Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43845   clinical trials with a EudraCT protocol, of which   7282   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 3b, Randomized, Observer-Blind, Placebo-Controlled Multicenter Study Comparing Immunogenicity, Safety and 1 Year Persistence of Antibodies after either One or Two Doses of Novartis Meningococcal ACWY Conjugate Vaccine, administered to Healthy Children 2 to 10 years of age.

    Summary
    EudraCT number
    		 2011-004421-27
    Trial protocol
    		 HU  
    Global end of trial date
    30 May 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 May 2016
    First version publication date
    25 Apr 2015
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    V59_57
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01682876
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Vaccines and Diagnostics
    Sponsor organisation address
    350 Massachusetts Avenue, Cambridge, MA, United States, 02139
    Public contact
    Posting Director, Novartis Vaccines and Diagnostics, RegistryContactVaccinesUS@novartis.com
    Scientific contact
    Posting Director, Novartis Vaccines and Diagnostics, 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
    13 Nov 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 May 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate noninferiority of 2 doses (given 2 months apart) versus 1 dose of meningococcal groups A, C, W, and Y oligosaccharide diphtheria CRM-197 conjugate (MenACWY-CRM) vaccine, by age group (2 to 5 years of age; 6 to 10 years of age), as measured by the percentage of subjects with a serum bactericidal assay using human complement (hSBA) seroresponse directed against N meningitidis serogroups A, C, W and Y, at 1 month after last vaccination. 2. To demonstrate superiority of 2 doses (given 2 months apart) versus 1 dose of MenACWY-CRM vaccine, by age group (2 to 5 years of age; 6 to 10 years of age), as measured by the percentage of subjects with hSBA seroresponse directed against N meningitidis serogroups A, C, W and Y, at 1 month after last vaccination.
    Protection of trial subjects
    This clinical study was designed, implemented and reported in accordance with the International Conference on Harmonization (ICH) Harmonized Tripartite Guidelines for Good Clinical Practice (GCP), with applicable local regulations (including European Directive 2001/20/EC, United States (US) Code of Federal Regulations Title 21, and Japanese Ministry of Health, Labor, and Welfare), and with the ethical principles laid down in the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 Oct 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 1 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 715
    Worldwide total number of subjects
    715
    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)
    0
    Children (2-11 years)
    715
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects were enrolled at 22 locations.

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

    Period 1
    Period 1 title
    Period 1 (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    During the study, unblinded qualified health care personnel administered the study vaccine or placebo to the subjects, and were instructed not to reveal the identity of the study vaccine/placebo to the subject/subject’s parents/legal guardians or to the investigative site personnel monitoring or conducting the study, except in emergency situations. Information on study vaccine/placebo allocations was not available to the investigator or monitoring personnel until completion of the trial.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 2 Through 5 Years (2 Vac)
    Arm description
    		 Subjects 2-5 years of age received two MenACWY-CRM vaccinations.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 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
    2 doses of 0.5 mL

    Arm title
    		 2 Through 5 Years (1 Vac)
    Arm description
    		 Subjects 2-5 years of age received one MenACWY-CRM vaccination.
    Arm type
    		 Placebo 1st vac, active comparator 2nd vac

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 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
    1 dose of 0.5 mL

    Arm title
    		 6 Through 10 Years (2 Vac)
    Arm description
    		 Subjects 6-10 years of age received two MenACWY-CRM vaccinations.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 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
    2 doses of 0.5 mL

    Arm title
    		 6 Through 10 Years (1 Vac)
    Arm description
    		 Subjects 6-10 years of age received one MenACWY-CRM vaccination.
    Arm type
    		 Placebo 1st vac, active comparator 2nd vac

    Investigational medicinal product name
    Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 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
    1 dose of 0.5 mL

    Number of subjects in period 1
    		2 Through 5 Years (2 Vac) 2 Through 5 Years (1 Vac) 6 Through 10 Years (2 Vac) 6 Through 10 Years (1 Vac)
    Started
    176
    183
    180
    176
    Completed
    155
    163
    169
    157
    Not completed
    21
    20
    11
    19
         Consent withdrawn by subject
    4
    -
    -
    2
         Adverse Event
    -
    -
    -
    1
         Other
    1
    -
    1
    1
         Administrative Reason
    4
    4
    -
    3
         Lost to follow-up
    11
    15
    9
    11
         Protocol deviation
    1
    1
    1
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    2 Through 5 Years (2 Vac)
    Reporting group description
    		 Subjects 2-5 years of age received two MenACWY-CRM vaccinations.

    Reporting group title
    2 Through 5 Years (1 Vac)
    Reporting group description
    		 Subjects 2-5 years of age received one MenACWY-CRM vaccination.

    Reporting group title
    6 Through 10 Years (2 Vac)
    Reporting group description
    		 Subjects 6-10 years of age received two MenACWY-CRM vaccinations.

    Reporting group title
    6 Through 10 Years (1 Vac)
    Reporting group description
    		 Subjects 6-10 years of age received one MenACWY-CRM vaccination.

    Reporting group values
    		 2 Through 5 Years (2 Vac) 2 Through 5 Years (1 Vac) 6 Through 10 Years (2 Vac) 6 Through 10 Years (1 Vac) Total
    Number of subjects
    		 176 183 180 176 715
    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: years
        arithmetic mean (standard deviation)
    		 3.5 ± 1.1 3.6 ± 1.2 7.8 ± 1.4 7.8 ± 1.4 -
    Gender categorical
    Units: Subjects
        Female
    		 84 88 97 87 356
        Male
    		 92 95 83 89 359

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    2 Through 5 Years (2 Vac)
    Reporting group description
    		 Subjects 2-5 years of age received two MenACWY-CRM vaccinations.

    Reporting group title
    2 Through 5 Years (1 Vac)
    Reporting group description
    		 Subjects 2-5 years of age received one MenACWY-CRM vaccination.

    Reporting group title
    6 Through 10 Years (2 Vac)
    Reporting group description
    		 Subjects 6-10 years of age received two MenACWY-CRM vaccinations.

    Reporting group title
    6 Through 10 Years (1 Vac)
    Reporting group description
    		 Subjects 6-10 years of age received one MenACWY-CRM vaccination.

    Primary: Non-inferiority of Two Vaccinations Versus One Vaccination of MenACWY-CRM, by Age Cohort, as Measured by the Percentage of Subjects With hSBA Seroresponse Against N Meningitidis Serogroups A, C, W and Y, at 1 Month After Last Vaccination

    		 Close Top of page
    End point title
    		 Non-inferiority of Two Vaccinations Versus One Vaccination of MenACWY-CRM, by Age Cohort, as Measured by the Percentage of Subjects With hSBA Seroresponse Against N Meningitidis Serogroups A, C, W and Y, at 1 Month After Last Vaccination
    End point description
    Immunogenicity was measured as the percentage of subjects with overall seroresponse and associated 95% Clopper-Pearson confidence interval (CI), directed against N. meningitidis serogroups A, C, W and Y, by serum bactericidal assay using human complement (hSBA) at 1 month after one vaccination or two vaccinations of MenACWY-CRM given two months apart. Seroresponse is defined as: 1. postvaccination hSBA titer ≥1:8 for subjects with a prevaccination hSBA titer <1:4; 2. for subjects with a prevaccination hSBA ≥1:4, an increase of at least four times of the prevaccination hSBA titer.
    End point type
    Primary
    End point timeframe
    One Month After Last Vaccination (day 86)
    End point values
    		 2 Through 5 Years (2 Vac) 2 Through 5 Years (1 Vac) 6 Through 10 Years (2 Vac) 6 Through 10 Years (1 Vac)
    Number of subjects analysed
    135
    143
    152
    142
    Units: Percentage of subjects
    number (confidence interval 95%)
        MenA (N=135,143,152,142)
    94 (89 to 97)
    75 (67 to 82)
    89 (83 to 93)
    77 (70 to 84)
        MenC (N=131,140,149,142)
    92 (86 to 96)
    65 (56 to 73)
    93 (87 to 96)
    73 (65 to 80)
        MenW (N=128,135,148,138)
    75 (67 to 82)
    61 (52 to 69)
    58 (50 to 66)
    54 (45 to 62)
        MenY (N=128,133,148,142)
    91 (84 to 95)
    64 (55 to 72)
    89 (83 to 94)
    60 (51 to 68)
    Statistical analysis title
    		 Non-inferiority of 2 Vac to 1 Vac, MenA
    Statistical analysis description
    Two vaccinations versus one vaccination of MenACWY-CRM, for 2 to 5 years of age cohort, as measured by the percentage of subjects with hSBA seroresponse against N Meningitidis serogroups A at 1 month after last vaccination.
    Comparison groups
    2 Through 5 Years (2 Vac) v 2 Through 5 Years (1 Vac)
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    		 Method of Miettinen and Nurminen (MN)
    Parameter type
    		 Vaccine-group difference
    Point estimate
    19
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 10
         upper limit
    		 28.9
    Notes
    [1] - Noninferiority was demonstrated for 2 to 5 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for MenA.
    Statistical analysis title
    		 Non-inferiority of 2 Vac to 1 Vac, MenC
    Statistical analysis description
    Non-inferiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup C, at 1 month after last vaccination, for age cohort 2 – 5 years of age.
    Comparison groups
    2 Through 5 Years (2 Vac) v 2 Through 5 Years (1 Vac)
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    27
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 16.9
         upper limit
    		 37.7
    Notes
    [2] - Noninferiority was demonstrated for 2 to 5 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for MenC.
    Statistical analysis title
    		 Non-inferiority of 2 Vac to 1 Vac, MenW
    Statistical analysis description
    Non-inferiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup W, at 1 month after last vaccination, for age cohort 2 – 5 years of age.
    Comparison groups
    2 Through 5 Years (2 Vac) v 2 Through 5 Years (1 Vac)
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    14
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 1.4
         upper limit
    		 26.7
    Notes
    [3] - Noninferiority was demonstrated for 2 to 5 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for MenW.
    Statistical analysis title
    		 Non-inferiority of 2 Vac to 1 Vac, MenY
    Statistical analysis description
    Non-inferiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup Y, at 1 month after last vaccination, for age cohort 2 – 5 years of age.
    Comparison groups
    2 Through 5 Years (2 Vac) v 2 Through 5 Years (1 Vac)
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    27
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 15.6
         upper limit
    		 37.6
    Notes
    [4] - Noninferiority was demonstrated for 2 to 5 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for Men Y.
    Statistical analysis title
    		 Non-inferiority of 2 Vac to 1 Vac, MenA
    Statistical analysis description
    Non-inferiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup A, at 1 month after last vaccination, for age cohort 6 – 10 years of age.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    294
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    11
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 1.7
         upper limit
    		 21.3
    Notes
    [5] - Noninferiority was demonstrated for 6 to 10 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for MenA.
    Statistical analysis title
    		 Non-inferiority of 2 Vac to 1 Vac, MenC
    Statistical analysis description
    Non-inferiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup C, at 1 month after last vaccination, for age cohort 6 – 10 years of age.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    294
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    19
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 9.9
         upper limit
    		 29.2
    Notes
    [6] - Noninferiority was demonstrated for 6 to 10 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for MenC.
    Statistical analysis title
    		 Non-inferiority of 2 Vac to 1 Vac, MenW
    Statistical analysis description
    Non-inferiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup W, at 1 month after last vaccination, for age cohort 6 – 10 years of age.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    294
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [7]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    4
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -8.6
         upper limit
    		 17.4
    Notes
    [7] - Noninferiority was demonstrated for 6 to 10 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for MenW.
    Statistical analysis title
    		 Non-inferiority of 2 Vac to 1 Vac, MenY
    Statistical analysis description
    Non-inferiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup Y, at 1 month after last vaccination, for age cohort 6 – 10 years of age.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    294
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    29
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 18.4
         upper limit
    		 40
    Notes
    [8] - Noninferiority was demonstrated for 6 to 10 years of age group if the lower limit of the 2-sided 97.5% confidence interval (CI) for the difference in seroresponse rate between the 2-dose vaccination schedule and the 1-dose vaccination schedule (2-dose schedule minus the 1-dose schedule) was greater than -10% for MenY.

    Primary: Superiority of Two Vaccinations Versus One Vaccination of MenACWY-CRM, by Age Cohort, as Measured by the Percentage of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroups A, C, W and Y, at 1 Month After Last Vaccination

    		 Close Top of page
    End point title
    		 Superiority of Two Vaccinations Versus One Vaccination of MenACWY-CRM, by Age Cohort, as Measured by the Percentage of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroups A, C, W and Y, at 1 Month After Last Vaccination
    End point description
    Immunogenicity was measured as the percentage of subjects with overall seroresponse and associated 95% CI, directed against N. meningitidis serogroups A, C, W and Y, by hSBA at 1 month after one vaccination or two vaccinations of MenACWY-CRM. Seroresponse -postvaccination hSBA titer ≥1:8 for subjects with a prevaccination hSBA titer <1:4 and for subjects with a prevaccination hSBA ≥1:4, an increase of at least four times of the prevaccination hSBA titer.
    End point type
    Primary
    End point timeframe
    1 Month After Last Vaccination (day 86)
    End point values
    		 2 Through 5 Years (2 Vac) 2 Through 5 Years (1 Vac) 6 Through 10 Years (2 Vac) 6 Through 10 Years (1 Vac)
    Number of subjects analysed
    158
    163
    171
    163
    Units: Percentage of subjects
    number (confidence interval 95%)
        MenA (N=158,163,171,163)
    95 (90 to 98)
    77 (69 to 83)
    89 (84 to 94)
    79 (71 to 85)
        MenC (N=154,157,167,162)
    93 (88 to 96)
    65 (57 to 72)
    93 (89 to 97)
    75 (68 to 82)
        MenW (N=150,154,167,159)
    75 (68 to 82)
    61 (53 to 69)
    57 (49 to 65)
    52 (44 to 60)
        MenY (N=150,153,167,163)
    90 (84 to 94)
    62 (54 to 70)
    89 (83 to 93)
    60 (52 to 68)
    Statistical analysis title
    		 Superiority of 2 Vac to 1 Vac, MenA
    Statistical analysis description
    Superiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup A, at 1 month after last vaccination, for age cohort 2 – 5 years of age.
    Comparison groups
    2 Through 5 Years (2 Vac) v 2 Through 5 Years (1 Vac)
    Number of subjects included in analysis
    321
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    18
    Confidence interval
         level
    		 98.75%
         sides
    2-sided
         lower limit
    		 9.1
         upper limit
    		 28
    Notes
    [9] - Superiority was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenA.
    Statistical analysis title
    		 Superiority of 2 Vac to 1 Vac, MenC
    Statistical analysis description
    Superiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup C, at 1 month after last vaccination, for age cohort 2 – 5 years of age.
    Comparison groups
    2 Through 5 Years (1 Vac) v 2 Through 5 Years (2 Vac)
    Number of subjects included in analysis
    321
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    28
    Confidence interval
         level
    		 98.75%
         sides
    2-sided
         lower limit
    		 17.1
         upper limit
    		 38.7
    Notes
    [10] - Superiority was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenC.
    Statistical analysis title
    		 Superiority of 2 Vac to 1 Vac, MenW
    Statistical analysis description
    Superiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup W, at 1 month after last vaccination, for age cohort 2 – 5 years of age.
    Comparison groups
    2 Through 5 Years (2 Vac) v 2 Through 5 Years (1 Vac)
    Number of subjects included in analysis
    321
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    14
    Confidence interval
         level
    		 98.75%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 27.1
    Notes
    [11] - Superiority was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenW.
    Statistical analysis title
    		 Superiority of 2 Vac to 1 Vac, MenY
    Statistical analysis description
    Superiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup Y, at 1 month after last vaccination, for age cohort 2 – 5 years of age.
    Comparison groups
    2 Through 5 Years (2 Vac) v 2 Through 5 Years (1 Vac)
    Number of subjects included in analysis
    321
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [12]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    28
    Confidence interval
         level
    		 98.75%
         sides
    2-sided
         lower limit
    		 16.2
         upper limit
    		 39.3
    Notes
    [12] - Superiority was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenY.
    Statistical analysis title
    		 Superiority of 2 Vac to 1 Vac, MenA
    Statistical analysis description
    Superiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup A, at 1 month after last vaccination, for age cohort 6 – 10 years of age.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    11
    Confidence interval
         level
    		 98.75%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 21.2
    Notes
    [13] - Superiority was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenA.
    Statistical analysis title
    		 Superiority of 2 Vac to 1 Vac, MenC
    Statistical analysis description
    Superiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup C, at 1 month after last vaccination, for age cohort 6 – 10 years of age.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [14]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    18
    Confidence interval
         level
    		 98.75%
         sides
    2-sided
         lower limit
    		 8.5
         upper limit
    		 28.2
    Notes
    [14] - Superiority was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenC.
    Statistical analysis title
    		 Superiority of 2 Vac to 1 Vac, MenW
    Statistical analysis description
    Superiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup W, at 1 month after last vaccination, for age cohort 6 – 10 years of age.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [15]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    5
    Confidence interval
         level
    		 98.75%
         sides
    2-sided
         lower limit
    		 -8.4
         upper limit
    		 18.8
    Notes
    [15] - Superiority was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenW.
    Statistical analysis title
    		 Superiority of 2 Vac to 1 Vac, MenY
    Statistical analysis description
    Superiority of two vaccinations versus one vaccination of MenACWY-CRM, as measured by the percentage of subjects with hSBA seroresponse against N. Meningitidis serogroup Y, at 1 month after last vaccination, for age cohort 6 – 10 years of age.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [16]
    Method
    		 MN Method
    Parameter type
    		 Vaccine-group difference
    Point estimate
    29
    Confidence interval
         level
    		 98.75%
         sides
    2-sided
         lower limit
    		 17
         upper limit
    		 39.6
    Notes
    [16] - Superiority was demonstrated if the lower limit of the 2-sided (1-2α) % CI for seroresponse increase between the 2-dose vaccination schedule and the 1-dose vaccination schedule was above 10% for MenY.

    Secondary: Percentage of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Month After One or Two Vaccination(s) of MenACWY-CRM

    		 Close Top of page
    End point title
    		 Percentage of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Month After One or Two Vaccination(s) of MenACWY-CRM
    End point description
    Immunogenicity was measured as the percentage of subjects who achieved hSBA titer ≥1:8 and associated 95% CI, at one month after one vaccination or two vaccinations of MenACWY-CRM.
    End point type
    Secondary
    End point timeframe
    One Month After Last Vaccination ( day 86)
    End point values
    		 2 Through 5 Years (2 Vac) 2 Through 5 Years (1 Vac) 6 Through 10 Years (2 Vac) 6 Through 10 Years (1 Vac)
    Number of subjects analysed
    135
    143
    152
    142
    Units: Percentage of subjects
    number (confidence interval 95%)
        MenA (N=135,143,152,142)
    95 (90 to 98)
    76 (68 to 82)
    91 (85 to 95)
    80 (73 to 86)
        MenC (N=131,140,149,142)
    98 (95 to 100)
    76 (68 to 83)
    99 (95 to 100)
    89 (82 to 93)
        MenW (N=128,135,148,138)
    99 (96 to 100)
    92 (86 to 96)
    99 (96 to 100)
    96 (91 to 98)
        MenY (N=128,133,148,142)
    96 (91 to 99)
    69 (61 to 77)
    96 (91 to 98)
    73 (64 to 80)
    No statistical analyses for this end point

    Secondary: Geometric Mean Titers of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Month After One or Two Vaccination(s) of MenACWY-CRM

    		 Close Top of page
    End point title
    		 Geometric Mean Titers of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Month After One or Two Vaccination(s) of MenACWY-CRM
    End point description
    Immunogenicity was measured as hSBA geometric mean titers (GMTs) and 95% CI against N. meningitidis serogroups A, C, W and Y, one month after one vaccination or two vaccinations of MenACWY-CRM.
    End point type
    Secondary
    End point timeframe
    One Month After Last Vaccination ( day 86)
    End point values
    		 2 Through 5 Years (2 Vac) 2 Through 5 Years (1 Vac) 6 Through 10 Years (2 Vac) 6 Through 10 Years (1 Vac)
    Number of subjects analysed
    135
    143
    152
    142
    Units: Titer
    geometric mean (confidence interval 95%)
        MenA (N=135,143,152,142)
    68 (54 to 86)
    21 (17 to 27)
    67 (52 to 87)
    36 (28 to 47)
        MenC (N=131,140,149,142)
    146 (115 to 186)
    22 (18 to 28)
    165 (126 to 217)
    67 (51 to 89)
        MenW (N=128,135,148,138)
    191 (150 to 243)
    104 (83 to 132)
    169 (138 to 206)
    95 (78 to 117)
        MenY (N=128,133,148,142)
    70 (55 to 90)
    15 (12 to 19)
    76 (58 to 99)
    26 (20 to 34)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Year After One or Two Vaccination(s) of MenACWY-CRM

    		 Close Top of page
    End point title
    		 Percentage of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Year After One or Two Vaccination(s) of MenACWY-CRM
    End point description
    Immunogenicity was measured as the percentage of subjects with hSBA titer ≥1:8 and associated 95% CI at one year after one vaccination or two vaccinations of MenACWY-CRM.
    End point type
    Secondary
    End point timeframe
    One year after one vaccination or two vaccinations (day 422).
    End point values
    		 2 Through 5 Years (2 Vac) 2 Through 5 Years (1 Vac) 6 Through 10 Years (2 Vac) 6 Through 10 Years (1 Vac)
    Number of subjects analysed
    123
    131
    142
    130
    Units: Percentage of subjects
    number (confidence interval 95%)
        MenA (N=122,131,142,130)
    30 (22 to 39)
    11 (6 to 17)
    30 (22 to 38)
    20 (14 to 28)
        MenC (N=123,128,141,130)
    61 (52 to 70)
    41 (32 to 50)
    81 (73 to 87)
    55 (46 to 64)
        MenW (N=121,127,139,130)
    92 (85 to 96)
    91 (84 to 95)
    94 (89 to 97)
    90 (84 to 95)
        MenY (N=121,122,140,130)
    67 (58 to 75)
    57 (48 to 66)
    75 (67 to 82)
    65 (57 to 74)
    No statistical analyses for this end point

    Secondary: Geometric Mean Titers of Subjects, Directed Against N Meningitidis Serogroups A, C, W and Y At One Year After One or Two Vaccination(s) of MenACWY-CRM

    		 Close Top of page
    End point title
    		 Geometric Mean Titers of Subjects, Directed Against N Meningitidis Serogroups A, C, W and Y At One Year After One or Two Vaccination(s) of MenACWY-CRM
    End point description
    Immunogenicity was measured as hSBA GMTs and 95% CI against N. meningitidis serogroups A, C, W and Y at one year after one vaccination or two vaccinations of MenACWY-CRM.
    End point type
    Secondary
    End point timeframe
    One year after one vaccination or two vaccinations (day 422).
    End point values
    		 2 Through 5 Years (2 Vac) 2 Through 5 Years (1 Vac) 6 Through 10 Years (2 Vac) 6 Through 10 Years (1 Vac)
    Number of subjects analysed
    123
    131
    142
    130
    Units: Titer
    geometric mean (confidence interval 95%)
        MenA (N=122,131,142,130)
    4.72 (3.91 to 5.71)
    2.66 (2.22 to 3.19)
    4.66 (3.75 to 5.81)
    3.56 (2.84 to 4.46)
        MenC (N=123,128,141,130)
    10 (8.34 to 13)
    7.03 (5.63 to 8.76)
    24 (18 to 31)
    15 (12 to 20)
        MenW (N=121,127,139,130)
    49 (39 to 62)
    39 (31 to 49)
    64 (52 to 79)
    47 (38 to 59)
        MenY (N=121,122,140,130)
    14 (11 to 17)
    9.88 (7.8 to 13)
    20 (15 to 25)
    13 (9.96 to 16)
    No statistical analyses for this end point

    Secondary: Numbers of 2 to 5 Years-Old Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination

    		 Close Top of page
    End point title
    		 Numbers of 2 to 5 Years-Old Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination [17]
    End point description
    Safety was assessed as the number of 2 to 5 years-old subjects who reported solicited local and systemic adverse events (AEs) from day 1 up to and including day 7 after one or two vaccination(s) of MenACWY-CRM.
    End point type
    Secondary
    End point timeframe
    From day 1 through day 7 after one or two vaccination(s)
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint specifically only investigates subjects 2 trough 5 years old, which means the reporting groups 6 Through 10 years (1 vac) and 6 Through 10 years (2 Vac) are out of scope.
    End point values
    		 2 Through 5 Years (2 Vac) 2 Through 5 Years (1 Vac)
    Number of subjects analysed
    174
    175
    Units: Number of subjects
        Erythema (N=173,175)
    25
    11
        Induration (N=173,175)
    19
    7
        Tenderness (N=174,175)
    84
    79
        Change in eating habits (N=173,175)
    26
    30
        Sleepiness (N=173,175)
    49
    46
        Irritability (N=173,175)
    51
    50
        Body Temperature ≥38°C (N=174,175)
    9
    12
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, erythema
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced erythema in the two doses versus in the one dose of MenACWY.
    Comparison groups
    2 Through 5 Years (2 Vac) v 2 Through 5 Years (1 Vac)
    Number of subjects included in analysis
    349
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.17
         upper limit
    		 4.53
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, induration
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced induration in the two doses versus in the one dose of MenACWY.
    Comparison groups
    2 Through 5 Years (2 Vac) v 2 Through 5 Years (1 Vac)
    Number of subjects included in analysis
    349
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    2.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.18
         upper limit
    		 6.36
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, tenderness
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced tenderness in the two doses versus in the one dose of MenACWY.
    Comparison groups
    2 Through 5 Years (2 Vac) v 2 Through 5 Years (1 Vac)
    Number of subjects included in analysis
    349
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.34
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, chng. eating habits
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced a change in eating habits in the two doses versus in the one dose of MenACWY.
    Comparison groups
    2 Through 5 Years (2 Vac) v 2 Through 5 Years (1 Vac)
    Number of subjects included in analysis
    349
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.42
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, sleepiness
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced sleepiness in the two doses versus in the one dose of MenACWY.
    Comparison groups
    2 Through 5 Years (2 Vac) v 2 Through 5 Years (1 Vac)
    Number of subjects included in analysis
    349
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.52
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, irritability
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced irritability in the two doses versus in the one dose of MenACWY.
    Comparison groups
    2 Through 5 Years (2 Vac) v 2 Through 5 Years (1 Vac)
    Number of subjects included in analysis
    349
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.43
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, fever (≥38 °C)
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced fever (≥38 °C) in the two doses versus in the one dose of MenACWY.
    Comparison groups
    2 Through 5 Years (2 Vac) v 2 Through 5 Years (1 Vac)
    Number of subjects included in analysis
    349
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.33
         upper limit
    		 1.74

    Secondary: Numbers of 6 to 10 Years-Old Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination

    		 Close Top of page
    End point title
    		 Numbers of 6 to 10 Years-Old Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination [18]
    End point description
    Safety was assessed as the number of 6 to 10 years-old subjects who reported solicited local and systemic adverse events from day 1 up to and including day 7 after one or two vaccination(s) of MenACWY-CRM.
    End point type
    Secondary
    End point timeframe
    From day 1 through day 7 after one or two vaccination(s)
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint specifically only investigates subjects 6 through 10 years old, which means the reporting groups 2 Through 5 years (1 vac) and 2 Through 5 years (2 Vac) are out of scope.
    End point values
    		 6 Through 10 Years (2 Vac) 6 Through 10 Years (1 Vac)
    Number of subjects analysed
    178
    166
    Units: Number of subjects
        Erythema (N=178,166)
    23
    15
        Induration (N=178,166)
    24
    15
        Pain (N=178,166)
    106
    78
        Loss of Appetite (N=177,166)
    27
    14
        Nausea (N=177,165)
    29
    21
        Fatigue (N=177,166)
    44
    25
        Myalgia (N=177,165)
    63
    43
        Arthralgia (N=177,165)
    20
    9
        Headache (N=177,165)
    55
    28
        Body Temperature ≥38°C (N=178,166)
    11
    9
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, erythema
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced erythema in the two doses versus in the one dose of MenACWY.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    344
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 2.65
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, induration
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced induration in the two doses versus in the one dose of MenACWY.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    344
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 2.74
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, pain
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced pain in the two doses versus in the one dose of MenACWY.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    344
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.04
         upper limit
    		 1.55
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, loss of appetite
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced a loss of appetite in the two doses versus in the one dose of MenACWY.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    344
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 3.33
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, nausea
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced nausea in the two doses versus in the one dose of MenACWY.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    344
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 2.17
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, fatigue
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced fatigue in the two doses versus in the one dose of MenACWY.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    344
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.06
         upper limit
    		 2.57
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, myalgia
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced myalgia in the two doses versus in the one dose of MenACWY.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    344
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 1.89
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, arthralgia
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced arthralgia in the two doses versus in the one dose of MenACWY.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    344
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    2.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.97
         upper limit
    		 4.42
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, headache
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced headache in the two doses versus in the one dose of MenACWY.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    344
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.22
         upper limit
    		 2.74
    Statistical analysis title
    		 2 Vac vs. 1 Vac, Systemic AEs, fever (≥38 °C)
    Statistical analysis description
    The safety of two vaccine groups was compared by calculating risk ratio of the proportions of subjects who experienced fever (≥38 °C) in the two doses versus in the one dose of MenACWY.
    Comparison groups
    6 Through 10 Years (2 Vac) v 6 Through 10 Years (1 Vac)
    Number of subjects included in analysis
    344
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 2.68

    Secondary: Number of Subjects Who Reported Selected AEs After Any Vaccination – Day 1 to 86

    		 Close Top of page
    End point title
    		 Number of Subjects Who Reported Selected AEs After Any Vaccination – Day 1 to 86
    End point description
    Safety was assessed as the number subjects who reported Selected AEs from day 1 up to day 86 after one or two vaccination(s) of MenACWY.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 86
    End point values
    		 2 Through 5 Years (2 Vac) 2 Through 5 Years (1 Vac) 6 Through 10 Years (2 Vac) 6 Through 10 Years (1 Vac)
    Number of subjects analysed
    176 [19]
    179
    180 [20]
    174
    Units: Number of subjects
        SAEs
    1
    0
    0
    0
        At least possibly related SAEs
    0
    0
    0
    0
        Medically attended AEs
    50
    55
    46
    46
        At least possibly related medically attended AEs
    0
    3
    1
    0
        AEs resulting in premature withdrawal
    0
    0
    0
    1
        Deaths
    0
    0
    0
    0
    Notes
    [19] - Actual number subjects analysed in this group was 179.
    [20] - Actual number subjects analysed in this group was 181.
    No statistical analyses for this end point

    Secondary: Number of Subjects Who Reported Selected AEs After Any Vaccination – Day 1 to 422

    		 Close Top of page
    End point title
    		 Number of Subjects Who Reported Selected AEs After Any Vaccination – Day 1 to 422
    End point description
    Safety was assessed as the number subjects who reported Selected AEs from day 1 up to day 422 after one or two vaccination(s) of MenACWY.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 422
    End point values
    		 2 Through 5 Years (2 Vac) 2 Through 5 Years (1 Vac) 6 Through 10 Years (2 Vac) 6 Through 10 Years (1 Vac)
    Number of subjects analysed
    176 [21]
    179
    180 [22]
    174
    Units: Number of subjects
        SAEs
    2
    1
    1
    1
        At least possibly related SAEs
    0
    1
    0
    0
        Medically attended AEs
    103
    101
    95
    97
        At least possibly related medically attended AEs
    1
    4
    1
    2
        AEs resulting in premature withdrawal
    0
    0
    0
    1
        Deaths
    0
    0
    0
    0
    Notes
    [21] - Actual number subjects analysed in this group was 179.
    [22] - Actual number subjects analysed in this group was 181.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Solicited AEs were collected day 1-day 7, unsolicited AEs were collected day 1-day 28, after each vaccination. Medically attended AEs, AEs resulting in premature withdrawal and SAEs were collected day 1-study termination.
    Adverse event reporting additional description
    Solicited AEs were collected by systematic assessment; unsolicited AEs were collected by non-systematic assessment. MedDRA version 16.1 was used for solicited and unsolicited AEs, MedDRA version 17.0 was used for selected adverse events (see outcome measure 9), and MedDRA version 17.1 was used for additional analysis of occurence rates.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    2 Through 5 Years (2 Vac)
    Reporting group description
    		 Subjects 2-5 years of age received two MenACWY-CRM vaccinations.

    Reporting group title
    2 Through 5 Years (1 Vac)
    Reporting group description
    		 Subjects 2-5 years of age received one MenACWY-CRM vaccination.

    Reporting group title
    6 Through 10 Years (2 Vac)
    Reporting group description
    		 Subjects 6-10 years of age received two MenACWY-CRM vaccinations.

    Reporting group title
    6 Through 10 Years (1 Vac)
    Reporting group description
    		 Subjects 6-10 years of age received one MenACWY-CRM vaccination.

    Serious adverse events
    		 2 Through 5 Years (2 Vac) 2 Through 5 Years (1 Vac) 6 Through 10 Years (2 Vac) 6 Through 10 Years (1 Vac)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 179 (1.12%)
    1 / 179 (0.56%)
    1 / 181 (0.55%)
    1 / 174 (0.57%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Nervous system disorders
    Petit mal epilepsy
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 179 (0.00%)
    0 / 181 (0.00%)
    0 / 174 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Immune thrombocytopenic purpura
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    0 / 174 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    0 / 174 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis allergic
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 179 (0.00%)
    0 / 181 (0.00%)
    0 / 174 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Intermittent explosive disorder
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 179 (0.00%)
    0 / 181 (0.00%)
    1 / 174 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oppositional defiant disorder
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 179 (0.00%)
    0 / 181 (0.00%)
    1 / 174 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Otitis media
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 179 (0.00%)
    0 / 181 (0.00%)
    0 / 174 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 179 (0.00%)
    0 / 181 (0.00%)
    0 / 174 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 2 Through 5 Years (2 Vac) 2 Through 5 Years (1 Vac) 6 Through 10 Years (2 Vac) 6 Through 10 Years (1 Vac)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    136 / 179 (75.98%)
    134 / 179 (74.86%)
    142 / 181 (78.45%)
    126 / 174 (72.41%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    6 / 179 (3.35%)
    8 / 179 (4.47%)
    61 / 181 (33.70%)
    35 / 174 (20.11%)
         occurrences all number
    9
    8
    96
    50
    Somnolence
         subjects affected / exposed
    49 / 179 (27.37%)
    47 / 179 (26.26%)
    0 / 181 (0.00%)
    1 / 174 (0.57%)
         occurrences all number
    69
    60
    0
    1
    General disorders and administration site conditions
    Vomiting
         subjects affected / exposed
    19 / 179 (10.61%)
    19 / 179 (10.61%)
    15 / 181 (8.29%)
    11 / 174 (6.32%)
         occurrences all number
    23
    23
    15
    11
    Fatigue
         subjects affected / exposed
    1 / 179 (0.56%)
    1 / 179 (0.56%)
    44 / 181 (24.31%)
    25 / 174 (14.37%)
         occurrences all number
    1
    1
    64
    32
    Injection site erythema
    alternative assessment type: Systematic
         subjects affected / exposed
    25 / 179 (13.97%)
    11 / 179 (6.15%)
    24 / 181 (13.26%)
    16 / 174 (9.20%)
         occurrences all number
    31
    12
    27
    17
    Injection site induration
    alternative assessment type: Systematic
         subjects affected / exposed
    19 / 179 (10.61%)
    7 / 179 (3.91%)
    24 / 181 (13.26%)
    16 / 174 (9.20%)
         occurrences all number
    24
    8
    27
    16
    Injection site pain
    alternative assessment type: Systematic
         subjects affected / exposed
    84 / 179 (46.93%)
    79 / 179 (44.13%)
    106 / 181 (58.56%)
    78 / 174 (44.83%)
         occurrences all number
    116
    109
    152
    109
    Pyrexia
         subjects affected / exposed
    29 / 179 (16.20%)
    34 / 179 (18.99%)
    26 / 181 (14.36%)
    26 / 174 (14.94%)
         occurrences all number
    38
    45
    28
    35
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    4 / 179 (2.23%)
    6 / 179 (3.35%)
    5 / 181 (2.76%)
    9 / 174 (5.17%)
         occurrences all number
    7
    6
    8
    10
    Diarrhoea
         subjects affected / exposed
    8 / 179 (4.47%)
    10 / 179 (5.59%)
    5 / 181 (2.76%)
    5 / 174 (2.87%)
         occurrences all number
    10
    12
    5
    5
    Nausea
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 179 (0.00%)
    29 / 181 (16.02%)
    22 / 174 (12.64%)
         occurrences all number
    0
    0
    41
    25
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    22 / 179 (12.29%)
    17 / 179 (9.50%)
    12 / 181 (6.63%)
    15 / 174 (8.62%)
         occurrences all number
    29
    21
    13
    17
    Rhinitis allergic
         subjects affected / exposed
    2 / 179 (1.12%)
    10 / 179 (5.59%)
    3 / 181 (1.66%)
    1 / 174 (0.57%)
         occurrences all number
    2
    10
    3
    1
    Rhinorrhoea
         subjects affected / exposed
    14 / 179 (7.82%)
    9 / 179 (5.03%)
    3 / 181 (1.66%)
    5 / 174 (2.87%)
         occurrences all number
    18
    10
    3
    6
    Psychiatric disorders
    Eating disorder
         subjects affected / exposed
    26 / 179 (14.53%)
    30 / 179 (16.76%)
    0 / 181 (0.00%)
    0 / 174 (0.00%)
         occurrences all number
    35
    35
    0
    0
    Irritability
         subjects affected / exposed
    51 / 179 (28.49%)
    50 / 179 (27.93%)
    1 / 181 (0.55%)
    1 / 174 (0.57%)
         occurrences all number
    78
    78
    1
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 179 (0.00%)
    21 / 181 (11.60%)
    12 / 174 (6.90%)
         occurrences all number
    0
    0
    28
    12
    Myalgia
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 179 (0.00%)
    64 / 181 (35.36%)
    43 / 174 (24.71%)
         occurrences all number
    0
    0
    86
    54
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    7 / 179 (3.91%)
    11 / 179 (6.15%)
    1 / 181 (0.55%)
    3 / 174 (1.72%)
         occurrences all number
    8
    13
    1
    3
    Ear infection
         subjects affected / exposed
    15 / 179 (8.38%)
    6 / 179 (3.35%)
    5 / 181 (2.76%)
    3 / 174 (1.72%)
         occurrences all number
    18
    8
    5
    4
    Nasopharyngitis
         subjects affected / exposed
    2 / 179 (1.12%)
    11 / 179 (6.15%)
    4 / 181 (2.21%)
    4 / 174 (2.30%)
         occurrences all number
    2
    12
    4
    5
    Otitis media
         subjects affected / exposed
    19 / 179 (10.61%)
    24 / 179 (13.41%)
    7 / 181 (3.87%)
    8 / 174 (4.60%)
         occurrences all number
    26
    34
    8
    9
    Pharyngitis
         subjects affected / exposed
    16 / 179 (8.94%)
    16 / 179 (8.94%)
    18 / 181 (9.94%)
    6 / 174 (3.45%)
         occurrences all number
    18
    18
    20
    7
    Pharyngitis streptococcal
         subjects affected / exposed
    12 / 179 (6.70%)
    18 / 179 (10.06%)
    17 / 181 (9.39%)
    14 / 174 (8.05%)
         occurrences all number
    16
    22
    20
    19
    Sinusitis
         subjects affected / exposed
    8 / 179 (4.47%)
    12 / 179 (6.70%)
    6 / 181 (3.31%)
    8 / 174 (4.60%)
         occurrences all number
    10
    18
    6
    8
    Upper respiratory tract infection
         subjects affected / exposed
    22 / 179 (12.29%)
    21 / 179 (11.73%)
    13 / 181 (7.18%)
    16 / 174 (9.20%)
         occurrences all number
    24
    31
    14
    18
    Viral infection
         subjects affected / exposed
    9 / 179 (5.03%)
    13 / 179 (7.26%)
    7 / 181 (3.87%)
    4 / 174 (2.30%)
         occurrences all number
    15
    15
    8
    5
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 179 (0.56%)
    1 / 179 (0.56%)
    27 / 181 (14.92%)
    14 / 174 (8.05%)
         occurrences all number
    1
    1
    33
    19

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Apr 2012
    The study design was revised and the study became a two-stage study. The procedures for safety follow-up have been changed, as well as the safety and immunological statistical evaluation procedures.
    03 Oct 2012
    Main changes: a safety phone call was introduced at 180 days after Visit 2; an inclusion criterion was changed; the delegation of duties was changed; the text of the primary endpoint, secondary endpoints, and analysis of safety (endpoints) and tolerability was edited to align with the statistical analysis plan and the clinical study report shell; a section on data collection and source documents was added; and the laboratory procedures were updated.
    07 Jun 2013
    Main changes: the text on the success criteria, statistical hypotheses and sequential testing, sample size calculations was revised.

    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
    For support, Contact us.
    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.

    European Medicines Agency © 1995-Fri Apr 19 05:55:06 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA