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    Clinical Trial Results:
    A Phase 3b, Open Label, Controlled, Multi-Center, Extension Study to Assess the Persistence of Bactericidal Activity at 4 to 7.5 Years After Two Dose Primary Series of GlaxoSmithKline Biologicals Meningococcal B Recombinant Vaccine and the Response to a Third Dose in Adolescents and Young Adult Subjects who Previously Participated in Parent Studies V72_41 and V72P10, Compared to Naïve Healthy Controls

    Summary
    EudraCT number
    		 2017-000093-11
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    23 Sep 2016

    Results information
    Results version number
    		 v1
    This version publication date
    14 Oct 2017
    First version publication date
    14 Oct 2017
    Other versions
    		 v2 , v3 , v4

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    205218
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02446743
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline Biologicals
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.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
    22 Jun 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    22 Sep 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Sep 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    •To assess and compare the safety and tolerability of a single dose (booster) of rMenB+OMV NZ administered to follow-on subjects approximately 4 to 7.5 years after a 2 dose primary series, with that of two doses of rMenB+OMV NZ administered to naïve subjects according to a 0, 1-month schedule. •To assess serum bactericidal activity at approximately 4 to 7.5 years following a 2 dose primary series (persistence) compared to serum bactericidal activity at baseline in vaccination-naïve subjects.
    Protection of trial subjects
    The subjects were observed closely for at least 30 minutes following the administration of vaccine(s), with appropriate medical treatment readily available in case of a rare anaphylactic reaction.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 Nov 2015
    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: 63
    Country: Number of subjects enrolled
    Canada: 187
    Country: Number of subjects enrolled
    Chile: 281
    Worldwide total number of subjects
    531
    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)
    0
    Adolescents (12-17 years)
    122
    Adults (18-64 years)
    409
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Subjects were recruited from 4 sites in Australia, 6 sites in Canada and 2 sites in Chile.

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

    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 study was an open-label study. Therefore, no blinding procedures were utilized.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group 3B
    Arm description
    		 Subjects who received a third dose booster of rMenB+OMV NZ at 4 to 7.5 years after the last dose received during studies V72P10 (NCT00661713) or V72_41(NCT0142384), and had blood collected at baseline and at 3, 7 and 30 days after the third dose booster.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GlaxoSmithKline Meningococcal group B multicomponent recombinant adsorbed vaccine
    Investigational medicinal product code
    Other name
    rMenB+OMV NZ
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One dose (0.5 mL) vaccine administered by intramuscular (IM) injection in the deltoid area of the non-dominant arm.

    Arm title
    		 Group B_0_1
    Arm description
    		 Subjects who received two doses of rMenB+OMV NZ at a 0 and 1 month schedule and had blood collected at baseline, 30 days after the first dose and 3 or 7, and 30 days after the second dose.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    GlaxoSmithKline Meningococcal group B multicomponent recombinant adsorbed vaccine
    Investigational medicinal product code
    Other name
    rMenB+OMV NZ
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One dose (0.5 mL) vaccine administered by intramuscular (IM) injection in the deltoid area of the non-dominant arm.

    Number of subjects in period 1
    		Group 3B Group B_0_1
    Started
    276
    255
    Completed
    271
    250
    Not completed
    5
    5
         Consent withdrawn by subject
    1
    1
         Adverse event, non-fatal
    1
    1
         Unspecified
    2
    3
         Lost to follow-up
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Group 3B
    Reporting group description
    		 Subjects who received a third dose booster of rMenB+OMV NZ at 4 to 7.5 years after the last dose received during studies V72P10 (NCT00661713) or V72_41(NCT0142384), and had blood collected at baseline and at 3, 7 and 30 days after the third dose booster.

    Reporting group title
    Group B_0_1
    Reporting group description
    		 Subjects who received two doses of rMenB+OMV NZ at a 0 and 1 month schedule and had blood collected at baseline, 30 days after the first dose and 3 or 7, and 30 days after the second dose.

    Reporting group values
    		 Group 3B Group B_0_1 Total
    Number of subjects
    		 276 255 531
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 65 57 122
        Adults (18-64 years)
    		 211 198 409
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 19.5 ( 2.42 ) 20 ( 2.69 ) -
    Gender categorical
    Units: Subjects
        Female
    		 133 128 261
        Male
    		 143 127 270
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 11 1 12
        Asian
    		 22 18 40
        Black or African American
    		 3 2 5
        Native Hawaiian or other Pacific Islander
    		 3 8 11
        White
    		 98 74 172
        Other
    		 139 152 291

    End points

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    End points reporting groups
    Reporting group title
    Group 3B
    Reporting group description
    		 Subjects who received a third dose booster of rMenB+OMV NZ at 4 to 7.5 years after the last dose received during studies V72P10 (NCT00661713) or V72_41(NCT0142384), and had blood collected at baseline and at 3, 7 and 30 days after the third dose booster.

    Reporting group title
    Group B_0_1
    Reporting group description
    		 Subjects who received two doses of rMenB+OMV NZ at a 0 and 1 month schedule and had blood collected at baseline, 30 days after the first dose and 3 or 7, and 30 days after the second dose.

    Primary: Percentage of subjects with human serum bactericidal activity (hSBA) ≥ 1:5

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    End point title
    		 Percentage of subjects with human serum bactericidal activity (hSBA) ≥ 1:5
    End point description
    Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713.
    End point type
    Primary
    End point timeframe
    At baseline (Day 1)
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    275
    255
    Units: Percentage of subjects
    number (confidence interval 95%)
        H44/76 (N=275;255)
    33 (27.9 to 39.4)
    9 (5.5 to 12.8)
        5/99 (N=254;239)
    84 (78.7 to 88.2)
    15 (10.4 to 19.8)
        NZ98/254 (N=273;253)
    18 (13.3 to 22.6)
    8 (5.2 to 12.4)
        M10713 (N=274;255)
    74 (68.9 to 79.5)
    70 (64.2 to 75.7)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis group B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18.2
         upper limit
    		 31.4
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 62.3
         upper limit
    		 75
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.6
         upper limit
    		 15.1
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 11.9

    Primary: Percentage of subjects with hSBA ≥ 1:8

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    End point title
    		 Percentage of subjects with hSBA ≥ 1:8
    End point description
    Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713.
    End point type
    Primary
    End point timeframe
    At baseline (Day 1)
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    275
    255
    Units: Percentage of subjects
    number (confidence interval 95%)
        H44/76 (N=275;255)
    28 (23.1 to 34.1)
    6 (3.3 to 9.5)
        5/99 (N=254;239)
    81 (75.3 to 85.4)
    13 (9 to 17.9)
        NZ98/254 (N=273;253)
    14 (10.4 to 19)
    6 (3.1 to 9.1)
        M10713 (N=274;255)
    68 (62 to 73.4)
    63 (56.9 to 69.1)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 16.5
         upper limit
    		 28.6
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 60.8
         upper limit
    		 73.7
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.7
         upper limit
    		 14
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 12.8

    Primary: Percentage of subjects with hSBA ≥ 1:16

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    End point title
    		 Percentage of subjects with hSBA ≥ 1:16
    End point description
    Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713.
    End point type
    Primary
    End point timeframe
    At baseline (Day 1)
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    275
    255
    Units: Percentage of subjects
    number (confidence interval 95%)
        H44/76 (N=275;255)
    20 (15.1 to 24.8)
    4 (2.2 to 7.6)
        5/99 (N=254;239)
    75 (69 to 80)
    8 (5.2 to 12.6)
        NZ98/254 (N=273;253)
    11 (7.8 to 15.7)
    2 (0.9 to 5.1)
        M10713 (N=274;255)
    57 (51.2 to 63.2)
    56 (49.4 to 61.9)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.1
         upper limit
    		 20.9
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 59.6
         upper limit
    		 72.4
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.9
         upper limit
    		 13.6
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.8
         upper limit
    		 10

    Primary: hSBA Geometric Mean Titers (GMTs) after the last dose of vaccination in the parent study

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    End point title
    		 hSBA Geometric Mean Titers (GMTs) after the last dose of vaccination in the parent study
    End point description
    Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713.
    End point type
    Primary
    End point timeframe
    At 1 month after the last vaccination in parent study and at Day 1
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    275
    255
    Units: Titers
    geometric mean (confidence interval 95%)
        H44/76 (1 month post last vacc.) (N=275;0)
    124 (108 to 143)
    0 (0 to 0)
        H44/76 (Day 1) (N=275;255)
    3.05 (2.61 to 3.56)
    1.2 (1.02 to 1.42)
        5/99 (1 month post last vacc.) (N=254;0)
    270 (234 to 311)
    0 (0 to 0)
        5/99 (Day 1) (N=254;239)
    26 (21 to 31)
    1.57 (1.26 to 1.95)
        NZ98/254 (1 month post last vacc.) (N=273;0)
    22 (19 to 27)
    0 (0 to 0)
        NZ98/254 (Day 1) (N=273;253)
    1.66 (1.46 to 1.89)
    1.11 (0.97 to 1.27)
        M10713 (1 month post last vacc.) (N=271;0)
    19 (16 to 24)
    0 (0 to 0)
        M10713 (Day 1) (N=271;255)
    16 (13 to 20)
    12 (9.86 to 16)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Adjusted geometric mean titers for H44/76 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group ratio
    Point estimate
    2.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.07
         upper limit
    		 3.12
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Adjusted geometric mean titers for 5/99 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group ratio
    Point estimate
    16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12
         upper limit
    		 21
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Adjusted geometric mean titers for NZ98/254 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group ratio
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.26
         upper limit
    		 1.78
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    Adjusted geometric mean titers for M10713 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group ratio
    Point estimate
    1.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.94
         upper limit
    		 1.68

    Primary: Geometric Mean Ratios (GMRs) of GMTs pre-vaccination versus GMTs at Day 1

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    End point title
    		 Geometric Mean Ratios (GMRs) of GMTs pre-vaccination versus GMTs at Day 1 [1] [2]
    End point description
    The GMRs of GMTs at Day 1 versus one month after the last dose of rMenB+OMV NZ vaccination in the parent study were calculated. Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713.
    End point type
    Primary
    End point timeframe
    At Day 1
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.
    End point values
    		 Group 3B
    Number of subjects analysed
    275
    Units: Ratio
    geometric mean (confidence interval 95%)
        H44/76 (N=275)
    0.025 (0.02 to 0.03)
        5/99 (N=254)
    0.098 (0.079 to 0.12)
        NZ98/254 (N=273)
    0.073 (0.059 to 0.089)
        M10713 (N=271)
    0.81 (0.65 to 1.01)
    No statistical analyses for this end point

    Primary: Number of subjects with solicited local and systemic AEs

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    End point title
    		 Number of subjects with solicited local and systemic AEs [3]
    End point description
    Solicited adverse events are signs and symptoms derived from organized data collection systems, such as Subject Diaries or interview. The percentage and frequencies of subjects reporting solicited local and systemic AEs were tabulated. Note: Vaccination 2 was performed only on group B_0_1 subjects.
    End point type
    Primary
    End point timeframe
    7 days (including the day of vaccination) after each vaccination
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary end point was descriptive, no statistical hypothesis test was performed.
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    266
    254
    Units: Subjects
        Any (N=266;254)
    263
    251
        Any Local (vaccination 1) (N=266;253)
    258
    247
        Injection site pain (vaccination 1) (N=264;252)
    258
    247
        Erythema (vaccination 1) (N=261;248)
    54
    18
        Swelling (vaccination 1) (N=261;249)
    60
    34
        Induration (vaccination 1) (N=261;248)
    54
    26
        Any systemic (vaccination 1) (N=266;253)
    203
    163
        Fever (≥ 38.0°C) (vaccination 1) (N=265;253)
    16
    4
        High fever (≥ 39.5°C) (vaccination 1) (N=265;253)
    0
    0
        Nausea (vaccination 1) (N=264;252)
    56
    30
        Fatigue (vaccination 1) (N=266;252)
    155
    110
        Myalgia (vaccination 1) (N=265;252)
    120
    71
        Arthralgia (vaccination 1) (N=265;252)
    84
    47
        Headache (vaccination 1) (N=266;253)
    146
    94
        Any Local (vaccination 2) (N=0;248)
    0
    226
        Injection site pain (vaccination 2) (N=0;247)
    0
    226
        Erythema (vaccination 2) (N=0;247)
    0
    21
        Swelling (vaccination 2) (N=0;248)
    0
    32
        Induration (vaccination 2) (N=0;247)
    0
    31
        Any systemic (vaccination 2) (N=0;248)
    0
    140
        Fever (≥ 38.0°C) (vaccination 2) (N=0;248)
    0
    5
        High fever (≥ 39.5°C) (vaccination 2) (N=0;248)
    0
    0
        Nausea (vaccination 2) (N=0;248)
    0
    33
        Fatigue (vaccination 2) (N=0;248)
    0
    92
        Myalgia (vaccination 2) (N=0;248)
    0
    64
        Arthralgia (vaccination 2) (N=0;248)
    0
    36
        Headache (vaccination 2) (N=0;248)
    0
    84
    No statistical analyses for this end point

    Primary: Number of subjects with any unsolicited adverse events (AEs)

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    End point title
    		 Number of subjects with any unsolicited adverse events (AEs) [4]
    End point description
    An unsolicited adverse event is an adverse event that was not solicited using a Subject Diary and that was spontaneously communicated by a subject and/or parent(s)/legal guardian(s) who has signed the informed consent.
    End point type
    Primary
    End point timeframe
    30 days (including the day of vaccination) after each vaccination
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary end point was descriptive, no statistical hypothesis test was performed.
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    275
    255
    Units: Subjects
        Any (N=275;255)
    87
    131
        Any unsolicited AEs (vaccination 1) (N=275;255)
    87
    96
        Any unsolicited AEs (vaccination 2) (N=0;250)
    0
    73
    No statistical analyses for this end point

    Primary: Number of subjects with any serious adverse events (SAEs), AEs leading to withdrawal and medically attended AEs

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    End point title
    		 Number of subjects with any serious adverse events (SAEs), AEs leading to withdrawal and medically attended AEs [5]
    End point description
    A serious adverse event is any untoward medical occurrence that at any dose results in death or is life threatening or requires prolonged hospitalization, leads to persistent or significant disability/incapacity. The frequencies and percentages of subjects with any SAEs, AEs leading to withdrawal and medically attended AEs were assessed throughout the entire study.
    End point type
    Primary
    End point timeframe
    Average of 1 Month (up to 30 days post first dose)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary end point was descriptive, no statistical hypothesis test was performed.
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    275
    255
    Units: Subjects
        Any SAEs
    0
    1
        Any Medically Attended AEs
    17
    34
        Any AEs leading to premature withdrawal
    0
    1
    No statistical analyses for this end point

    Primary: Number of subjects with any SAEs, AEs leading to withdrawal and medically attended AEs

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    End point title
    		 Number of subjects with any SAEs, AEs leading to withdrawal and medically attended AEs [6]
    End point description
    A serious adverse event is any untoward medical occurrence that at any dose results in death or is life threatening or requires prolonged hospitalization, leads to persistent or significant disability/incapacity.
    End point type
    Primary
    End point timeframe
    Average of 2 Months (up to 30 days after second dose)
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary end point was descriptive, no statistical hypothesis test was performed.
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    275
    255
    Units: Subjects
        Any SAEs
    0
    1
        Any Medically Attended AEs
    17
    34
        Any AEs leading to premature withdrawal
    0
    1
    No statistical analyses for this end point

    Secondary: Percentage of subjects with hSBA ≥ 1:5 at Day 31

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    End point title
    		 Percentage of subjects with hSBA ≥ 1:5 at Day 31
    End point description
    Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713.
    End point type
    Secondary
    End point timeframe
    At Day 31 (30 days post Visit 1)
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    268
    253
    Units: Percentage of subjects
    number (confidence interval 95%)
        H44/76 (N=268;253)
    99 (96.8 to 99.77)
    79 (73.5 to 83.9)
        5/99 (N=226;234)
    100 (98.4 to 100)
    84 (78.9 to 88.6)
        NZ98/254 (N=262;251)
    93 (88.9 to 95.6)
    52 (45.4 to 58.1)
        M10713 (N=268;252)
    99 (96.8 to 99.77)
    87 (82.1 to 90.8)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    20
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 15
         upper limit
    		 25.4
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 vaccine group difference
    Point estimate
    16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.7
         upper limit
    		 21
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 vaccine group difference
    Point estimate
    41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 33.9
         upper limit
    		 47.8
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 vaccine group difference
    Point estimate
    12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8
         upper limit
    		 16.8

    Secondary: Percentage of subjects with hSBA ≥1:8 at Day 31

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    End point title
    		 Percentage of subjects with hSBA ≥1:8 at Day 31
    End point description
    Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713.
    End point type
    Secondary
    End point timeframe
    At Day 31 (30 days post Visit 1)
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    268
    253
    Units: Percentage of subjects
    number (confidence interval 95%)
        H44/76 (N=268;253)
    99 (96.8 to 99.77)
    72 (65.6 to 77)
        5/99 (N=226;234)
    100 (98.4 to 100)
    81 (75.6 to 86)
        NZ98/254 (N=262;251)
    87 (82.8 to 91.2)
    45 (38.4 to 51)
        M10713 (N=268;252)
    98 (95.7 to 99.4)
    85 (79.9 to 89.1)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 21.9
         upper limit
    		 33.3
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.3
         upper limit
    		 24.3
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 35.2
         upper limit
    		 49.9
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.8
         upper limit
    		 18.3

    Secondary: Percentage of subjects with hSBA ≥ 1:16 at Day 31

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    End point title
    		 Percentage of subjects with hSBA ≥ 1:16 at Day 31
    End point description
    Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713.
    End point type
    Secondary
    End point timeframe
    At Day 31 (30 days post booster dose/first dose of vaccination)
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    268
    253
    Units: Percentage of subjects
    number (confidence interval 95%)
        H44/76 (N=268;253)
    99 (96.2 to 99.59)
    58 (52.2 to 64.6)
        5/99 (N=226;234)
    100 (98.4 to 100)
    73 (66.9 to 78.6)
        NZ98/254 (N=262;251)
    79 (73.6 to 83.8)
    36 (29.9 to 42.1)
        M10713 (N=268;252)
    95 (91.8 to 97.4)
    77 (70.9 to 81.7)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    40
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 33.9
         upper limit
    		 46.3
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 21.6
         upper limit
    		 33
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 35.1
         upper limit
    		 50.6
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.9
         upper limit
    		 24.6

    Secondary: hSBA Geometric Mean Titers prior to booster/first dose of vaccination and post booster/first dose of vaccination

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    End point title
    		 hSBA Geometric Mean Titers prior to booster/first dose of vaccination and post booster/first dose of vaccination
    End point description
    Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713.
    End point type
    Secondary
    End point timeframe
    At Day 1 (prior to booster dose/first dose of vaccination) and at Day 31 (30 days post booster dose/first dose of vaccination)
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    268
    253
    Units: Titers
    geometric mean (confidence interval 95%)
        H44/76 prior to booster/1st dose (N=268;253)
    3.1 (2.65 to 3.62)
    1.19 (1.01 to 1.41)
        H44/76 1 month post booster/1st dose (N=268;253)
    188 (155 to 228)
    16 (13 to 20)
        5/99 prior to booster/1st dose (N=211;225)
    24 (19 to 30)
    1.51 (1.21 to 1.88)
        5/99 1 month post booster/1st dose (N=226;234)
    2089 (1690 to 2582)
    31 (25 to 38)
        NZ98/254 prior to booster/1st dose (N=260;249)
    1.64 (1.44 to 1.86)
    1.11 (0.97 to 1.28)
        NZ98/254 1 month post booster/1st dose (N=262;251)
    32 (26 to 39)
    5.39 (4.33 to 6.72)
        M10713 prior to booster/1st dose (N=267;252)
    16 (13 to 20)
    12 (9.62 to 15)
        M10713 1 month post booster/first dose (N=268;252)
    78 (66 to 92)
    30 (25 to 36)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Pre booster/Pre first dose-Adjusted geometric mean titers for H44/76 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group ratios
    Point estimate
    2.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.11
         upper limit
    		 3.2
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Post booster/Post first dose-Adjusted geometric mean titers for H44/76 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group ratios
    Point estimate
    11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.85
         upper limit
    		 15
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Pre booster/Pre first dose-Adjusted geometric mean titers for 5/99 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group ratios
    Point estimate
    16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12
         upper limit
    		 21
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    Post booster/Post first dose-Adjusted geometric mean titers for 5/99 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group ratios
    Point estimate
    68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 51
         upper limit
    		 90
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    Pre booster/Pre first dose-Adjusted geometric mean titers for NZ98/254 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group ratios
    Point estimate
    1.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.24
         upper limit
    		 1.75
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    Post booster dose/first dose-Adjusted geometric mean titers for NZ98/254 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group ratios
    Point estimate
    5.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.49
         upper limit
    		 7.76
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    Pre booster/Pre first dose-Adjusted geometric mean titers for M10713 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group ratios
    Point estimate
    1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.97
         upper limit
    		 1.75
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    Post booster/Post first dose-Adjusted geometric mean titers for M10713 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group ratios
    Point estimate
    2.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.08
         upper limit
    		 3.25

    Secondary: Geometric mean ratio (GMRs) of GMTs one month post vaccination versus pre vaccination at Day 1

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    End point title
    		 Geometric mean ratio (GMRs) of GMTs one month post vaccination versus pre vaccination at Day 1
    End point description
    Bactericidal activity was measured against each of the fout N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713, by calculating the GMRs of GMTs one month post-vaccination of a booster dose versus pre-booster dose (follow-on subjects) or first dose of rMenB+OMV NZ versus pre-first dose (naïve subjects) to each N. meningitidis group B indicator strain.
    End point type
    Secondary
    End point timeframe
    At Day 31 (30 days post booster dose/first dose of vaccination) versus Day 1 (prior to booster dose/first dose of vaccination)
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    268
    253
    Units: Ratio
    geometric mean (confidence interval 95%)
        H44/76 (N=268;253)
    61 (50 to 74)
    14 (11 to 17)
        5/99 (N=211;225)
    87 (67 to 112)
    20 (16 to 26)
        NZ98/254 (N=260;249)
    19 (16 to 24)
    4.92 (3.97 to 6.1)
        M10713 (N=267;252)
    4.85 (4.1 to 5.72)
    2.44 (2.04 to 2.91)
    No statistical analyses for this end point

    Secondary: Percentage of subjects with hSBA ≥ 1:5

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    End point title
    		 Percentage of subjects with hSBA ≥ 1:5
    End point description
    Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713.
    End point type
    Secondary
    End point timeframe
    At Days 4, 8 and 31 (3, 7 and 30 days post booster/second dose of vaccination)
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    242
    203
    Units: Percentage of subjects
    number (confidence interval 95%)
        H44/76 3 days post-vaccination (N=242;105)
    36 (30.3 to 42.8)
    80 (71.1 to 87.2)
        H44/76 7 days post-vaccination (N=242;98)
    98 (95.2 to 99.3)
    99 (94.4 to 99.97)
        H44/76 1 month post-vaccination (N=242;203)
    99 (96.4 to 99.74)
    99 (96.5 to 99.88)
        5/99 3 days post-vaccination (N=185;86)
    78 (71.7 to 84.1)
    83 (72.9 to 89.9)
        5/99 7 days post-vaccination (N=185;88)
    100 (98 to 100)
    99 (93.8 to 99.97)
        5/99 1 month post-vaccination (N=185;174)
    100 (98 to 100)
    99 (95.9 to 99.86)
        NZ98/254 3 days post-vaccination (N=233;105)
    18 (12.9 to 23.1)
    44 (34.1 to 53.8)
        NZ98/254 7 days post-vaccination (N=233;98)
    74 (67.7 to 79.3)
    79 (69.1 to 86.2)
        NZ98/254 1 month post-vaccination (N=233;203)
    93 (88.6 to 95.7)
    76 (69.9 to 82)
        M10713 3 days post-vaccination (N=241;105)
    78 (72.2 to 83.1)
    82 (73.2 to 88.7)
        M10713 7 days post-vaccination (N=241;98)
    98 (94.7 to 99.1)
    96 (89.9 to 98.9)
        M10713 1 month post-vaccination (N=241;203)
    99 (97 to 99.9)
    93 (88.7 to 96.2)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -52.7
         upper limit
    		 -33.1
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.9
         upper limit
    		 3.6
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 2.4
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.6
         upper limit
    		 6.6
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 6.2
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 4.1
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -36.9
         upper limit
    		 -15.7
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.1
         upper limit
    		 5.8
    Statistical analysis title
    		 Statistical analysis 9
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.8
         upper limit
    		 23.3
    Statistical analysis title
    		 Statistical analysis 10
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.4
         upper limit
    		 5.8
    Statistical analysis title
    		 Statistical analysis 11
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.2
         upper limit
    		 7.7
    Statistical analysis title
    		 Statistical analysis 12
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group 3B v Group B_0_1
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.8
         upper limit
    		 10.5

    Secondary: Percentage of subjects with hSBA ≥ 1:8

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    End point title
    		 Percentage of subjects with hSBA ≥ 1:8
    End point description
    Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713.
    End point type
    Secondary
    End point timeframe
    At Days 4, 8 and 31 (3,7 and 30 days post booster/second dose of vaccination)
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    242
    203
    Units: Percentage of subjects
    number (confidence interval 95%)
        H44/76 3 days post-vaccination (N=242;105)
    30 (24.5 to 36.4)
    75 (65.9 to 83.1)
        H44/76 7 days post-vaccination (N=242;98)
    96 (93.1 to 98.3)
    97 (91.3 to 99.4)
        H44/76 1 month post-vaccination (N=242;203)
    99 (96.4 to 99.74)
    98 (95 to 99.5)
        5/99 3 days post-vaccination (N=185;86)
    76 (69.4 to 82.2)
    83 (72.9 to 89.9)
        5/99 7 days post-vaccination (N=185;88)
    100 (98 to 100)
    99 (93.8 to 99.97)
        5/99 1 month post-vaccination (N=185;174)
    100 (98 to 100)
    99 (95.9 to 99.86)
        NZ98/254 3 days post-vaccination (N=233;105)
    16 (11.4 to 21.2)
    42 (32.3 to 51.9)
        NZ98/254 7 days post-vaccination (N=233;98)
    67 (60.1 to 72.6)
    69 (59.3 to 78.3)
        NZ98/254 1 month post-vaccination (N=233;203)
    88 (82.6 to 91.5)
    67 (60.1 to 73.4)
        M10713 3 days post-vaccination (N=241;105)
    70 (63.5 to 75.4)
    73 (63.8 to 81.5)
        M10713 7 days post-vaccination (N=241;98)
    95 (92 to 97.7)
    94 (87.1 to 97.7)
        M10713 1 month post-vaccination (N=241;203)
    98 (95.8 to 99.55)
    90 (85.2 to 93.9)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response measured against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -54.4
         upper limit
    		 -34.3
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.5
         upper limit
    		 5.2
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 3.9
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.9
         upper limit
    		 4.6
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 6.2
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 4.1
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -36.6
         upper limit
    		 -15.7
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.3
         upper limit
    		 8.5
    Statistical analysis title
    		 Statistical analysis 9
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.8
         upper limit
    		 28.3
    Statistical analysis title
    		 Statistical analysis 10
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.4
         upper limit
    		 7.1
    Statistical analysis title
    		 Statistical analysis 11
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.2
         upper limit
    		 8.5
    Statistical analysis title
    		 Statistical analysis 12
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.2
         upper limit
    		 13.2

    Secondary: Percentage of subjects with hSBA ≥ 1:16

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    End point title
    		 Percentage of subjects with hSBA ≥ 1:16
    End point description
    Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713.
    End point type
    Secondary
    End point timeframe
    At Days 4, 8 and 31 (3,7 and 30 days post booster/second dose of vaccination)
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    242
    203
    Units: Percentage of subjects
    number (confidence interval 95%)
        H44/76 3 days post-vaccination (N=242;105)
    21 (15.7 to 26.3)
    50 (40.5 to 60.4)
        H44/76 7 days post-vaccination (N=242;98)
    95 (91 to 97.1)
    92 (84.5 to 96.4)
        H44/76 1 month post-vaccination (N=242;203)
    99 (96.4 to 99.74)
    91 (86.3 to 94.7)
        5/99 3 days post-vaccination (N=185;86)
    70 (63.1 to 76.8)
    76 (65.1 to 84.2)
        5/99 7 days post-vaccination (N=185;88)
    100 (98 to 100)
    99 (93.8 to 99.97)
        5/99 1 month post-vaccination (N=185;174)
    100 (98 to 100)
    98 (95 to 99.64)
        NZ98/254 3 days post-vaccination (N=233;105)
    9 (6 to 13.9)
    30 (21 to 39.2)
        NZ98/254 7 days post-vaccination (N=233;98)
    51 (44.5 to 57.7)
    47 (36.8 to 57.3)
        NZ98/254 1 month post-vaccination (N=233;203)
    81 (75 to 85.6)
    49 (41.7 to 55.9)
        M10713 3 days post-vaccination (N=241;105)
    59 (52 to 64.8)
    64 (53.9 to 73)
        M10713 7 days post-vaccination (N=241;98)
    88 (83.2 to 91.8)
    88 (79.6 to 93.5)
        M10713 1 month post-vaccination (N=241;203)
    95 (91.5 to 97.4)
    84 (78.5 to 89)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -30
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -40.4
         upper limit
    		 -19
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.6
         upper limit
    		 10.3
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.9
         upper limit
    		 12.5
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16
         upper limit
    		 6.5
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 6.2
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.33
         upper limit
    		 5
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -20
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30
         upper limit
    		 -11.1
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.6
         upper limit
    		 15.7
    Statistical analysis title
    		 Statistical analysis 9
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 23.2
         upper limit
    		 40.2
    Statistical analysis title
    		 Statistical analysis 10
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16
         upper limit
    		 6
    Statistical analysis title
    		 Statistical analysis 11
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.8
         upper limit
    		 8.9
    Statistical analysis title
    		 Statistical analysis 12
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.3
         upper limit
    		 16.9

    Secondary: hSBA Geometric Mean Titers prior to booster/second dose of vaccination & post booster/second dose of vaccination

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    End point title
    		 hSBA Geometric Mean Titers prior to booster/second dose of vaccination & post booster/second dose of vaccination
    End point description
    Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713.
    End point type
    Secondary
    End point timeframe
    At Day 1 (prior to booster and second dose of vaccination) and at Days 4, 8, 31 (3,7 and 30 days post booster/second dose of vaccination)
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    242
    203
    Units: Titers
    geometric mean (confidence interval 95%)
        H44/76 pre-vaccination (N=242;203)
    2.99 (2.41 to 3.7)
    17 (14 to 22)
        H44/76 3 days post-vaccination (N=242;105)
    3.2 (2.6 to 3.94)
    17 (13 to 23)
        H44/76 7 days post-vaccination (N=242;98)
    115 (98 to 136)
    57 (44 to 73)
        H44/76 1 month post-vaccination (N=242;203)
    196 (170 to 228)
    56 (48 to 66)
        5/99 pre-vaccination (N=175;169)
    24 (18 to 32)
    31 (23 to 41)
        5/99 3 days post-vaccination (N=185;86)
    24 (18 to 31)
    27 (19 to 41)
        5/99 7 days post-vaccination (N=185;88)
    1787 (1477 to 2162)
    337 (257 to 442)
        5/99 1 month post-vaccination (N=185;174)
    2026 (1714 to 2395)
    248 (208 to 295)
        NZ98/254 pre-vaccination (N=231;201)
    1.57 (1.29 to 1.92)
    5.11 (4.1 to 6.38)
        NZ98/254 3 days post-vaccination (N=233;105)
    1.62 (1.35 to 1.96)
    4.45 (3.38 to 5.84)
        NZ98/254 7 days post-vaccination (N=233;98)
    12 (10 to 15)
    12 (8.46 to 16)
        NZ98/254 1 month post-vaccination (N=233;203)
    35 (29 to 42)
    14 (11 to 17)
        M10713 pre-vaccination (N=240;202)
    15 (12 to 19)
    32 (25 to 41)
        M10713 3 days post-vaccination (N=241;105)
    16 (13 to 21)
    23 (17 to 33)
        M10713 7 days post-vaccination (N=241;98)
    54 (46 to 62)
    45 (36 to 57)
        M10713 1 month post-vaccination (N=241;203)
    78 (67 to 92)
    41 (35 to 49)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Adjusted geometric mean titers for H44/76 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group difference
    Point estimate
    3.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.85
         upper limit
    		 4.29
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Adjusted geometric mean titers for 5/99 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group difference
    Point estimate
    8.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.51
         upper limit
    		 10
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Adjusted geometric mean titers for NZ98/254 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group difference
    Point estimate
    2.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.98
         upper limit
    		 3.36
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    Adjusted geometric mean titers for M10713 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANOVA
    Parameter type
    		 Vaccine group difference
    Point estimate
    1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.52
         upper limit
    		 2.36

    Secondary: Geometric Mean Ratios (GMRs) of GMTs post booster/second vaccination versus prior to booster/second vaccination

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    End point title
    		 Geometric Mean Ratios (GMRs) of GMTs post booster/second vaccination versus prior to booster/second vaccination
    End point description
    Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713, by calculating the GMRs of GMTs post-vaccination with a booster dose (Group 3B) versus pre-booster dose or second dose (Group B_0_1) of vaccination versus pre-second dose.
    End point type
    Secondary
    End point timeframe
    At Day 31 (30 days post booster/second dose of vaccination)
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    242
    203
    Units: Ratio
    geometric mean (confidence interval 95%)
        H44/76 (N=242;203)
    66 (55 to 79)
    3.27 (2.66 to 4.03)
        5/99 (N=175;169)
    85 (65 to 111)
    8.1 (6.12 to 11)
        NZ98/25 (N=231;201)
    22 (19 to 27)
    2.63 (2.15 to 3.21)
        M10713 (N=240;202)
    5.07 (4.33 to 5.94)
    1.27 (1.07 to 1.52)
    No statistical analyses for this end point

    Secondary: Percentage of subjects with four-fold rise pre-compared to 3, 7, 30 days post-vaccination with a booster dose (follow-on subjects) or second dose (naive subjects) of vaccination, to each and any one, two, three or all four indicator strains

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    End point title
    		 Percentage of subjects with four-fold rise pre-compared to 3, 7, 30 days post-vaccination with a booster dose (follow-on subjects) or second dose (naive subjects) of vaccination, to each and any one, two, three or all four indicator strains
    End point description
    Percentage of subjects with four-fold rise in hSBA titers relative to baseline were defined as: for a pre-vaccination titer < 4, a post-vaccination titer of at least 16; for a pre-vaccination titer ≥ 4 but < LLOQ, a post vaccination titer of at least fourfold the LLOQ; for a pre-vaccination titer ≥ LLOQ, a post vaccination titer of at least four-fold the pre-vaccination titer.
    End point type
    Secondary
    End point timeframe
    At Days 4,8 and 31 (3,7 and 30 days post booster/second dose of vaccination)
    End point values
    		 Group 3B Group B_0_1
    Number of subjects analysed
    242
    203
    Units: Percentage of subjects
    number (confidence interval 95%)
        H44/76 3 days post-vaccination (N=242;105)
    2 (0.7 to 4.8)
    4 (1 to 9.5)
        H44/76 7 days post-vaccination (N=242;98)
    88 (82.8 to 91.5)
    35 (25.4 to 45)
        H44/76 1 month post-vaccination (N=242;203)
    96 (93.1 to 98.3)
    38 (31.7 to 45.5)
        5/99 3 days post-vaccination (N=175;83)
    5 (2 to 8.8)
    6 (2 to 13.5)
        5/99 7 days post-vaccination (N=175;86)
    97 (92.7 to 98.7)
    59 (48.2 to 69.8)
        5/99 1 month post-vaccination (N=175;169)
    97 (93.5 to 99.1)
    64 (56.8 to 71.7)
        NZ98/254 3 days post-vaccination (N=231;104)
    2 (0.7 to 5)
    2 (0.23 to 6.8)
        NZ98/254 7 days post-vaccination (N=231;97)
    55 (48.3 to 61.5)
    19 (11.4 to 27.7)
        NZ98/254 1 month post-vaccination (N=231;201)
    81 (75.3 to 85.8)
    27 (21.3 to 34.1)
        M10713 3 days post-vaccination (N=240;105)
    3 (0.9 to 5.4)
    0 (0 to 3.5)
        M10713 7 days post-vaccination (N=240;97)
    34 (27.8 to 40.1)
    6 (2.3 to 13)
        M10713 1 month post-vaccination (N=240;202)
    49 (42.3 to 55.3)
    9 (5.8 to 14.3)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.5
         upper limit
    		 1.8
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 42.1
         upper limit
    		 62.5
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 50.5
         upper limit
    		 64.7
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.1
         upper limit
    		 4
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 27
         upper limit
    		 48.1
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 25.2
         upper limit
    		 40.4
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.7
         upper limit
    		 3.4
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 25.6
         upper limit
    		 45.7
    Statistical analysis title
    		 Statistical analysis 9
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 45.2
         upper limit
    		 61.1
    Statistical analysis title
    		 Statistical analysis 10
    Statistical analysis description
    3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 5.4
    Statistical analysis title
    		 Statistical analysis 11
    Statistical analysis description
    7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 19.1
         upper limit
    		 34.9
    Statistical analysis title
    		 Statistical analysis 12
    Statistical analysis description
    1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.
    Comparison groups
    Group B_0_1 v Group 3B
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen score method
    Parameter type
    		 Vaccine group difference
    Point estimate
    39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 31.6
         upper limit
    		 46.6

    Secondary: Percentage of subjects with hSBA ≥ 1:5

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    End point title
    		 Percentage of subjects with hSBA ≥ 1:5 [7]
    End point description
    Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713. Only subjects receiving a second vaccination (group B_0_1) were assessed for this outcome measure.
    End point type
    Secondary
    End point timeframe
    At Day 31 (30 days post second dose of vaccination)
    Notes
    [7] - 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: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.
    End point values
    		 Group B_0_1
    Number of subjects analysed
    215
    Units: Percentage of subjects
    number (confidence interval 95%)
        H44/76 (N=215)
    99 (96.7 to 99.89)
        5/99 (N=195)
    98 (95.6 to 99.68)
        NZ98/254 (N=215)
    77 (70.5 to 82.2)
        M10713 (N=214)
    93 (88.7 to 96)
    No statistical analyses for this end point

    Secondary: Percentage of subjects with hSBA ≥1:8

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    End point title
    		 Percentage of subjects with hSBA ≥1:8 [8]
    End point description
    Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713. Only subjects receiving a second vaccination (group B_0_1) were assessed for this outcome measure.
    End point type
    Secondary
    End point timeframe
    At Day 31 (30 days post second vaccination)
    Notes
    [8] - 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: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.
    End point values
    		 Group B_0_1
    Number of subjects analysed
    215
    Units: Percentage of subjects
    number (confidence interval 95%)
        H44/76 (N=215)
    98 (95.3 to 99.5)
        5/99 (N=195)
    98 (95.6 to 99.68)
        NZ98/254 (N=215)
    67 (60.3 to 73.2)
        M10713 (N=214)
    90 (85.4 to 93.8)
    No statistical analyses for this end point

    Secondary: Percentage of subjects with hSBA ≥1:16

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    End point title
    		 Percentage of subjects with hSBA ≥1:16 [9]
    End point description
    Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713. Only subjects receiving a second vaccination (group B_0_1) were assessed for this outcome measure.
    End point type
    Secondary
    End point timeframe
    At Day 31 (30 days post second vaccination)
    Notes
    [9] - 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: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.
    End point values
    		 Group B_0_1
    Number of subjects analysed
    215
    Units: Percentage of subjects
    number (confidence interval 95%)
        H44/76 (N=215)
    91 (86 to 94.2)
        5/99 (N=195)
    98 (94.8 to 99.4)
        NZ98/254 (N=215)
    48 (41.5 to 55.3)
        M10713 (N=214)
    84 (78.5 to 88.7)
    No statistical analyses for this end point

    Secondary: hSBA Geometric Mean Titers (GMTs) post second dose of vaccination

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    End point title
    		 hSBA Geometric Mean Titers (GMTs) post second dose of vaccination [10]
    End point description
    Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713. Only subjects receiving a second vaccination (group B_0_1) were assessed for this outcome measure.
    End point type
    Secondary
    End point timeframe
    At Day 1 and Day 31 (30 days post second dose of vaccination)
    Notes
    [10] - 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: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.
    End point values
    		 Group B_0_1
    Number of subjects analysed
    215
    Units: Titers
    geometric mean (confidence interval 95%)
        H44/76 Day 1 (N=215)
    1.32 (1.18 to 1.47)
        H44/76 1 month post 2nd vaccination (N=215)
    61 (53 to 70)
        5/99 Day 1 (N=181)
    1.63 (1.35 to 1.96)
        5/99 1 month post 2nd vaccination (N=195)
    257 (217 to 305)
        NZ98/254 Day 1 (N=213)
    1.28 (1.15 to 1.42)
        NZ98/254 1 month post 2nd vaccination (N=215)
    14 (11 to 17)
        M10713 Day 1 (N=214)
    14 (11 to 18)
        M10713 1 month post 2nd vaccination (N=214)
    46 (38 to 55)
    No statistical analyses for this end point

    Secondary: Geometric mean ratio (GMRs) of GMTs one month post second vaccination versus pre vaccination at Day 1

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    End point title
    		 Geometric mean ratio (GMRs) of GMTs one month post second vaccination versus pre vaccination at Day 1 [11]
    End point description
    Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 and M10713. Only subjects receiving a second vaccination (group B_0_1) were assessed for this outcome measure.
    End point type
    Secondary
    End point timeframe
    At Day 1 and Day 31 (30 days post 2nd vaccination)
    Notes
    [11] - 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: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.
    End point values
    		 Group B_0_1
    Number of subjects analysed
    215
    Units: Ratio
    geometric mean (confidence interval 95%)
        H44/76 (N=215)
    46 (39 to 54)
        5/99 (N=181)
    156 (117 to 209)
        NZ98/254 (N=213)
    11 (8.88 to 14)
        M10713 (N=214)
    3.23 (2.76 to 3.77)
    No statistical analyses for this end point

    Secondary: Percentage of subjects with four-fold rise pre-vaccination with a first dose compared to one month post-vaccination with a second dose (naïve subjects) of rMenB+OMV NZ, to each and any one, two, three or all 4 indicator strains

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    End point title
    		 Percentage of subjects with four-fold rise pre-vaccination with a first dose compared to one month post-vaccination with a second dose (naïve subjects) of rMenB+OMV NZ, to each and any one, two, three or all 4 indicator strains [12]
    End point description
    Percentage of subjects with four-fold rise in hSBA titers relative to baseline were defined as: for a pre-vaccination titer < 4, a post-vaccination titer of at least 16; for a pre-vaccination titer ≥ 4 but < LLOQ, a post vaccination titer of at least fourfold the LLOQ; for a pre-vaccination titer ≥ LLOQ, a post vaccination titer of at least fourfold the pre-vaccination titer. Only subjects receiving the second dose of vaccination(group B_0_1) were considered for this outcome measure.
    End point type
    Secondary
    End point timeframe
    At Day 31 (30 days post second dose of vaccination)
    Notes
    [12] - 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: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.
    End point values
    		 Group B_0_1
    Number of subjects analysed
    98
    Units: Percentage of subjects
    number (confidence interval 95%)
        H44/76 (N=98)
    97 (91.3 to 99.4)
        5/99 (N=86)
    100 (95.8 to 100)
        NZ98/254 (N=98)
    64 (54 to 73.7)
        M10713 (N=98)
    37 (27.2 to 47.1)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Solicited AEs were collected until 7 days after vaccinations. Unsolicited AEs were collected 30 days after vaccination at Visit 1 (all subjects) and at Visit 3 (naïve subjects only).
    Adverse event reporting additional description
    Serious Adverse Events (SAEs) were collected until study termination (1 month for follow-on subjects/2 months for naïve subjects).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Group 3B
    Reporting group description
    		 Subjects who received a third dose booster of rMenB+OMV NZ at 4 to 7.5 years after the last dose received during studies V72P10 (NCT00661713) or V72_41(NCT0142384), and had blood collected at baseline and at 3, 7 and 30 days after the third dose booster.

    Reporting group title
    Group B_0_1
    Reporting group description
    		 Subjects who received two doses of rMenB+OMV NZ at a 0 and 1 month schedule and had blood collected at baseline, 30 days after the first dose and 3 or 7, and 30 days after the second dose.

    Serious adverse events
    		 Group 3B Group B_0_1
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 275 (0.00%)
    1 / 255 (0.39%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 275 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Group 3B Group B_0_1
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    266 / 275 (96.73%)
    253 / 255 (99.22%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    150 / 275 (54.55%)
    126 / 255 (49.41%)
         occurrences all number
    361
    442
    General disorders and administration site conditions
    Injectioon site pain
         subjects affected / exposed
    259 / 275 (94.18%)
    251 / 255 (98.43%)
         occurrences all number
    1088
    2029
    Injection site erythema
         subjects affected / exposed
    162 / 275 (58.91%)
    135 / 255 (52.94%)
         occurrences all number
    575
    724
    Fatigue
         subjects affected / exposed
    156 / 275 (56.73%)
    141 / 255 (55.29%)
         occurrences all number
    394
    489
    Injection site induration
         subjects affected / exposed
    135 / 275 (49.09%)
    136 / 255 (53.33%)
         occurrences all number
    548
    834
    Injection site swelling
         subjects affected / exposed
    123 / 275 (44.73%)
    111 / 255 (43.53%)
         occurrences all number
    475
    675
    Pyrexia
         subjects affected / exposed
    17 / 275 (6.18%)
    9 / 255 (3.53%)
         occurrences all number
    22
    16
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    56 / 275 (20.36%)
    53 / 255 (20.78%)
         occurrences all number
    113
    128
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    121 / 275 (44.00%)
    100 / 255 (39.22%)
         occurrences all number
    291
    313
    Arthralgia
         subjects affected / exposed
    85 / 275 (30.91%)
    63 / 255 (24.71%)
         occurrences all number
    203
    212
    Infections and infestations
    Viral upper respiratory tract infection
         subjects affected / exposed
    13 / 275 (4.73%)
    23 / 255 (9.02%)
         occurrences all number
    13
    26

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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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