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    Clinical Trial Results:
    A Phase 3, randomized, open label, controlled multi center study to evaluate the safety and immunogenicity of 4 doses of MenACWY conjugate vaccine, administered concomitantly with routine vaccines, among infants aged 2 months

    Due to a system error, the data reported in v1 is not correct and has been removed from public view.
    Summary
    EudraCT number
    		 2014-005061-72
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    23 Nov 2011

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

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    V59_33
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01000311
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Vaccines and Diagnostics
    Sponsor organisation address
    350 Massachusetts Avenue, Cambridge, United States, 02139
    Public contact
    Posting Director, Novartis Vaccine, RegistryContactVaccinesUS@novartis.com
    Scientific contact
    Posting Director, Novartis Vaccine, RegistryContactVaccinesUS@novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    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
    09 Oct 2012
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Nov 2011
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the sufficiency of the immune response following 4 doses of MenACWY vaccine given at 2, 4, 6 and 12 months in healthy infants in terms of the percentages of subjects with an human Serum Bacteridal Assay (hSBA) ≥1:8 at 1 month post vaccination, for each of the four meningococcal vaccine serogroups.
    Protection of trial subjects
    This trial was conducted in accordance with the ethical principles that have their origin in the latest version of the Declaration of Helsinki accepted by the local authorities, and was consistent with Good Clinical Practises (GCPs) and the applicable regulatory requirement (s) for the country in which the trial was conducted, GCPs according to International Conference on Harmonisation (ICH) guidelines, and applicable Standard Operating Procedures (SOPs).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    19 Nov 2009
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 74
    Country: Number of subjects enrolled
    Canada: 6
    Country: Number of subjects enrolled
    United States: 449
    Worldwide total number of subjects
    529
    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)
    529
    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

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    Recruitment
    Recruitment details
    		 Subjects were enrolled from 42 sites in USA, 3 sites in Australia and 1 site in Canada

    Pre-assignment
    Screening details
    		 All enrolled subjects were included in the trial

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    The trial was designed as an open-label study; both the study personnel and the subject’s parent/legal guardian knew the vaccines being administered; however, randomization was done in a blinded manner. Laboratory staff were blinded to the study group allocation when processing the serologies.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MenACWY-CRM + Routine Vaccines
    Arm description
    		 Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as an infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal Group A, C, W135 and Y conjugate vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One 0.5 mL dose of MenACWY was administered by intramuscular injection in the anterolateral area of the thigh.

    Investigational medicinal product name
    Pentacel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Routine vaccines were administered to subjects according to manufacturer instructions.

    Investigational medicinal product name
    Prevnar
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Routine vaccines were administered to subjects according to manufacturer instructions

    Investigational medicinal product name
    HBV vaccine
    Investigational medicinal product code
    Other name
    Hepatitis B vaccine, Engerix-B, H-B-VAX II, RECOMBINAX, Pediarix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Routine vaccines were administered to subjects according to manufacturer instructions

    Investigational medicinal product name
    MMR
    Investigational medicinal product code
    Other name
    MEASLES, MUMPS, and RUBELLA VIRUS VACCINE
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Routine vaccines were administered to subjects according to manufacturer instructions.

    Arm title
    		 Routine Vaccines
    Arm description
    		 Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Pentacel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Routine vaccines were administered to subjects according to manufacturer instructions

    Investigational medicinal product name
    HBV vaccine
    Investigational medicinal product code
    Other name
    Hepatitis B vaccine, Engerix-B, H-B-VAX II, RECOMBINAX
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Routine vaccines were administered to subjects according to manufacturer instructions

    Investigational medicinal product name
    Prevnar
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Routine vaccines were administered to subjects according to manufacturer instructions.

    Investigational medicinal product name
    MMR
    Investigational medicinal product code
    Other name
    MEASLES, MUMPS, and RUBELLA VIRUS VACCINE
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Routine vaccines were administered to subjects according to manufacturer instructions.

    Number of subjects in period 1
    		MenACWY-CRM + Routine Vaccines Routine Vaccines
    Started
    258
    271
    Completed
    213
    201
    Not completed
    45
    70
         Consent withdrawn by subject
    16
    24
         Inappropriate enrollment
    2
    -
         Adverse event
    2
    5
         Lost to follow-up
    15
    24
         Administrative reason
    9
    15
         Protocol deviation
    1
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MenACWY-CRM + Routine Vaccines
    Reporting group description
    		 Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as an infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

    Reporting group title
    Routine Vaccines
    Reporting group description
    		 Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

    Reporting group values
    		 MenACWY-CRM + Routine Vaccines Routine Vaccines Total
    Number of subjects
    		 258 271 529
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: days
        arithmetic mean (standard deviation)
    		 64.7 ( 6.5 ) 65.4 ( 7.4 ) -
    Gender categorical
    Units: Subjects
        Female
    		 125 130 255
        Male
    		 133 141 274

    End points

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    End points reporting groups
    Reporting group title
    MenACWY-CRM + Routine Vaccines
    Reporting group description
    		 Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as an infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

    Reporting group title
    Routine Vaccines
    Reporting group description
    		 Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

    Subject analysis set title
    All Enrolled Set
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All subjects who have signed an informed consent, undergone screening procedures, and are randomized

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

    Subject analysis set title
    Exposed Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All enrolled subjects who actually receive a study vaccination.

    Subject analysis set title
    Per Protocol - Concomitant Infant
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All enrolled subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviation as defined prior to database lock.

    Subject analysis set title
    Per Protocol - Pertussis Infant
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All enrolled subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviation as defined prior to database lock.

    Subject analysis set title
    Per Protocol - Hepatitis B Infant
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All enrolled subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviation as defined prior to database lock.

    Subject analysis set title
    Per Protocol - MenACWY Infant
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All enrolled subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviation as defined prior to database lock.

    Subject analysis set title
    Per Protocol - Pneumococcal Toddler
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All enrolled subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviation as defined prior to database lock.

    Subject analysis set title
    Per Protocol - MenACWY Toddler
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All enrolled subjects who received all the relevant doses of vaccine correctly; provided evaluable serum samples at the relevant time points; had no major protocol deviation as defined prior to database lock.

    Primary: 1. Percentage of Subjects With human Serum Bactericidal Assay (hSBA) Titer ≥1:8 Against Serogroup A, C, W and Y One Month After Toddler Vaccination

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    End point title
    		 1. Percentage of Subjects With human Serum Bactericidal Assay (hSBA) Titer ≥1:8 Against Serogroup A, C, W and Y One Month After Toddler Vaccination
    End point description
    Immunogenicity was measured as the percentage of subjects who achieved hSBA titer ≥1:8 against meningococcal serogroup A, C, W and Y, evaluated by serum bactericidal assay using human complement, at baseline and one month after toddler vaccination administered at 12 months of age. The immune response was considered sufficient if the lower limit of the two-sided 95% confidence intervals (CIs) for the percentage of subjects with hSBA titer ≥1:8, at one month after toddler vaccination, was greater than 85% for the serogroup C, W, or Y and greater than 80% for the serogroup A. Analysis was done on the per-protocol (PP) toddler dataset for MenACWY-CRM.
    End point type
    Primary
    End point timeframe
    Baseline and one month after toddler dose (month 13).
    End point values
    		 MenACWY-CRM + Routine Vaccines Routine Vaccines
    Number of subjects analysed
    170
    178
    Units: percentage of subjects
    number (confidence interval 95%)
        Serogroup A - Baseline (N=170,178)
    7 (4 to 12)
    2 (0 to 5)
        Serogroup A - Post-4th dose (N=168,175)
    89 (83 to 93)
    2 (0 to 5)
        Serogroup C - Baseline (N=166,174)
    37 (30 to 45)
    2 (1 to 6)
        Serogroup C - Post-4th dose (N=156,171)
    95 (90 to 98)
    2 (1 to 6)
        Serogroup W - Baseline (N=152,164)
    70 (62 to 77)
    5 (2 to 9)
        Serogroup W - Post-4th dose (N=153,165)
    97 (93 to 99)
    7 (3 to 12)
        Serogroup Y - Baseline (N=144,150)
    53 (45 to 61)
    3 (1 to 6)
        Serogroup Y - Post-4th dose (N=153,159)
    96 (92 to 99)
    1 (0 to 4)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    The sufficiency of the immune response following 4 doses of MenACWY vaccine given at 2, 4, 6 and 12 months in healthy infants was assessed in terms of the percentages of subjects with an hSBA ≥1:8 against serogroup A at 1 month post 4th vaccination.
    Comparison groups
    Routine Vaccines v MenACWY-CRM + Routine Vaccines
    Number of subjects included in analysis
    348
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    Parameter type
    		 lower limit of the two-sided 95% CI
    Point estimate
    89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 83
         upper limit
    		 93
    Notes
    [1] - Success criterion: The lower limit of the two-sided 95% CI for the percentage of subjects with hSBA ≥1:8, at 1 month after the fourth dose, to be greater than 80% for serogroup A.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    The sufficiency of the immune response following 4 doses of MenACWY vaccine given at 2, 4, 6 and 12 months in healthy infants was assessed in terms of the percentages of subjects with an hSBA ≥1:8 against serogroup C at 1 month post 4th vaccination.
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    348
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 lower limit of the two-sided 95% CI
    Point estimate
    95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 90
         upper limit
    		 98
    Notes
    [2] - Success criterion: The lower limit of the two-sided 95% CI for the percentage of subjects with hSBA ≥1:8, at 1 month after the fourth dose, to be greater than 85% for serogroup C.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    The sufficiency of the immune response following 4 doses of MenACWY vaccine given at 2, 4, 6 and 12 months in healthy infants was assessed in terms of the percentages of subjects with an hSBA ≥1:8 against serogroup W at 1 month post 4th vaccination.
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    348
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    Method
    Parameter type
    		 lower limit of the two-sided 95% CI
    Point estimate
    97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 93
         upper limit
    		 99
    Notes
    [3] - Success criterion: The lower limit of the two-sided 95% CI for the percentage of subjects with hSBA ≥1:8, at 1 month after the fourth dose, to be greater than 85% for serogroup W.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    The sufficiency of the immune response following 4 doses of MenACWY vaccine given at 2, 4, 6 and 12 months in healthy infants was assessed in terms of the percentages of subjects with an hSBA ≥1:8 against serogroup Y at 1 month post 4th vaccination.
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    348
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    Method
    Parameter type
    		 lower limit of the two-sided 95% CI
    Point estimate
    96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 92
         upper limit
    		 99
    Notes
    [4] - Success criterion: The lower limit of the two-sided 95% CI for the percentage of subjects with hSBA ≥1:8, at 1 month after the fourth dose, to be greater than 85% for serogroup Y.

    Secondary: 2.hSBA Geometric Mean Titers (GMTs) Against Serogroup A, C, W and Y One Month After Toddler Vaccination

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    End point title
    		 2.hSBA Geometric Mean Titers (GMTs) Against Serogroup A, C, W and Y One Month After Toddler Vaccination
    End point description
    Immunogenicity was measured as the hSBA GMTs directed against meningococcal serogroup A, C, W and Y, at baseline and one month after toddler vaccination administered at 12 months of age. Analysis was performed on the PP toddler dataset for MenACWY-CRM vaccination
    End point type
    Secondary
    End point timeframe
    Baseline and one month after toddler vaccination (month 13)
    End point values
    		 MenACWY-CRM + Routine Vaccines Routine Vaccines
    Number of subjects analysed
    168
    175
    Units: Titers
    geometric mean (confidence interval 95%)
        Serogroup A - Baseline (N=139,145)
    2.07 (1.98 to 2.16)
    2.01 (1.99 to 2.03)
        Serogroup A - Post-4th dose (N=168,175)
    54 (44 to 67)
    1.87 (1.55 to 2.27)
        Serogroup C - Baseline (N=126,136)
    2.49 (2.2 to 2.83)
    2.44 (2.2 to 2.7)
        Serogroup C - Post-4th dose (N=156,171)
    135 (107 to 171)
    1.94 (1.56 to 2.4)
        Serogroup W - Baseline (N=113,126)
    2.99 (2.49 to 3.6)
    2.97 (2.52 to 3.51)
        Serogroup W - Post-4th dose (N=153,165)
    215 (167 to 277)
    2.15 (1.77 to 2.6)
        Serogroup Y - Baseline (N=108,113)
    2.43 (2.19 to 2.71)
    2.32 (2.13 to 2.52)
        Serogroup Y - Post-4th dose (N=153,159)
    185 (148 to 233)
    1.89 (1.56 to 2.29)
    No statistical analyses for this end point

    Secondary: 3. Percentage of Subjects With hSBA Titers ≥1:8 and Four-Fold Increase in hSBA Titers Against Serogroup A, C, W and Y One Month After Three Doses Infant Series Vaccination

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    End point title
    		 3. Percentage of Subjects With hSBA Titers ≥1:8 and Four-Fold Increase in hSBA Titers Against Serogroup A, C, W and Y One Month After Three Doses Infant Series Vaccination
    End point description
    Immunogenicity was measured as the percentage of subjects with hSBA titers ≥1:8 against meningococcal serogroup A, C, W and Y, at baseline and one month after three infant doses of vaccines administered at 2, 4 and 6 months of age. Percentage of subjects who achieved at least four-fold rise in hSBA titers against serogroup A, C, W and Y was measured one month after three doses of infant series vaccination. Analysis was performed on the PP dataset of MenACWY-CRM infant vaccination series.
    End point type
    Secondary
    End point timeframe
    Baseline and one month after three doses of infant vaccination
    End point values
    		 MenACWY-CRM + Routine Vaccines Routine Vaccines
    Number of subjects analysed
    202
    208
    Units: Percentage of subjects
    number (confidence interval 95%)
        Serogroup A - hSBA ≥1:8-Baseline (N=170,178)
    2 (0 to 5)
    1 (0.014 to 3)
        Serogroup A - hSBA ≥1:8 -Post-3rd dose(N=202,208)
    76 (69 to 81)
    1 (0 to 4)
        Serogroup C - hSBA ≥1:8 -Baseline(N=166,174)
    7 (3 to 12)
    7 (4 to 12)
        Serogroup C - hSBA ≥1:8 -Post-3rd dose(N=199,206)
    94 (90 to 97)
    1 (0 to 4)
        Serogroup W - hSBA ≥1:8 -Baseline(N=152,164)
    13 (8 to 20)
    15 (10 to 21)
        Serogroup W - hSBA ≥1:8 -Post-3rd dose(N=194,202)
    98 (95 to 99)
    3 (1 to 7)
        Serogroup Y - hSBA ≥1:8 -Baseline(N=144,150)
    8 (4 to 13)
    4 (1 to 9)
        Serogroup Y - hSBA ≥1:8 -Post-3rd dose(N=188,196)
    94 (89 to 97)
    3 (1 to 6)
        Serogroup A - 4-fold rise-Post-3rd dose(N=170,177)
    78 (71 to 84)
    2 (0 to 5)
        Serogroup C - 4-fold rise-Post-3rd dose(N=164,171)
    94 (89 to 97)
    1 (0 to 4)
        Serogroup W - 4-fold rise-Post-3rd dose(N=147,158)
    93 (87 to 96)
    2 (0 to 5)
        Serogroup Y -4-fold rise-Post-3rd dose(N=135,142)
    93 (87 to 96)
    2 (0 to 6)
    No statistical analyses for this end point

    Secondary: 4. hSBA Geometric Mean Titers (GMTs) Against Serogroup A, C, W and Y One Month After Three Doses Infant Series Vaccination

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    End point title
    		 4. hSBA Geometric Mean Titers (GMTs) Against Serogroup A, C, W and Y One Month After Three Doses Infant Series Vaccination
    End point description
    Immunogenicity was measured as the hSBA GMTs directed against meningococcal serogroups A, C, W and Y before (baseline) and one month after three doses of infant series vaccination administered at 2, 4 and 6 months of age. Analysis was performed on the PP dataset of MenACWY-CRM infant vaccination series.
    End point type
    Secondary
    End point timeframe
    Baseline and one month after three doses of infant series vaccination
    End point values
    		 MenACWY-CRM + Routine Vaccines Routine Vaccines
    Number of subjects analysed
    202
    209
    Units: Titers
    geometric mean (confidence interval 95%)
        Serogroup A - Baseline (N=170,178)
    2.09 (2 to 2.18)
    2.05 (1.98 to 2.12)
        Serogroup A - Post-3rd dose (N=202,208)
    21 (17 to 26)
    2.08 (1.99 to 2.17)
        Serogroup C - Baseline (N=166,174)
    2.49 (2.25 to 2.76)
    2.39 (2.18 to 2.61)
        Serogroup C - Post-3rd dose (N=199,206)
    74 (62 to 87)
    1.94 (1.64 to 2.3)
        Serogroup W - Baseline (N=152,164)
    2.94 (2.52 to 3.43)
    2.98 (2.58 to 3.45)
        Serogroup W - Post-3rd dose (N=194,202)
    79 (67 to 92)
    1.94 (1.68 to 2.24)
        Serogroup Y - Baseline (N=144,150)
    2.52 (2.28 to 2.77)
    2.26 (2.12 to 2.41)
        Serogroup Y - Post-3rd dose (N=188,196)
    51 (43 to 61)
    2.13 (2.02 to 2.25)
    No statistical analyses for this end point

    Secondary: 5. Percentage of Subjects With Immune Response to Routine Concomitant Vaccinations One Month After Infant Series, When Routine Vaccines Are Administered With MenACWY-CRM Compared With When Routine Vaccines Are Given Alone

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    End point title
    		 5. Percentage of Subjects With Immune Response to Routine Concomitant Vaccinations One Month After Infant Series, When Routine Vaccines Are Administered With MenACWY-CRM Compared With When Routine Vaccines Are Given Alone
    End point description
    The percentages of subjects with pre-specified cut-off limit of ≥ 0.1 IU/mL (Diphtheria and Tetanus); ≥ 0.15 μg/mL (Hib); ≥ 0.35 μg/mL (Pneumococcal antigens, PnC); and ≥ 10 mIU/mL (Hepatitis B) was evaluated using enzyme-linked immunosorbent assay (ELISA) at one month after three doses of infant series vaccination administered at 2, 4 and 6 months of age. The percentage of subjects with immune response against pertussis antigens (PT, FHA, Pertactin, FIM) (initially seronegative infants, ≥4 times the lower limit of quantification (LLQ); initially seropositive infants, at least 4 times prevaccination concentration) was measured by ELISA and percentage of subjects with titer ≥1:8 (Polio types 1,2,3) by neutralization test (NT) one month after three doses of infant series vaccination administered at 2, 4 and 6 months of age. Analysis was performed on the PP concomitant infant population.
    End point type
    Secondary
    End point timeframe
    One month after three doses of infant series vaccination
    End point values
    		 MenACWY-CRM + Routine Vaccines Routine Vaccines
    Number of subjects analysed
    207
    218
    Units: Percentage of subjects
    number (confidence interval 95%)
        Diphtheria (≥0.1 IU/mL)
    99 (96 to 100)
    99 (96 to 100)
        Tetanus (≥0.1 IU/mL)
    97 (94 to 99)
    97 (93 to 99)
        PT (N=185,191)
    77 (71 to 83)
    81 (75 to 86)
        FHA (N=185,191)
    70 (63 to 76)
    65 (58 to 72)
        Pertactin (N=185,191)
    73 (66 to 79)
    73 (66 to 79)
        FIM (N=185,191)
    74 (67 to 80)
    76 (69 to 82)
        Polio Type 1 - ≥1:8 (N=115,113)
    99 (95 to 100)
    98 (94 to 100)
        Polio Type 2 - ≥1:8 (N=185,179)
    100 (98 to 100)
    99 (97 to 100)
        Polio Type 3 - ≥1:8 (N=164,162)
    99 (97 to 100)
    100 (98 to 100)
        Hepatitis B - ≥10 mIU/mL (N=138,148)
    96 (92 to 99)
    97 (92 to 99)
        PRP-Hib - ≥0.15 μg/mL (N=187,194)
    95 (90 to 97)
    89 (84 to 93)
        PnC 4 - ≥0.35 μg/mL (N=183,178)
    99 (96 to 100)
    98 (94 to 99)
        PnC 6B - ≥0.35 μg/mL (N=183,178)
    86 (80 to 91)
    90 (84 to 94)
        PnC 9V - ≥0.35 μg/mL (N=183,178)
    91 (86 to 95)
    94 (90 to 97)
        PnC 14 - ≥0.35 μg/mL (N=183,178)
    99 (96 to 100)
    99 (96 to 100)
        PnC 18C - ≥0.35 μg/mL (N=183,178)
    95 (90 to 97)
    97 (94 to 99)
        PnC 19F - ≥0.35 μg/mL (N=183,178)
    100 (98 to 100)
    97 (93 to 99)
        PnC 23F - ≥0.35 μg/mL (N=183,178)
    89 (83 to 93)
    94 (89 to 97)
    Statistical analysis title
    		 statistical analysis 1
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to diphtheria toxin, when DTaP vaccine is given with MenACWY-CRM compared with when DTaP vaccine is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 2.6
    Notes
    [5] - Success criterion: The immune response to diphtheria toxin, when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to tetanus toxin, when DTaP vaccine is given with MenACWY-CRM compared with when DTaP vaccine is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.3
         upper limit
    		 3.9
    Notes
    [6] - Success criterion: The immune response to tetanus toxin, when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pertussis toxin (PT), when DTaP vaccine is given with MenACWY-CRM compared with when DTaP vaccine is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [7]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    -4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.1
         upper limit
    		 4.3
    Notes
    [7] - Success criterion: The immune response to pertussis toxin (PT), when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pertussis FHA antigen, when DTaP vaccine is given with MenACWY-CRM compared with when DTaP vaccine is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.1
         upper limit
    		 13.6
    Notes
    [8] - Success criterion: The immune response to pertussis FHA antigen, when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pertussis pertactin antigen, when DTaP vaccine is given with MenACWY-CRM compared with when DTaP vaccine is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [9]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.8
         upper limit
    		 9.1
    Notes
    [9] - Success criterion: The immune response to pertussis pertactin antigen, when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pertussis FIM antigen, when DTaP vaccine is given with MenACWY-CRM compared with when DTaP vaccine is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [10]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.6
         upper limit
    		 6.8
    Notes
    [10] - Success criterion: The immune response to pertussis FIM antigen, when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to hepatitis B antigen, when hepatitis B vaccine is given with MenACWY-CRM compared with when hepatitis B vaccine is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [11]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.2
         upper limit
    		 4.5
    Notes
    [11] - Success criterion: The immune response to hepatitis B antigen, when hepatitis B vaccine is given concomitantly with MenACWY-CRM, was considered non-inferior to that of hepatitis B vaccine given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to Hib antigen, when Hib vaccine is given with MenACWY-CRM compared with when Hib vaccine is given alone.
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [12]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 11.2
    Notes
    [12] - Success criterion: The immune response to Hib vaccine, when given concomitantly with MenACWY-CRM, was considered non-inferior to that of Hib vaccine given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
    Statistical analysis title
    		 Statistical analysis 9
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to polio antigen (Type 1), when IPV routine is given with MenACWY-CRM, compared with when IPV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [13]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.1
         upper limit
    		 5.4
    Notes
    [13] - Success criterion: The immune response to polio antigen (Type 1), when IPV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of IPV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -5%.
    Statistical analysis title
    		 Statistical analysis 10
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to polio antigen (Type 2), when IPV routine is given with MenACWY-CRM, compared with when IPV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [14]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 3
    Notes
    [14] - Success criterion: The immune response to polio antigen (Type 2), when IPV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of IPV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -5%.
    Statistical analysis title
    		 Statistical analysis 11
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to polio antigen (Type 3), when IPV routine is given with MenACWY-CRM, compared with when IPV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [15]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.3
         upper limit
    		 1.7
    Notes
    [15] - Success criterion: The immune response to polio antigen (Type 3), when IPV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of IPV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -5%.
    Statistical analysis title
    		 Statistical analysis 12
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pneumococcal PnC 4 antigen, when PCV is given with MenACWY-CRM, compared with when PCV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [16]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 4.6
    Notes
    [16] - Success criterion: The immune response to pneumococcal PnC 4 antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
    Statistical analysis title
    		 Statistical analysis 13
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pneumococcal PnC 6B antigen, when Pneumococcal Veccine (PCV) is given with MenACWY-CRM, compared with when PCV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [17]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    -4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.3
         upper limit
    		 3.2
    Notes
    [17] - Success criterion: The immune response to pneumococcal PnC 6B antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
    Statistical analysis title
    		 Statistical analysis 14
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pneumococcal PnC 9V antigen, when Pneumococcal Veccine (PCV) is given with MenACWY-CRM, compared with when PCV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [18]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    -3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.7
         upper limit
    		 2.3
    Notes
    [18] - Success criterion: The immune response to pneumococcal PnC 9V antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
    Statistical analysis title
    		 Statistical analysis 15
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pneumococcal PnC 14 antigen, when Pneumococcal Veccine (PCV) is given with MenACWY-CRM, compared with when PCV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [19]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.8
         upper limit
    		 3
    Notes
    [19] - Success criterion: The immune response to pneumococcal PnC 14 antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
    Statistical analysis title
    		 Statistical analysis 16
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pneumococcal PnC 18C antigen, when Pneumococcal Vaccine (PCV) is given with MenACWY-CRM, compared with when PCV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [20]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    -3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.3
         upper limit
    		 1.6
    Notes
    [20] - Success criterion: The immune response to pneumococcal PnC 18C antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
    Statistical analysis title
    		 Statistical analysis 17
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pneumococcal PnC 19F antigen, when Pneumococcal Vaccine (PCV) is given with MenACWY-CRM, compared with when PCV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [21]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.3
         upper limit
    		 7.1
    Notes
    [21] - Success criterion: The immune response to pneumococcal PnC 19F antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
    Statistical analysis title
    		 Statistical analysis 18
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pneumococcal PnC 23F antigen, when Pneumococcal Veccine (PCV) is given with MenACWY-CRM, compared with when PCV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [22]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 vaccine group difference
    Point estimate
    -5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.4
         upper limit
    		 0.5
    Notes
    [22] - Success criterion: The immune response to pneumococcal PnC 23F antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.

    Secondary: 6. Geometric Mean Concentrations (GMCs) of Antibodies Against Routine Concomitant Vaccinations One Month After Infant Series, When Routine Vaccines Are Administered With MenACWY-CRM Compared With When Routine Vaccines Are Given Alone

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    End point title
    		 6. Geometric Mean Concentrations (GMCs) of Antibodies Against Routine Concomitant Vaccinations One Month After Infant Series, When Routine Vaccines Are Administered With MenACWY-CRM Compared With When Routine Vaccines Are Given Alone
    End point description
    The immune response was measured as the GMCs of antibodies directed against diphtheria, tetanus, pertussis (PT, FHA, Pertactin, FIM), hepatitis B, Hib, polio (type 1, 2 and 3) and pneumococcal (PnC 4, 6B, 9V, 14, 18C, 19F and 23F) antigens when routine vaccines are administered concomitantly with MenACWY-CRM compared with when routine vaccines are given alone, one month after three doses of infant series vaccination at 2, 4 and 6 months of age. Analysis was performed on the PP concomitant infants population.
    End point type
    Secondary
    End point timeframe
    One month after three doses of infant series vaccination
    End point values
    		 MenACWY-CRM + Routine Vaccines Routine Vaccines
    Number of subjects analysed
    207
    218
    Units: μg/mL
    geometric mean (confidence interval 95%)
        Diphtheria
    0.7 (0.63 to 0.78)
    0.85 (0.76 to 0.94)
        Tetanus
    0.8 (0.7 to 0.91)
    0.67 (0.59 to 0.76)
        PT (N=185,191)
    25 (21 to 30)
    24 (21 to 29)
        FHA (N=185,191)
    48 (43 to 54)
    47 (42 to 52)
        Pertactin (N=185,191)
    56 (47 to 65)
    54 (46 to 62)
        FIM (N=185,191)
    133 (113 to 157)
    122 (105 to 143)
        Polio Type 1 (N=115,113)
    149 (115 to 194)
    117 (89 to 152)
        Polio Type 2 (N=185,179)
    210 (178 to 246)
    185 (156 to 218)
        Polio Type 3 (N=164,162)
    457 (367 to 569)
    402 (321 to 504)
        Hepatitis B (N=138,148)
    394 (284 to 546)
    402 (289 to 558)
        Hib (N=187,194)
    3.75 (2.92 to 4.82)
    2.76 (2.16 to 3.53)
        PnC 4 (N=183,178)
    1.3 (1.16 to 1.46)
    1.45 (1.29 to 1.63)
        PnC 6B (N=183,178)
    1.42 (1.17 to 1.72)
    1.79 (1.47 to 2.18)
        PnC 9V (N=183,178)
    0.95 (0.84 to 1.08)
    1.2 (1.05 to 1.36)
        PnC 14 (N=183,178)
    6.31 (5.45 to 7.31)
    6.61 (5.69 to 7.68)
        PnC 18C (N=183,178)
    1.36 (1.2 to 1.55)
    1.42 (1.24 to 1.62)
        PnC 19F (N=183,178)
    1.84 (1.63 to 2.08)
    2.04 (1.8 to 2.32)
        PnC 23F (N=183,178)
    1.15 (0.99 to 1.35)
    1.33 (1.13 to 1.56)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pertussis toxin (PT), when DTaP vaccine is given with MenACWY-CRM compared with when DTaP vaccine is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [23]
    Method
    		 ANOVA
    Parameter type
    		 vaccine group ratio of GMCs
    Point estimate
    1.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 1.28
    Notes
    [23] - Success criterion: The immune response measured as GMC of antibodies to pertussis toxin (PT), when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the ratio of GMCs (GMC of MenACWY-CRM + Routine Vaccines group divided by GMC of Routine Vaccines group) was greater than 0.67
    Statistical analysis title
    		 Stastical analysis 2
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pertussis FHA antigen, when DTaP vaccine is given with MenACWY-CRM compared with when DTaP vaccine is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [24]
    Method
    		 ANOVA
    Parameter type
    		 vaccine group ratio of GMCs
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.19
    Notes
    [24] - Success criterion: The immune response measured as GMC of antibodies to pertussis FHA antigen, when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the ratio of GMCs (GMC of MenACWY-CRM + Routine Vaccines group divided by GMC of Routine Vaccines group) was greater than 0.67.
    Statistical analysis title
    		 Stastical analysis 3
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pertussis pertactin antigen, when DTaP vaccine is given with MenACWY-CRM compared with when DTaP vaccine is given alone
    Comparison groups
    Routine Vaccines v MenACWY-CRM + Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [25]
    Method
    		 ANOVA
    Parameter type
    		 vaccine group ratio of GMCs
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.28
    Notes
    [25] - Success criterion: The immune response measured as GMC of antibodies to pertussis pertactin antigen, when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the ratio of GMCs (GMC of MenACWY-CRM + Routine Vaccines group divided by GMC of Routine Vaccines group) was greater than 0.67.
    Statistical analysis title
    		 Stastical analysis 4
    Statistical analysis description
    To demonstrate the non-inferiority of immune response to pertussis FIM antigen, when DTaP vaccine is given with MenACWY-CRM compared with when DTaP vaccine is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    425
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [26]
    Method
    		 ANOVA
    Parameter type
    		 vaccine group ratio of GMCs
    Point estimate
    1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.35
    Notes
    [26] - Success criterion: The immune response measured as GMC of antibodies to pertussis FIM antigen, when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the ratio of GMCs (GMC of MenACWY-CRM + Routine Vaccines group divided by GMC of Routine Vaccines group) was greater than 0.67.

    Secondary: 7. GMCs of Antibodies Against Pneumococcal Antigens One Month After Toddler Vaccination With PCV Administered With MenACWY-CRM Compared With PCV Given Alone

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    End point title
    		 7. GMCs of Antibodies Against Pneumococcal Antigens One Month After Toddler Vaccination With PCV Administered With MenACWY-CRM Compared With PCV Given Alone
    End point description
    Immunogenicity was measured as the GMCs of anti-pneumococcal antibodies against pneumococcal antigens PnC 4, 6B, 9V, 14, 18C, 19F and 23F, one month after toddler dose of PCV at 12 months of age administered concomitantly with MenACWY-CRM compared with PCV given alone. Analysis was performed on the PP pneumococcal toddler population.
    End point type
    Secondary
    End point timeframe
    One month after PCV toddler vaccination
    End point values
    		 MenACWY-CRM + Routine Vaccines Routine Vaccines
    Number of subjects analysed
    161
    170
    Units: µg/mL
    geometric mean (confidence interval 95%)
        PnC 4
    1.57 (1.35 to 1.82)
    1.6 (1.39 to 1.85)
        PnC 6B
    5.92 (5.05 to 6.95)
    7.8 (6.69 to 9.09)
        PnC 9V
    1.67 (1.44 to 1.93)
    1.91 (1.66 to 2.19)
        PnC 14
    7.9 (6.73 to 9.28)
    7.61 (6.52 to 8.88)
        PnC 18C
    1.79 (1.55 to 2.08)
    1.8 (1.57 to 2.08)
        PnC 19F
    5.03 (4.36 to 5.82)
    5.68 (4.95 to 6.53)
        PnC 23F
    3.3 (2.8 to 3.89)
    3.91 (3.34 to 4.57)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    To demonstrate the non-inferiority of GMC of antibodies to pneumococcal PnC 4 antigen when PCV is given with MenACWY-CRM compared with when PCV is given alone
    Comparison groups
    Routine Vaccines v MenACWY-CRM + Routine Vaccines
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [27]
    Method
    		 ANOVA
    Parameter type
    		 vaccine group ratio of GMCs
    Point estimate
    0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 1.19
    Notes
    [27] - Success criterion: The immune response as GMC of antibodies to pneumococcal PnC 4 antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the ratio of GMCs (GMC of MenACWY-CRM + Prevnar group divided by GMC of Prevnar group) was greater than 0.50.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    To demonstrate the non-inferiority of GMC of antibodies to pneumococcal PnC 6B antigen when PCV is given with MenACWY-CRM compared with when PCV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [28]
    Method
    		 ANOVA
    Parameter type
    		 vaccine group ratio of GMCs
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 0.93
    Notes
    [28] - Success criterion: The immune response as GMC of antibodies to pneumococcal PnC 6B antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the ratio of GMCs (GMC of MenACWY-CRM + Prevnar group divided by GMC of Prevnar group) was greater than 0.50
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    To demonstrate the non-inferiority of GMC of antibodies to pneumococcal PnC 9V antigen when PCV is given with MenACWY-CRM compared with when PCV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [29]
    Method
    		 ANOVA
    Parameter type
    		 vaccine group ratio of GMCs
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.72
         upper limit
    		 1.06
    Notes
    [29] - Success criterion: The immune response as GMC of antibodies to pneumococcal PnC 9V antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the ratio of GMCs (GMC of MenACWY-CRM + Prevnar group divided by GMC of Prevnar group) was greater than 0.50.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    To demonstrate the non-inferiority of GMC of antibodies to pneumococcal PnC 14 antigen when PCV is given with MenACWY-CRM compared with when PCV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [30]
    Method
    		 ANOVA
    Parameter type
    		 vaccine group ratio of GMCs
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.28
    Notes
    [30] - Success criterion: The immune response as GMC of antibodies to pneumococcal PnC 14 antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the ratio of GMCs (GMC of MenACWY-CRM + Prevnar group divided by GMC of Prevnar group) was greater than 0.50.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    To demonstrate the non-inferiority of GMC of antibodies to pneumococcal PnC 18C antigen when PCV is given with MenACWY-CRM compared with when PCV is given alone.
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [31]
    Method
    		 ANOVA
    Parameter type
    		 vaccine group ratio of GMCs
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 1.2
    Notes
    [31] - Success criterion: The immune response as GMC of antibodies to pneumococcal PnC 18C antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the ratio of GMCs (GMC of MenACWY-CRM + Prevnar group divided by GMC of Prevnar group) was greater than 0.50.
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    To demonstrate the non-inferiority of GMC of antibodies to pneumococcal PnC 19F antigen when PCV is given with MenACWY-CRM compared with when PCV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [32]
    Method
    		 ANOVA
    Parameter type
    		 vaccine group ratio of GMCs
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.07
    Notes
    [32] - Success criterion: The immune response as GMC of antibodies to pneumococcal PnC 19F antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the ratio of GMCs (GMC of MenACWY-CRM + Prevnar group divided by GMC of Prevnar group) was greater than 0.50.
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    To demonstrate the non-inferiority of GMC of antibodies to pneumococcal PnC 23F antigen when PCV is given with MenACWY-CRM compared with when PCV is given alone
    Comparison groups
    MenACWY-CRM + Routine Vaccines v Routine Vaccines
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [33]
    Method
    		 ANOVA
    Parameter type
    		 vaccine group ratio of GMCs
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 1.04
    Notes
    [33] - Success criterion: The immune response as GMC of antibodies to pneumococcal PnC 23F antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the ratio of GMCs (GMC of MenACWY-CRM + Prevnar group divided by GMC of Prevnar group) was greater than 0.50.

    Secondary: 8. Percentage of Subjects With Anti-pneumococcal Antigen Antibodies ≥0.35 μg/mL One Month After Toddler Vaccination With PCV Administered With MenACWY-CRM Compared With PCV Given Alone

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    End point title
    		 8. Percentage of Subjects With Anti-pneumococcal Antigen Antibodies ≥0.35 μg/mL One Month After Toddler Vaccination With PCV Administered With MenACWY-CRM Compared With PCV Given Alone
    End point description
    The immune response was measured as the percentage of subjects with anti-pneumococcal antigen antibodies ≥0.35 μg/mL against pneumococcal antigens PnC 4, 6B, 9V, 14, 18C, 19F and 23F, one month after toddler dose of PCV at 12 months of age when administered concomitantly with MenACWY-CRM compared with PCV given alone. Analysis was performed on the PP pneumococcal toddler population.
    End point type
    Secondary
    End point timeframe
    One month after PCV toddler vaccination
    End point values
    		 MenACWY-CRM + Routine Vaccines Routine Vaccines
    Number of subjects analysed
    161
    170
    Units: Percentage of subjects
    number (confidence interval 95%)
        PnC 4
    93 (88 to 97)
    96 (92 to 98)
        PnC 6B
    99 (97 to 100)
    98 (95 to 100)
        PnC 9V
    97 (93 to 99)
    96 (92 to 98)
        PnC 14
    99 (96 to 100)
    99 (97 to 100)
        PnC 18C
    96 (92 to 99)
    98 (94 to 99)
        PnC 19F (N=161,169)
    99 (96 to 100)
    100 (98 to 100)
        PnC 23F
    99 (97 to 100)
    98 (94 to 99)
    No statistical analyses for this end point

    Secondary: 9. Antibody Persistence by Percentage of Subjects With hSBA Titers ≥1:8 Against Serogroup A, C, W and Y at 12 Months of Age Prior to Toddler Vaccination

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    End point title
    		 9. Antibody Persistence by Percentage of Subjects With hSBA Titers ≥1:8 Against Serogroup A, C, W and Y at 12 Months of Age Prior to Toddler Vaccination
    End point description
    The antibody persistence was measured as the percentage of subjects with hSBA titers ≥1:8 against meningococcal serogroup A, C, W and Y, at baseline and six months after three doses of infant series vaccination administered at 6 months (12 months of age), before administration of the toddler vaccination. Analysis was performed on the PP toddler dataset for MenACWY-CRM.
    End point type
    Secondary
    End point timeframe
    Baseline and six months after three doses of infant series vaccination
    End point values
    		 MenACWY-CRM + Routine Vaccines Routine Vaccines
    Number of subjects analysed
    170
    178
    Units: Percentage of subjects
    number (confidence interval 95%)
        Serogroup A - Baseline (N=139, 145)
    1 (0 to 5)
    0 (0 to 3)
        Serogroup A - 6 mo Post-3rd dose (N=168,175)
    7 (4 to 12)
    2 (0 to 5)
        Serogroup C - Baseline (N=126,136)
    7 (3 to 13)
    8 (4 to 14)
        Serogroup C - 6 mo Post-3rd dose (N=156,171)
    37 (30 to 45)
    2 (1 to 6)
        Serogroup W - Baseline (N=113,126)
    15 (9 to 23)
    15 (9 to 23)
        Serogroup W - 6 mo Post-3rd dose (N=153,165)
    70 (62 to 77)
    5 (2 to 9)
        Serogroup Y - Baseline (N=108,113)
    6 (3 to 13)
    5 (2 to 11)
        Serogroup Y - 6 mo Post-3rd dose (N=153,159)
    53 (45 to 61)
    3 (1 to 6)
    No statistical analyses for this end point

    Secondary: 10. Persistence of hSBA Geometric Mean Titers (GMTs) Against Serogroup A, C, W and Y, at 12 Months of Age, Prior to Toddler Vaccination

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    End point title
    		 10. Persistence of hSBA Geometric Mean Titers (GMTs) Against Serogroup A, C, W and Y, at 12 Months of Age, Prior to Toddler Vaccination
    End point description
    The antibody persistence was measured as the hSBA GMTs directed against meningococcal serogroup A, C, W and Y, at baseline and six months after third infant vaccination administered at 6 months (12 months of age), before administration of the toddler dose vaccination. Analysis was performed on the PP toddler dataset for MenACWY-CRM.
    End point type
    Secondary
    End point timeframe
    Baseline and six months after three doses of infant series vaccination
    End point values
    		 MenACWY-CRM + Routine Vaccines Routine Vaccines
    Number of subjects analysed
    170
    178
    Units: Titers
    geometric mean (confidence interval 95%)
        Serogroup A - Baseline (N=139, 145)
    2.07 (1.98 to 2.16)
    2.01 (1.99 to 2.03)
        Serogroup A - 6 mo Post-3rd dose (N=168,175)
    2.52 (2.26 to 2.82)
    2.12 (2 to 2.25)
        Serogroup C - Baseline (N=126,136)
    2.49 (2.2 to 2.83)
    2.44 (2.2 to 2.7)
        Serogroup C - 6 mo Post-3rd dose (N=156,171)
    5.98 (4.81 to 7.43)
    2.15 (2.02 to 2.3)
        Serogroup W - Baseline (N=113,126)
    2.99 (2.49 to 3.6)
    2.97 (2.52 to 3.51)
        Serogroup W - 6 mo Post-3rd dose (N=153,165)
    15 (12 to 18)
    2.23 (2.06 to 2.4)
        Serogroup Y - Baseline (N=108,113)
    2.43 (2.19 to 2.71)
    2.32 (2.13 to 2.52)
        Serogroup Y - 6 mo Post-3rd dose (N=153,159)
    8.39 (6.9 to 10)
    2.09 (2 to 2.19)
    No statistical analyses for this end point

    Secondary: 11. Percentage of Subjects With Four-fold Increase in hSBA Titers Against Serogroup A, C, W and Y One Month After Toddler Vaccination

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    End point title
    		 11. Percentage of Subjects With Four-fold Increase in hSBA Titers Against Serogroup A, C, W and Y One Month After Toddler Vaccination
    End point description
    The immune response was measured as the percentage of subjects who achieved four-fold increase in hSBA titers against meningococcal serogroup A, C, W and Y one month after toddler vaccination administered at 12 months of age (compared to hSBA at Month 12, just before toddler dose). Analysis was performed on the PP toddler dataset for MenACWY-CRM.
    End point type
    Secondary
    End point timeframe
    One month after toddler vaccination (month 13)
    End point values
    		 MenACWY-CRM + Routine Vaccines Routine Vaccines
    Number of subjects analysed
    168
    175
    Units: Percentage of subjects
    number (confidence interval 95%)
        Serogroup A (N=168,175)
    89 (83 to 93)
    1 (0.014 to 3)
        Serogroup C (N=156,171)
    92 (87 to 96)
    1 (0 to 4)
        Serogroup W (N=153,165)
    95 (91 to 98)
    2 (1 to 6)
        Serogroup Y (N=153,159)
    96 (92 to 99)
    1 (0.016 to 3)
    No statistical analyses for this end point

    Secondary: 12. Safety of MenACWY-CRM Vaccinations When Administered Concomitantly With Routine Vaccinations

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    End point title
    		 12. Safety of MenACWY-CRM Vaccinations When Administered Concomitantly With Routine Vaccinations
    End point description
    Safety of the study vaccines (MenACWY-CRM and other routine vaccines) was assessed in terms of the number of subjects who reported adverse events (AEs) and/or serious AEs per vaccine group at the following time points: entire study period, after infants vaccination (up to 7 months), between 2- and 4-months, between 4- and 6-months, between 6- and 12-months, between 7- and 12-months, 28 days after 12-month vaccination, and between 29 days after 12-month vaccination and study termination. Solicited reactions were not collected during this study. The safety analyses also included any AEs observed by study personnel within 15 minutes following vaccination. All AEs and SAEs were judged by the investigator as probably related, possibly related, or not related to vaccine. Analysis was done on Safety Set, i.e. all subjects in the exposed population who provide post-baseline safety data.
    End point type
    Secondary
    End point timeframe
    From visit 1 (2 months of age) through visit 7 (18 months of age)
    End point values
    		 MenACWY-CRM + Routine Vaccines Routine Vaccines
    Number of subjects analysed
    255
    270
    Units: Percentage of subjects
    number (not applicable)
        Entire study - Any AEs
    228
    239
        Entire study - At least possibly related AEs
    6
    2
        Entire study - Serious AEs
    21
    20
        Up to 7 months - Any AEs
    183
    189
        Up to 7 months - At least possibly related AEs
    6
    1
        Up to 7 months - Serious AEs
    7
    8
        Between 2- and 4-months - Any AEs
    99
    105
        Between 2- & 4-mo - At least possibly related AEs
    1
    0
        Between 2- and 4-months - Serious AEs
    5
    5
        Between 4- and 6-months - Any AEs
    118
    114
        Between 4- & 6-mo - At least possibly related AEs
    3
    0
        Between 4- and 6-months - Serious AEs
    2
    2
        Between 6- and 12-months - Any AEs
    187
    197
        Between 6- & 12-mo - At least possibly related AEs
    2
    1
        Between 6- and 12-months - Serious AEs
    10
    2
        Between 7- and 12-months - Any AEs
    175
    181
        Between 7- & 12-mo - At least possibly related AEs
    0
    0
        Between 7- and 12-months - Serious AEs
    9
    2
        28 days post-toddler - Any AEs
    80
    78
        28 days post-toddler-At least possibly related AEs
    0
    0
        28 days post-toddler - Serious AEs
    1
    1
        Between 29 days and study termination - Any AEs
    137
    137
        B/w 29 days & study terminat-Possibly related AEs
    0
    0
        Between 29 days and study termination - SeriousAEs
    7
    11
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    from day 1 to 18 months
    Adverse event reporting additional description
    The number of subjects reported here is from the safety set and not from the enrolled set.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Routine Vaccines
    Reporting group description
    		 Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

    Reporting group title
    MenACWY-CRM + Routine Vaccines
    Reporting group description
    		 Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as an infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

    Serious adverse events
    		 Routine Vaccines MenACWY-CRM + Routine Vaccines
    Total subjects affected by serious adverse events
         subjects affected / exposed
    20 / 270 (7.41%)
    21 / 255 (8.24%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Investigations
    Moraxella Test Positive
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Skull fracture
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Laryngomalacia
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Colectomy
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 255 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colostomy
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 255 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 255 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cognitive Disorder
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile Convulsion
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotonia
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sensory disturbance
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 255 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal Motility Disorder
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 255 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired Gastric Emptying
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 255 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Vaginal laceration
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory Distress
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchiolitis
         subjects affected / exposed
    2 / 270 (0.74%)
    4 / 255 (1.57%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    2 / 270 (0.74%)
    0 / 255 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 270 (0.74%)
    0 / 255 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium Difficile Infection
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 255 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Croup Infectious
         subjects affected / exposed
    3 / 270 (1.11%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis Enteroviral
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metapneumovirus Infection
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis Media
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia Parainfluenzae Viral
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 255 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 270 (0.37%)
    2 / 255 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia Viral
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 270 (0.37%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory Syncytial Virus Bronchiolitis
         subjects affected / exposed
    2 / 270 (0.74%)
    3 / 255 (1.18%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 255 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous Abscess
         subjects affected / exposed
    1 / 270 (0.37%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral Infection
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 255 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    2 / 270 (0.74%)
    0 / 255 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 255 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure To Thrive
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 255 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Routine Vaccines MenACWY-CRM + Routine Vaccines
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    227 / 270 (84.07%)
    216 / 255 (84.71%)
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    45 / 270 (16.67%)
    43 / 255 (16.86%)
         occurrences all number
    58
    51
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    24 / 270 (8.89%)
    18 / 255 (7.06%)
         occurrences all number
    24
    18
    Diarrhoea
         subjects affected / exposed
    26 / 270 (9.63%)
    25 / 255 (9.80%)
         occurrences all number
    28
    25
    Teething
         subjects affected / exposed
    7 / 270 (2.59%)
    16 / 255 (6.27%)
         occurrences all number
    7
    18
    Vomiting
         subjects affected / exposed
    31 / 270 (11.48%)
    19 / 255 (7.45%)
         occurrences all number
    33
    23
    Respiratory, thoracic and mediastinal disorders
    Bronchial hyperreactivity
         subjects affected / exposed
    8 / 270 (2.96%)
    15 / 255 (5.88%)
         occurrences all number
    9
    15
    Cough
         subjects affected / exposed
    27 / 270 (10.00%)
    34 / 255 (13.33%)
         occurrences all number
    34
    51
    Rhinitis allergic
         subjects affected / exposed
    21 / 270 (7.78%)
    17 / 255 (6.67%)
         occurrences all number
    31
    33
    Wheezing
         subjects affected / exposed
    8 / 270 (2.96%)
    16 / 255 (6.27%)
         occurrences all number
    8
    18
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    28 / 270 (10.37%)
    29 / 255 (11.37%)
         occurrences all number
    30
    29
    Dermatitis atopic
         subjects affected / exposed
    17 / 270 (6.30%)
    17 / 255 (6.67%)
         occurrences all number
    18
    18
    Dermatitis diaper
         subjects affected / exposed
    40 / 270 (14.81%)
    33 / 255 (12.94%)
         occurrences all number
    47
    46
    Rash
         subjects affected / exposed
    15 / 270 (5.56%)
    13 / 255 (5.10%)
         occurrences all number
    17
    13
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    55 / 270 (20.37%)
    60 / 255 (23.53%)
         occurrences all number
    74
    63
    Bronchitis
         subjects affected / exposed
    15 / 270 (5.56%)
    15 / 255 (5.88%)
         occurrences all number
    16
    17
    Bronchiolitis
         subjects affected / exposed
    40 / 270 (14.81%)
    37 / 255 (14.51%)
         occurrences all number
    50
    44
    Candida nappy rash
         subjects affected / exposed
    17 / 270 (6.30%)
    6 / 255 (2.35%)
         occurrences all number
    19
    6
    Candida infection
         subjects affected / exposed
    24 / 270 (8.89%)
    16 / 255 (6.27%)
         occurrences all number
    28
    21
    Croup infectious
         subjects affected / exposed
    21 / 270 (7.78%)
    15 / 255 (5.88%)
         occurrences all number
    22
    16
    Otitis media
         subjects affected / exposed
    101 / 270 (37.41%)
    100 / 255 (39.22%)
         occurrences all number
    226
    249
    Gastroenteritis
         subjects affected / exposed
    32 / 270 (11.85%)
    38 / 255 (14.90%)
         occurrences all number
    37
    44
    Otitis media acute
         subjects affected / exposed
    31 / 270 (11.48%)
    31 / 255 (12.16%)
         occurrences all number
    50
    46
    Pharyngitis
         subjects affected / exposed
    32 / 270 (11.85%)
    24 / 255 (9.41%)
         occurrences all number
    43
    27
    Rhinitis
         subjects affected / exposed
    20 / 270 (7.41%)
    19 / 255 (7.45%)
         occurrences all number
    20
    19
    Sinusitis
         subjects affected / exposed
    15 / 270 (5.56%)
    10 / 255 (3.92%)
         occurrences all number
    15
    21
    Upper respiratory tract infection
         subjects affected / exposed
    154 / 270 (57.04%)
    144 / 255 (56.47%)
         occurrences all number
    321
    300
    Viral infection
         subjects affected / exposed
    51 / 270 (18.89%)
    36 / 255 (14.12%)
         occurrences all number
    58
    49

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Nov 2009
    - The subjects in Group 2, the Control group will be administered one dose of MenACWY at Visit 7 with one month of follow up. This will extend the study period by 1 month, from 16 months to 17 months.
    21 Jan 2010
    - Need to clarify what vaccines can be administered and when they should be administered. - Need to clarify where injection should be given.
    29 Jul 2011
    - The protocol is being amended to reflect changes to the primary and secondary endpoints, and to describe the switch from Pre-Filled Syringe (PFS) to vial-vial presentation.

    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
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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