
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INFLUENZA
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LUNG INFECTION
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OSTEOMYELITIS
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OTITIS MEDIA
         subjects affected / exposed
    4 / 824 (0.49%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OTITIS MEDIA ACUTE
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERIORBITAL CELLULITIS
         subjects affected / exposed
    2 / 824 (0.24%)
    2 / 2026 (0.10%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERTUSSIS
         subjects affected / exposed
    2 / 824 (0.24%)
    2 / 2026 (0.10%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PHARYNGITIS
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    9 / 824 (1.09%)
    37 / 2026 (1.83%)
    2 / 183 (1.09%)
    2 / 301 (0.66%)
    4 / 995 (0.40%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 37
    0 / 3
    0 / 2
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA BACTERIAL
         subjects affected / exposed
    2 / 824 (0.24%)
    5 / 2026 (0.25%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA PRIMARY ATYPICAL
         subjects affected / exposed
    0 / 824 (0.00%)
    2 / 2026 (0.10%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA RESPIRATORY SYNCYTIAL VIRAL
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA VIRAL
         subjects affected / exposed
    1 / 824 (0.12%)
    2 / 2026 (0.10%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY SYNCYTIAL VIRUS BRONCHIOLITIS
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    1 / 183 (0.55%)
    4 / 301 (1.33%)
    4 / 995 (0.40%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 4
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY SYNCYTIAL VIRUS INFECTION
         subjects affected / exposed
    0 / 824 (0.00%)
    2 / 2026 (0.10%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    3 / 995 (0.30%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY TRACT INFECTION VIRAL
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SINUSITIS
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    STAPHYLOCOCCAL ABSCESS
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    2 / 995 (0.20%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    STAPHYLOCOCCAL INFECTION
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    2 / 995 (0.20%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    STAPHYLOCOCCAL SKIN INFECTION
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SUBCUTANEOUS ABSCESS
         subjects affected / exposed
    0 / 824 (0.00%)
    4 / 2026 (0.20%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    8 / 824 (0.97%)
    9 / 2026 (0.44%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VARICELLA
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VIRAL DIARRHOEA
         subjects affected / exposed
    1 / 824 (0.12%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VIRAL INFECTION
         subjects affected / exposed
    2 / 824 (0.24%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VIRAL PHARYNGITIS
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VULVAL ABSCESS
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    1 / 995 (0.10%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROENTERITIS VIRAL
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    1 / 301 (0.33%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    COW'S MILK INTOLERANCE
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DEHYDRATION
         subjects affected / exposed
    1 / 824 (0.12%)
    1 / 2026 (0.05%)
    2 / 183 (1.09%)
    1 / 301 (0.33%)
    5 / 995 (0.50%)
    2 / 203 (0.99%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 1
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIABETES MELLITUS
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIABETIC KETOACIDOSIS
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOGLYCAEMIA
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPONATRAEMIA
         subjects affected / exposed
    0 / 824 (0.00%)
    1 / 2026 (0.05%)
    0 / 183 (0.00%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 LA2+4+6AB LA1+LA3+LA5 LA6C US2+US4A+US4B US1+US3 US4C
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    740 / 824 (89.81%)
    1853 / 2026 (91.46%)
    171 / 183 (93.44%)
    279 / 301 (92.69%)
    957 / 995 (96.18%)
    202 / 203 (99.51%)
    Nervous system disorders
    SOMNOLENCE
         subjects affected / exposed
    513 / 824 (62.26%)
    1198 / 2026 (59.13%)
    110 / 183 (60.11%)
    184 / 301 (61.13%)
    676 / 995 (67.94%)
    141 / 203 (69.46%)
         occurrences all number
    1119
    2412
    235
    391
    1513
    360
    General disorders and administration site conditions
    INJECTION SITE ERYTHEMA
         subjects affected / exposed
    548 / 824 (66.50%)
    1245 / 2026 (61.45%)
    117 / 183 (63.93%)
    108 / 301 (35.88%)
    280 / 995 (28.14%)
    100 / 203 (49.26%)
         occurrences all number
    1361
    2589
    262
    202
    440
    201
    INJECTION SITE INDURATION
         subjects affected / exposed
    333 / 824 (40.41%)
    745 / 2026 (36.77%)
    90 / 183 (49.18%)
    101 / 301 (33.55%)
    204 / 995 (20.50%)
    78 / 203 (38.42%)
         occurrences all number
    597
    1230
    197
    169
    332
    156
    INJECTION SITE PAIN
         subjects affected / exposed
    698 / 824 (84.71%)
    1592 / 2026 (78.58%)
    164 / 183 (89.62%)
    196 / 301 (65.12%)
    651 / 995 (65.43%)
    147 / 203 (72.41%)
         occurrences all number
    1765
    3532
    422
    433
    1350
    351
    MALAISE
         subjects affected / exposed
    73 / 824 (8.86%)
    136 / 2026 (6.71%)
    5 / 183 (2.73%)
    0 / 301 (0.00%)
    0 / 995 (0.00%)
    0 / 203 (0.00%)
         occurrences all number
    92
    178
    5
    0
    0
    0
    PYREXIA
         subjects affected / exposed
    341 / 824 (41.38%)
    748 / 2026 (36.92%)
    74 / 183 (40.44%)
    94 / 301 (31.23%)
    296 / 995 (29.75%)
    74 / 203 (36.45%)
         occurrences all number
    584
    1173
    115
    134
    442
    129
    CRYING
         subjects affected / exposed
    419 / 824 (50.85%)
    927 / 2026 (45.76%)
    98 / 183 (53.55%)
    154 / 301 (51.16%)
    558 / 995 (56.08%)
    124 / 203 (61.08%)
         occurrences all number
    749
    1560
    197
    329
    1124
    276
    Gastrointestinal disorders
    DIARRHOEA
         subjects affected / exposed
    287 / 824 (34.83%)
    597 / 2026 (29.47%)
    57 / 183 (31.15%)
    91 / 301 (30.23%)
    289 / 995 (29.05%)
    78 / 203 (38.42%)
         occurrences all number
    527
    1040
    114
    136
    521
    133
    FLATULENCE
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    8 / 301 (2.66%)
    23 / 995 (2.31%)
    12 / 203 (5.91%)
         occurrences all number
    0
    0
    0
    10
    29
    12
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    29 / 824 (3.52%)
    53 / 2026 (2.62%)
    1 / 183 (0.55%)
    11 / 301 (3.65%)
    49 / 995 (4.92%)
    12 / 203 (5.91%)
         occurrences all number
    30
    55
    1
    12
    51
    14
    TEETHING
         subjects affected / exposed
    2 / 824 (0.24%)
    11 / 2026 (0.54%)
    0 / 183 (0.00%)
    28 / 301 (9.30%)
    83 / 995 (8.34%)
    30 / 203 (14.78%)
         occurrences all number
    2
    13
    0
    40
    115
    41
    VOMITING
         subjects affected / exposed
    228 / 824 (27.67%)
    486 / 2026 (23.99%)
    39 / 183 (21.31%)
    69 / 301 (22.92%)
    217 / 995 (21.81%)
    61 / 203 (30.05%)
         occurrences all number
    365
    798
    66
    97
    326
    92
    Respiratory, thoracic and mediastinal disorders
    BRONCHOSPASM
         subjects affected / exposed
    7 / 824 (0.85%)
    38 / 2026 (1.88%)
    15 / 183 (8.20%)
    0 / 301 (0.00%)
    15 / 995 (1.51%)
    3 / 203 (1.48%)
         occurrences all number
    8
    58
    27
    0
    15
    3
    COUGH
         subjects affected / exposed
    24 / 824 (2.91%)
    41 / 2026 (2.02%)
    4 / 183 (2.19%)
    20 / 301 (6.64%)
    64 / 995 (6.43%)
    15 / 203 (7.39%)
         occurrences all number
    24
    41
    5
    24
    75
    18
    NASAL CONGESTION
         subjects affected / exposed
    1 / 824 (0.12%)
    6 / 2026 (0.30%)
    1 / 183 (0.55%)
    15 / 301 (4.98%)
    60 / 995 (6.03%)
    18 / 203 (8.87%)
         occurrences all number
    1
    8
    1
    16
    69
    18
    Skin and subcutaneous tissue disorders
    DERMATITIS ATOPIC
         subjects affected / exposed
    16 / 824 (1.94%)
    26 / 2026 (1.28%)
    1 / 183 (0.55%)
    9 / 301 (2.99%)
    29 / 995 (2.91%)
    13 / 203 (6.40%)
         occurrences all number
    18
    27
    1
    9
    29
    14
    DERMATITIS DIAPER
         subjects affected / exposed
    4 / 824 (0.49%)
    8 / 2026 (0.39%)
    0 / 183 (0.00%)
    21 / 301 (6.98%)
    62 / 995 (6.23%)
    13 / 203 (6.40%)
         occurrences all number
    5
    8
    0
    25
    74
    14
    ECZEMA
         subjects affected / exposed
    0 / 824 (0.00%)
    0 / 2026 (0.00%)
    0 / 183 (0.00%)
    32 / 301 (10.63%)
    105 / 995 (10.55%)
    21 / 203 (10.34%)
         occurrences all number
    0
    0
    0
    34
    109
    25
    RASH
         subjects affected / exposed
    136 / 824 (16.50%)
    323 / 2026 (15.94%)
    32 / 183 (17.49%)
    33 / 301 (10.96%)
    154 / 995 (15.48%)
    39 / 203 (19.21%)
         occurrences all number
    221
    500
    43
    52
    207
    59
    Psychiatric disorders
    IRRITABILITY
         subjects affected / exposed
    474 / 824 (57.52%)
    1120 / 2026 (55.28%)
    110 / 183 (60.11%)
    240 / 301 (79.73%)
    800 / 995 (80.40%)
    171 / 203 (84.24%)
         occurrences all number
    1080
    2329
    267
    714
    2293
    566
    EATING DISORDERS
         subjects affected / exposed
    263 / 824 (31.92%)
    607 / 2026 (29.96%)
    69 / 183 (37.70%)
    122 / 301 (40.53%)
    425 / 995 (42.71%)
    93 / 203 (45.81%)
         occurrences all number
    475
    991
    129
    196
    759
    183
    Infections and infestations
    CONJUNCTIVITIS
         subjects affected / exposed
    28 / 824 (3.40%)
    68 / 2026 (3.36%)
    9 / 183 (4.92%)
    30 / 301 (9.97%)
    93 / 995 (9.35%)
    29 / 203 (14.29%)
         occurrences all number
    31
    74
    10
    40
    123
    35
    BRONCHIOLITIS
         subjects affected / exposed
    52 / 824 (6.31%)
    180 / 2026 (8.88%)
    36 / 183 (19.67%)
    34 / 301 (11.30%)
    108 / 995 (10.85%)
    25 / 203 (12.32%)
         occurrences all number
    67
    211
    51
    45
    139
    26
    BRONCHITIS
         subjects affected / exposed
    95 / 824 (11.53%)
    219 / 2026 (10.81%)
    17 / 183 (9.29%)
    6 / 301 (1.99%)
    10 / 995 (1.01%)
    5 / 203 (2.46%)
         occurrences all number
    140
    297
    28
    7
    10
    7
    CROUP INFECTIOUS
         subjects affected / exposed
    1 / 824 (0.12%)
    2 / 2026 (0.10%)
    0 / 183 (0.00%)
    12 / 301 (3.99%)
    44 / 995 (4.42%)
    15 / 203 (7.39%)
         occurrences all number
    1
    2
    0
    12
    56
    16
    GASTROENTERITIS
         subjects affected / exposed
    35 / 824 (4.25%)
    48 / 2026 (2.37%)
    3 / 183 (1.64%)
    18 / 301 (5.98%)
    49 / 995 (4.92%)
    6 / 203 (2.96%)
         occurrences all number
    39
    51
    3
    19
    55
    6
    NASOPHARYNGITIS
         subjects affected / exposed
    192 / 824 (23.30%)
    375 / 2026 (18.51%)
    27 / 183 (14.75%)
    9 / 301 (2.99%)
    41 / 995 (4.12%)
    11 / 203 (5.42%)
         occurrences all number
    267
    486
    13
    9
    43
    12
    OTITIS MEDIA
         subjects affected / exposed
    17 / 824 (2.06%)
    26 / 2026 (1.28%)
    2 / 183 (1.09%)
    76 / 301 (25.25%)
    258 / 995 (25.93%)
    62 / 203 (30.54%)
         occurrences all number
    23
    27
    3
    112
    413
    96
    OTITIS MEDIA ACUTE
         subjects affected / exposed
    15 / 824 (1.82%)
    37 / 2026 (1.83%)
    7 / 183 (3.83%)
    15 / 301 (4.98%)
    42 / 995 (4.22%)
    13 / 203 (6.40%)
         occurrences all number
    17
    40
    7
    33
    66
    34
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    71 / 824 (8.62%)
    163 / 2026 (8.05%)
    5 / 183 (2.73%)
    0 / 301 (0.00%)
    2 / 995 (0.20%)
    0 / 203 (0.00%)
         occurrences all number
    86
    198
    10
    0
    2
    0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    4 / 824 (0.49%)
    16 / 2026 (0.79%)
    0 / 183 (0.00%)
    108 / 301 (35.88%)
    340 / 995 (34.17%)
    74 / 203 (36.45%)
         occurrences all number
    4
    16
    0
    159
    459
    103
    VIRAL INFECTION
         subjects affected / exposed
    28 / 824 (3.40%)
    44 / 2026 (2.17%)
    1 / 183 (0.55%)
    22 / 301 (7.31%)
    82 / 995 (8.24%)
    20 / 203 (9.85%)
         occurrences all number
    30
    44
    1
    24
    94
    23

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Apr 2007
    Inclusion of a second primary endpoint to assess the response to what was described initially as a “boost” dose of MenACWY
    03 Dec 2007
    Testing for MMR-V antigens was removed from the planned testing.
    27 May 2008
    Revision of the primary objective and endpoints for all serogroups to evaluate the percentage of subjects with hSBA ≥ 1:8 one month post-4th dose instead of one month post-3rd dose
    07 Aug 2008
    To require subjects in groups US4 and LA6 (receiving MenACWY for the first time at 13 months of age) to delay their MenACWY vaccination until 18 months of age in order to serve as a control for the 4-dose MenACWY groups up to 6 months post the final MenACWY dose.
    15 Jun 2009
    To provide an a additional concomitant vaccine (2nd dose of Hepatitis A vaccine) in the study.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/22094635
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