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    Clinical Trial Results:
    A Phase II, Randomized, Open label, Multi-center Study to Assess the Immunogenicity and Safety of Meningococcal ABCWY Vaccine and of rMenB+OMV NZ and MenACWY Administered Concomitantly in the Same Arm, in Two Separate Arms, or Alone in Healthy Adults 10-25 Years of Age

    Summary
    EudraCT number
    		 2017-005128-12
    Trial protocol
    		 CZ  
    Global end of trial date
    05 Jul 2019

    Results information
    Results version number
    		 v2(current)
    This version publication date
    26 Feb 2020
    First version publication date
    22 Dec 2019
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    208205
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03587207
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 V102_19: Novartis Identifier
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    GSK Response Center, GlaxoSmithKline, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 044 2089-904466, 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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    06 Sep 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    19 Dec 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Jul 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the immune response to 2 doses of MenABCWY, rMenB+OMV NZ, or rMenB+OMV NZ and MenACWY administered concomitantly in the same arm or in 2 different arms, and to a single dose of MenACWY at 1 month after the last vaccination
    Protection of trial subjects
    All subjects were observed for at least 30 minutes after the administration of vaccines with appropriate medical treatment readily available in case of anaphylaxis. Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects who had no contraindications to any components of the vaccine. Subjects were followed-up until 30 days after the last vaccination.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Jul 2018
    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
    Czech Republic: 520
    Worldwide total number of subjects
    520
    EEA total number of subjects
    520
    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)
    67
    Adolescents (12-17 years)
    189
    Adults (18-64 years)
    264
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Subjects were recruited from 1 center at Czechia.

    Pre-assignment
    Screening details
    		 Out of the total 520 subjects enrolled in this study, 500 subjects received the vaccination. Among the 20 subjects that were not vaccinated, 15 did not fuflill eligibility criteria and 5 were excluded due to other reasons.

    Pre-assignment period milestones
    Number of subjects started
    		 520
    Number of subjects completed
    		 500

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Other reasons: 5
    Reason: Number of subjects
    		 Eligibility criteria not fulfilled: 15
    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MenABCWY Group
    Arm description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of MenABCWY twice, 2 months apart (Day 1 and Day 61).
    Arm type
    		 Experimental

    Investigational medicinal product name
    MenABCWY vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and suspension for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Two doses administered intramuscularly in the deltoid region of the non-dominant arm.

    Arm title
    		 rMenBOMV+ACWY_S Group
    Arm description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) concomitantly received one dose of rMenB+OMV NZ (Bexsero) and one dose of MenACWY (Menveo) in the same arm twice, 2 months apart (Day 1 and Day 61).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    rMenB+OMV NZ (Bexsero) vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Two doses administered 2 months apart intramuscularly in the deltoid region of the non-dominant arm to subjects randomized to the rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group and rMenBOMV Group

    Investigational medicinal product name
    MenACWY vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Two doses administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomized to the rMenBOMV+ACWY_S Group and rMenBOMV+ACWY_D Group and one dose administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomized to the MenACWY Group

    Arm title
    		 rMenBOMV+ACWY_D Group
    Arm description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) concomitantly received one dose of rMenB+OMV NZ (Bexsero) and one dose of MenACWY (Menveo) in 2 different arms twice, 2 months apart (Day 1 and Day 61).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    rMenB+OMV NZ (Bexsero) vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Two doses administered 2 months apart intramuscularly in the deltoid region of the non-dominant arm to subjects randomized to the rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group and rMenBOMV Group

    Investigational medicinal product name
    MenACWY vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Two doses administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomized to the rMenBOMV+ACWY_S Group and rMenBOMV+ACWY_D Group and one dose administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomized to the MenACWY Group

    Arm title
    		 rMenBOMV Group
    Arm description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of rMenB+OMV NZ (Bexsero) twice, 2 months apart (Day 1 and Day 61).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    rMenB+OMV NZ (Bexsero) vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Two doses administered 2 months apart intramuscularly in the deltoid region of the non-dominant arm to subjects randomized to the rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group and rMenBOMV Group

    Arm title
    		 MenACWY Group
    Arm description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of MenACWY (Menveo) once at Day 1, which was the first and last vaccination for MenACWY group.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    MenACWY vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Two doses administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomized to the rMenBOMV+ACWY_S Group and rMenBOMV+ACWY_D Group and one dose administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomized to the MenACWY Group

    Number of subjects in period 1 [1]
    		MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group MenACWY Group
    Started
    100
    104
    100
    94
    102
    Completed
    100
    104
    100
    94
    102
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The number of subjects reported in the baseline period represent the total exposed set (500), which is different to the worldwide enrolled set (520)

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MenABCWY Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of MenABCWY twice, 2 months apart (Day 1 and Day 61).

    Reporting group title
    rMenBOMV+ACWY_S Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) concomitantly received one dose of rMenB+OMV NZ (Bexsero) and one dose of MenACWY (Menveo) in the same arm twice, 2 months apart (Day 1 and Day 61).

    Reporting group title
    rMenBOMV+ACWY_D Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) concomitantly received one dose of rMenB+OMV NZ (Bexsero) and one dose of MenACWY (Menveo) in 2 different arms twice, 2 months apart (Day 1 and Day 61).

    Reporting group title
    rMenBOMV Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of rMenB+OMV NZ (Bexsero) twice, 2 months apart (Day 1 and Day 61).

    Reporting group title
    MenACWY Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of MenACWY (Menveo) once at Day 1, which was the first and last vaccination for MenACWY group.

    Reporting group values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group MenACWY Group Total
    Number of subjects
    		 100 104 100 94 102 500
    Age categorical
    Units: Subjects
        Children and Adolescents (10-17 years)
    		 53 50 48 49 50 250
        Adults (18-25 years)
    		 47 54 52 45 52 250
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 17.1 ( 4.34 ) 16.9 ( 4.28 ) 17.1 ( 4.49 ) 17.4 ( 4.64 ) 17.1 ( 4.57 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 47 48 49 53 49 246
        Male
    		 53 56 51 41 53 254
    Race/Ethnicity, Customized
    Units: Subjects
        WHITE
    		 100 104 100 94 102 500

    End points

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    End points reporting groups
    Reporting group title
    MenABCWY Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of MenABCWY twice, 2 months apart (Day 1 and Day 61).

    Reporting group title
    rMenBOMV+ACWY_S Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) concomitantly received one dose of rMenB+OMV NZ (Bexsero) and one dose of MenACWY (Menveo) in the same arm twice, 2 months apart (Day 1 and Day 61).

    Reporting group title
    rMenBOMV+ACWY_D Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) concomitantly received one dose of rMenB+OMV NZ (Bexsero) and one dose of MenACWY (Menveo) in 2 different arms twice, 2 months apart (Day 1 and Day 61).

    Reporting group title
    rMenBOMV Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of rMenB+OMV NZ (Bexsero) twice, 2 months apart (Day 1 and Day 61).

    Reporting group title
    MenACWY Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of MenACWY (Menveo) once at Day 1, which was the first and last vaccination for MenACWY group.

    Primary: human Serum Bactericidal Activity (hSBA) Adjusted Geometric Mean Titers (GMTs) against all of N. meningitidis serogroup B test strains (pooled), one month after last vaccination.

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    End point title
    		 human Serum Bactericidal Activity (hSBA) Adjusted Geometric Mean Titers (GMTs) against all of N. meningitidis serogroup B test strains (pooled), one month after last vaccination. [1]
    End point description
    hSBA titers against all of N. meningitidis serogroup B test strains were calculated in terms of GMTs. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). The serogroup B strains were grouped together to perform a pooled analysis. Adjusted means were obtained from ANCOVA model fitted to all of the Serogroup B test strains, study group, test strain and center as fixed effects; zero-centered pre-vaccination log-transformed titer was included as a continuous covariate. Analysis was performed on PPS for immunogenicity that included subjects who had no major protocol violations and whose assay results were available for at least 1 serogroup or B strain at Day 91 for all study groups except for MenACWY group that was not considered for this analysis as only serogroup B strains were assessed in this outcome measure.
    End point type
    Primary
    End point timeframe
    1 month after last vaccination i.e.: at Day 91 for all groups except for the MenACWY Group
    Notes
    [1] - 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: MenACWY group was not considered for this analysis as only serogroup B strains were assessed in this outcome measure.
    End point values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group
    Number of subjects analysed
    98
    100
    97
    90
    Units: titers
        geometric mean (confidence interval 80%)
    31.84 (28.18 to 35.98)
    38.48 (34.23 to 43.26)
    40.08 (35.44 to 45.33)
    42.38 (37.31 to 48.13)
    Statistical analysis title
    		 Immune interference-Pooled B strains
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the pooled B strains, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    		 [2]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.96
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.1
    Notes
    [2] - rMenBOMV+ACWY_S is to be declared statistically inferior if the 2-sided 80% CIs of the between group ratio of the GMT with rMenBOMV+ACWY_D as control is lower than 1 at 1 month after last vaccination. The following ANCOVA model is used: fixed-effect model including age strata, study group, strain and center as fixed effects. The pre vaccination (Baseline) log-transformed titer with centering at zero is included as a continuous covariate.

    Primary: hSBA Adjusted GMTs against each of the N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, one month after last vaccination

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    End point title
    		 hSBA Adjusted GMTs against each of the N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, one month after last vaccination
    End point description
    hSBA titers against each of the N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y were calculated in terms of GMTs. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). Adjusted means were obtained from ANCOVA model fitted to each Serogroup (Strain) individually, study group and center as fixed effects and zero-centered pre-vaccination log-transformed titer as a continuous covariate. Analysis was performed on PPS for immunogenicity that included subjects who had no major protocol violations and whose assay results were available for at least 1 serogroup or B strain at Day 91 for all study groups except MenACWY Group or at Day 31 for the MenACWY Group.
    End point type
    Primary
    End point timeframe
    1 month after last vaccination i.e.: at Day 91 for all groups except the MenACWY Group, and at Day 31 for the MenACWY Group.
    End point values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group MenACWY Group
    Number of subjects analysed
    98
    101
    97
    90
    97
    Units: titers
    geometric mean (confidence interval 80%)
        M14459 (N-97,100,96,90,97)
    23.91 (20.52 to 27.86)
    23.34 (20.16 to 27.01)
    23.23 (19.91 to 27.10)
    22.87 (19.52 to 26.80)
    2.48 (2.13 to 2.89)
        96217 (N-98,100,97,90,96)
    81.09 (69.24 to 94.97)
    102.68 (88.24 to 119.50)
    97.54 (83.18 to 114.39)
    113.54 (96.25 to 133.93)
    4.15 (3.54 to 4.86)
        NZ98/254 (N-98,100,97,89,97)
    12.97 (10.89 to 15.45)
    16.39 (13.86 to 19.39)
    21.12 (17.71 to 25.18)
    20.97 (17.47 to 25.16)
    2.15 (1.81 to 2.57)
        M07-0241084(N-98,100,96,89,95)
    13.08 (11.09 to 15.43)
    18.00 (15.35 to 21.11)
    22.59 (19.12 to 26.69)
    25.34 (21.30 to 30.13)
    4.08 (3.45 to 4.82)
        Meningitis A(N-97,101,97,90,93)
    104.90 (87.02 to 126.47)
    187.52 (156.94 to 224.05)
    204.01 (169.06 to 246.18)
    94.91 (78.26 to 115.12)
    52.03 (43.01 to 62.95)
        Meningitis C (N-98,100,97,90,97)
    172.99 (140.43 to 213.09)
    144.80 (118.48 to 176.97)
    145.42 (117.91 to 179.34)
    32.01 (25.75 to 39.79)
    34.66 (28.09 to 42.78)
        Meningitis W(98,100,96,90,97)
    260.11 (219.31 to 308.51)
    245.63 (208.40 to 289.52)
    254.20 (213.76 to 302.30)
    193.58 (161.68 to 231.76)
    80.11 (67.42 to 95.19)
        Meningitis Y(N-97,100,97,89,96)
    219.52 (173.10 to 278.39)
    186.08 (148.25 to 233.55)
    204.92 (161.40 to 260.16)
    3.66 (2.86 to 4.69)
    92.41 (72.75 to 117.37)
    Statistical analysis title
    		 Immune interference-M14459 strain
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis B M14459 (fHbp) strain, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 [3]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.2
    Notes
    [3] - M14459 strain-Between group ratios for comparison of rMenBOMV+ACWY_S and rMenBOMV+ACWY_D groups
    Statistical analysis title
    		 Immune interference- 96217 strain
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis B 96217 (NadA) strain, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 [4]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.05
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.26
    Notes
    [4] - 96217 strain-Between group ratios for comparison of rMenBOMV+ACWY_S and rMenBOMV+ACWY_D groups
    Statistical analysis title
    		 Immune interference-NZ98/254 strain
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis B NZ98/254 (PorA) strain, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 [5]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.78
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 0.95
    Notes
    [5] - NZ98/254 strain-Between group ratios for comparison of rMenBOMV+ACWY_S and rMenBOMV+ACWY_D groups
    Statistical analysis title
    		 Immune interference-M07-0241084 strain
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis B M07-0241084 (NHBA) strain, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 [6]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.8
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 0.96
    Notes
    [6] - M07-0241084 strain- Between group ratios for comparison of rMenBOMV_ACWY_S group and rMenBOMV+ACWY_D group
    Statistical analysis title
    		 Immune interference-Serogroup A
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis serogroup A, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 [7]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.92
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.14
    Notes
    [7] - Serogroup A- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group
    Statistical analysis title
    		 Immune interference-Serogroup C
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis serogroup C, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 [8]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.27
    Notes
    [8] - Serogroup C- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group
    Statistical analysis title
    		 Immune interference-Serogroup W
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis serogroup W, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 [9]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.97
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.18
    Notes
    [9] - Serogroup W- Between group ratios for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group
    Statistical analysis title
    		 Immune interference-Serogroup Y
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis serogroup Y, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 [10]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.91
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.19
    Notes
    [10] - Serogroup Y- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group
    Statistical analysis title
    		 Other unknown interference-M14459 strain
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B M14459 (fHbp) strain, one month after last vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [11]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.02
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.22
    Notes
    [11] - M14459 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Other unknown interference-96217 strain
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B 96217 (NadA)strain, one month after last vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [12]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.79
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 0.95
    Notes
    [12] - 96217 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Other unknown interference-NZ98/254
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B NZ98/254 (PorA) strain, one month after last vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [13]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.79
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 0.97
    Notes
    [13] - NZ98/254 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Other unknown interference-M07-0241084
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B M07-0241084 (NHBA) strain, one month after last vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [14]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.73
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 0.88
    Notes
    [14] - M07-0241084 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Other unknown interference-serogroup A
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogrpoup A, one month after last vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [15]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.56
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 0.69
    Notes
    [15] - Serogroup A- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Other unknown interference-Serogroup C
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogroup C, one month after last vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [16]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.19
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.94
         upper limit
    		 1.52
    Notes
    [16] - Serogroup C- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Other unknown interference-Serogroup W
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogroup W, one month after last vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [17]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.06
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.29
    Notes
    [17] - Serogroup W- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Other unknown interference-Serogroup Y
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogroup Y, one month after last vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [18]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.18
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.55
    Notes
    [18] - Serogroup Y- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Immune response effects-M14459 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_S versus rMenBOMV study groups, on the Meningitis B M14459(fHbp) strain, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV Group
    Number of subjects included in analysis
    191
    Analysis specification
    Pre-specified
    Analysis type
    		 [19]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.02
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.22
    Notes
    [19] - M14459 strain- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV group.
    Statistical analysis title
    		 Immune response effects-96217 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_S versus rMenBOMV study groups, on the Meningitis B 96217 (NadA) strain, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV Group
    Number of subjects included in analysis
    191
    Analysis specification
    Pre-specified
    Analysis type
    		 [20]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.9
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.09
    Notes
    [20] - 96217 strain-Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV group.
    Statistical analysis title
    		 Immune response effects-NZ98/254 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_S versus rMenBOMV study groups, on the Meningitis B NZ98/254 (PorA) strain, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV Group
    Number of subjects included in analysis
    191
    Analysis specification
    Pre-specified
    Analysis type
    		 [21]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.78
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 0.96
    Notes
    [21] - NZ98/254 strain-Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV group.
    Statistical analysis title
    		 Immune response effects-M07-0241084 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_S versus rMenBOMV study groups, on the Meningitis B M07-0241084 (NHBA) strain, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV Group
    Number of subjects included in analysis
    191
    Analysis specification
    Pre-specified
    Analysis type
    		 [22]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.71
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 0.86
    Notes
    [22] - M07-0241084 strain-Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV group.
    Statistical analysis title
    		 Immune response effects-Serogroup A
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_S versus MenACWY study groups, on the Meningitis serogroup A, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v MenACWY Group
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 [23]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    3.6
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 2.9
         upper limit
    		 4.47
    Notes
    [23] - Serogroup A- Between group ratio for comparison of rMenBOMV+ACWY_S group and MenACWY group.
    Statistical analysis title
    		 Immune response effects-Serogroup C
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_S versus MenACWY study groups, on the Meningitis serogroup C, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v MenACWY Group
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 [24]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    4.18
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 3.28
         upper limit
    		 5.31
    Notes
    [24] - Serogroup C- Between group ratio for comparison of rMenBOMV+ACWY_S group and MenACWY group.
    Statistical analysis title
    		 Immune response effects-Serogroup W
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_S versus MenACWY study groups, on the Meningitis serogroup W, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v MenACWY Group
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 [25]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    3.07
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 2.52
         upper limit
    		 3.73
    Notes
    [25] - Serogroup W- Between group ratio for comparison of rMenBOMV+ACWY_S group and MenACWY group.
    Statistical analysis title
    		 Immune response effects-Serogroup Y
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_S versus MenACWY study groups, on the Meningitis serogroup Y, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v MenACWY Group
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 [26]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    2.01
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 1.53
         upper limit
    		 2.65
    Notes
    [26] - Serogroup Y- Between group ratio for comparison of rMenBOMV+ACWY_S group and MenACWY group.
    Statistical analysis title
    		 Immune response effects-M14459 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_D versus rMenBOMV study groups, on the Meningitis B M14459 (fHbp) strain, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_D Group v rMenBOMV Group
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 [27]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.02
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.22
    Notes
    [27] - M14459 strain- Between group ratio for comparison of rMenBOMV+ACWY_D group and rMenBOMV group.
    Statistical analysis title
    		 Immune response effects-96217 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_D versus rMenBOMV study groups, on the Meningitis B 96217 (NadA) strain, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_D Group v rMenBOMV Group
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 [28]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.86
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.04
    Notes
    [28] - 96217 strain- Between group ratios for comparison of rMenBOMV+ACWY_D group and rMenBOMV group
    Statistical analysis title
    		 Immune response effects-NZ98/254 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_D versus rMenBOMV study groups, on the Meningitis B NZ98/254 (PorA) strain, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_D Group v rMenBOMV Group
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 [29]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.01
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 1.24
    Notes
    [29] - NZ98/254 strain-Between group ratio for comparison of rMenBOMV+ACWY_D group and rMenBOMV group.
    Statistical analysis title
    		 Immune response effect-M07-0241084 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_D versus rMenBOMV study groups, on the Meningitis B M07-0241084 (NHBA) strain, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_D Group v rMenBOMV Group
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 [30]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.89
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.09
    Notes
    [30] - M07-0241084 strain-Between group ratio for comparison of rMenBOMV+ACWY_D group and rMenBOMV group.
    Statistical analysis title
    		 Immune response effects- Serogroup A
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_D versus MenACWY study groups, on the Meningitis serogroup A, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_D Group v MenACWY Group
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 [31]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    3.92
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 3.15
         upper limit
    		 4.88
    Notes
    [31] - Serogroup A-Between group ratio for comparison of rMenBOMV+ACWY_D group and MenACWY group.
    Statistical analysis title
    		 Immune response effects-Sergroup C
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_D versus MenACWY study groups, on the Meningitis serogroup C, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_D Group v MenACWY Group
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 [32]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    4.19
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 3.3
         upper limit
    		 5.34
    Notes
    [32] - Serogroup C- Between group ratio for comparison of rMenBOMV+ACWY_D group and MenACWY group.
    Statistical analysis title
    		 Immune response effects-Serogroup W
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_D versus MenACWY study groups, on the Meningitis serogroup W, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_D Group v MenACWY Group
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 [33]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    3.17
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 2.6
         upper limit
    		 3.87
    Notes
    [33] - Serogroup W- Between group ratio for comparison of rMenBOMV+ACWY_D group and MenACWY group.
    Statistical analysis title
    		 Immune response effects-Serogroup Y
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_D versus MenACWY study groups, on the Meningitis serogroup Y, one month after last vaccination.
    Comparison groups
    rMenBOMV+ACWY_D Group v MenACWY Group
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 [34]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    2.22
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 1.68
         upper limit
    		 2.92
    Notes
    [34] - Serogroup Y- Between group ratio for comparison of rMenBOMV+ACWY_D group and MenACWY group.
    Statistical analysis title
    		 Immune response effects-M14459 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to MenABCWY versus rMenBOMV study groups, on the Meningitis B M14459 (fHbp) strain, one month after last vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV Group
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    		 [35]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.05
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.25
    Notes
    [35] - M14459- Between group ratios for comparison of MenABCWY group and rMenBOMV group
    Statistical analysis title
    		 Immune response effects-96217 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to MenABCWY versus rMenBOMV study groups, on the Meningitis B 96217 (NadA) strain, one month after last vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV Group
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    		 [36]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.71
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 0.86
    Notes
    [36] - 96217 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV group.
    Statistical analysis title
    		 Immune response effects-NZ98/254 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to MenABCWY versus rMenBOMV study groups, on the Meningitis B NZ98/254 (PorA) strain, one month after last vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV Group
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    		 [37]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.62
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 0.76
    Notes
    [37] - NZ98/254 strain-Between group ratios for comparison of MenABCWY group and rMenBOMV group
    Statistical analysis title
    		 Immune response effects-M07-0241084 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to MenABCWY versus rMenBOMV study groups, on the Meningitis B M07-0241084 (NHBA) strain, one month after last vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV Group
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    		 [38]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.52
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 0.63
    Notes
    [38] - M07-0241084 strain-Between group ratios for comparison of MenABCWY group and rMenBOMV group
    Statistical analysis title
    		 Immune response effects-Serogroup A
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to MenABCWY versus MenACWY study groups, on the Meningitis serogroup A, one month after last vaccination.
    Comparison groups
    MenABCWY Group v MenACWY Group
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 [39]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    2.02
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 1.62
         upper limit
    		 2.51
    Notes
    [39] - Serogroup A- Between group ratios for comparison between MenABCWY group and MenACWY group
    Statistical analysis title
    		 Immune response effects-Serogroup C
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to MenABCWY versus MenACWY study groups, on the Meningitis serogroup C, one month after last vaccination.
    Comparison groups
    MenABCWY Group v MenACWY Group
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 [40]
    Method
    		 ANCOVA
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    4.99
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 3.92
         upper limit
    		 6.35
    Notes
    [40] - Serogroup C- Between group ratios for comparison of MenABCWY group and MenACWY group
    Statistical analysis title
    		 Immune response effects-Serogroup W
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to MenABCWY versus MenACWY study groups, on the Meningitis serogroup W, one month after last vaccination.
    Comparison groups
    MenABCWY Group v MenACWY Group
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 [41]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    3.25
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 2.66
         upper limit
    		 3.96
    Notes
    [41] - Serogroup W- Between group ratios for comparison of MenABCWY group and MenACWY group
    Statistical analysis title
    		 Immune response effects-Serogroup Y
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to MenABCWY versus MenACWY study groups, on the Meningitis serogroup Y, one month after last vaccination.
    Comparison groups
    MenABCWY Group v MenACWY Group
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 [42]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    2.38
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 1.81
         upper limit
    		 3.12
    Notes
    [42] - Serogroup Y- Between group ratio for comparison of MenABCWY group and MenACWY group

    Primary: Percentage of subjects with hSBA titers greater than or equal to(≥) the Lower Limit Of Quantitation (LLOQ) against each of the N. meningitidis serogroup B test strains and serogroups A, C, W-135 and Y,one month after last vaccination.

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    End point title
    		 Percentage of subjects with hSBA titers greater than or equal to(≥) the Lower Limit Of Quantitation (LLOQ) against each of the N. meningitidis serogroup B test strains and serogroups A, C, W-135 and Y,one month after last vaccination. [43]
    End point description
    Immune responses against N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, were calculated in terms of percentage of subjects with hSBA titers ≥ LLOQ. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). Analysis was performed on PPS for immunogenicity that included subjects who had no major protocol violations and whose assay results were available for at least 1 serogroup or B strain at Day 91 for all study groups except MenACWY Group or at Day 31 for the MenACWY Group.
    End point type
    Primary
    End point timeframe
    1 month after last vaccination i.e.: at Day 91 for all groups except the MenACWY Group, and at Day 31 for the MenACWY Group.
    Notes
    [43] - 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: Aim of this endpoint was descriptive analysis. No statistical analyses were performed.
    End point values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group MenACWY Group
    Number of subjects analysed
    98
    101
    97
    90
    97
    Units: Percentage of subjects
    number (confidence interval 80%)
        M14459 (fHbp)(N-97,100,96,90,97)
    83.5 (77.64 to 88.28)
    86.0 (80.50 to 90.35)
    88.5 (83.22 to 92.57)
    83.3 (77.18 to 88.31)
    12.4 (8.21 to 17.78)
        96217(NadA)(N-98,100,97,90,96)
    96.9 (93.31 to 98.87)
    99.0 (96.17 to 99.89)
    99.0 (96.05 to 99.89)
    100.0 (97.47 to 100.00)
    33.3 (26.96 to 40.24)
        NZ98/254 (PorA)(N-98,100,97,89,97)
    59.2 (52.22 to 65.86)
    76.0 (69.66 to 81.53)
    80.4 (74.27 to 85.57)
    78.7 (72.05 to 84.23)
    5.2 (2.53 to 9.35)
        M07-0241084 (NHBA)(N-98,100,96,89,95)
    59.2 (52.22 to 65.86)
    74.0 (67.54 to 79.71)
    77.1 (70.66 to 82.62)
    80.9 (74.48 to 86.22)
    23.2 (17.57 to 29.64)
        Meningitis A(N-97,101,97,90,93)
    94.8 (90.65 to 97.47)
    100.0 (97.75 to 100.00)
    99.0 (96.05 to 99.89)
    91.1 (85.96 to 94.76)
    68.8 (61.86 to 75.15)
        Meningitis C(N-98,100,97,90,97)
    100.0 (97.68 to 100.00)
    100.0 (97.72 to 100.00)
    100.0 (97.65 to 100.00)
    96.7 (92.73 to 98.77)
    86.6 (81.06 to 90.92)
        Meningitis W(N-98,100,96,90,97)
    98.0 (94.66 to 99.46)
    96.0 (92.17 to 98.24)
    99.0 (96.01 to 99.89)
    93.3 (88.59 to 96.46)
    66.0 (59.09 to 72.36)
        Menngitis Y(N-97,100,97,89,96)
    99.0 (96.05 to 99.89)
    98.0 (94.77 to 99.47)
    96.9 (93.24 to 98.86)
    24.7 (18.79 to 31.54)
    85.4 (79.71 to 89.94)
    No statistical analyses for this end point

    Primary: Percentage of subjects with a 4-fold increase in hSBA titers against each of the N. meningitidis serogroup B test strains and against N. meningitidis serogroups A, C, W-135 and Y, one month after last vaccination.

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    End point title
    		 Percentage of subjects with a 4-fold increase in hSBA titers against each of the N. meningitidis serogroup B test strains and against N. meningitidis serogroups A, C, W-135 and Y, one month after last vaccination. [44]
    End point description
    Immune responses against N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, were calculated in terms of percentage of subjects with a 4-fold increase in hSBA titers. A 4-fold rise was defined as: a) for individuals whose pre-vaccination titers were less than (<) the limit of detection (LOD), the post-vaccination titers must have been ≥4-fold the LOD or ≥ the LLOQ, whichever was greater; b) for individuals whose pre-vaccination titers were ≥ the LOD and less than (<) the LLOQ, the post-vaccination titers must have been at least 4 times the LLOQ; and c) for individuals whose pre-vaccination titers were ≥ the LLOQ, the post-vaccination titers must have been at least 4 times the pre-vaccination titer. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA).
    End point type
    Primary
    End point timeframe
    1 month after last vaccination versus baseline (i.e.: at Day 91 versus Day 1 for all groups except the MenACWY Group, and at Day 31 versus Day 1 for the MenACWY Group).
    Notes
    [44] - 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: Aim of this endpoint was descriptive analysis. No statistical analyses were performed.
    End point values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group MenACWY Group
    Number of subjects analysed
    98
    100
    97
    90
    97
    Units: Percentage of subjects
    number (confidence interval 80%)
        M14459 (fHbp)(N-97,100,95,90,97)
    66.0 (59.09 to 72.36)
    69.0 (62.32 to 75.09)
    66.3 (59.36 to 72.74)
    63.3 (56.09 to 70.11)
    2.1 (0.55 to 5.39)
        96217(NadA)(N-97,100,95,88,96)
    80.4 (74.27 to 85.57)
    88.0 (82.74 to 92.04)
    90.5 (85.46 to 94.20)
    80.7 (74.20 to 86.06)
    2.1 (0.56 to 5.45)
        NZ98/254 (PorA)(N-98,100,97,89,97)
    48.0 (41.06 to 54.92)
    60.0 (53.11 to 66.58)
    58.8 (51.75 to 65.49)
    60.7 (53.35 to 67.63)
    1.0 (0.11 to 3.95)
        M07-0241084(NHBA)(N-98,98,95,87,94)
    21.4 (16.10 to 27.68)
    38.8 (32.18 to 45.72)
    42.1 (35.27 to 49.20)
    56.3 (48.88 to 63.54)
    2.1 (0.57 to 5.56)
        Meningitis A(96,100,95,90,92)
    92.7 (88.04 to 95.90)
    99.0 (96.17 to 99.89)
    98.9 (95.97 to 99.89)
    87.8 (82.14 to 92.06)
    67.4 (60.34 to 73.85)
        Meningitis C(N-98,99,97,89,96)
    90.8 (85.89 to 94.38)
    91.9 (87.21 to 95.24)
    86.6 (81.06 to 90.92)
    57.3 (49.95 to 64.40)
    52.1 (45.05 to 59.05)
        Meningitis W(N-96,98,93,85,95)
    83.3 (77.41 to 88.15)
    78.6 (72.32 to 83.90)
    74.2 (67.48 to 80.10)
    74.1 (67.04 to 80.30)
    41.1 (34.26 to 48.14)
        Meningitis Y(N-97,99,95,88,95)
    95.9 (91.93 to 98.19)
    91.9 (87.21 to 95.24)
    93.7 (89.18 to 96.65)
    11.4 (7.19 to 16.97)
    76.8 (70.36 to 82.43)
    No statistical analyses for this end point

    Primary: hSBA Adjusted Geometric Mean Ratios (GMRs) against each of the N. meningitidis serogroup B test strains and against N. meningitidis serogroups A, C, W-135 and Y, one month after last vaccination.

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    End point title
    		 hSBA Adjusted Geometric Mean Ratios (GMRs) against each of the N. meningitidis serogroup B test strains and against N. meningitidis serogroups A, C, W-135 and Y, one month after last vaccination. [45]
    End point description
    hSBA mean ratios at 1 month after the last vaccination versus baseline were calculated in terms of GMRs i.e. as the anti-logarithm of the mean of the change from baseline of log-transformed titer values at 1 month after last vaccination and Baseline. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). Adjusted means were obtained from ANCOVA model fitted to each Serogroup (Strain) individually, study group and center as fixed effects and zero-centered pre-vaccination log-transformed titer as a continuous covariate. Analysis was performed on PPS for immunogenicity that included subjects who had no major protocol violations and whose assay results were available for at least 1 serogroup or B strain at Day 91 for all study groups except MenACWY Group or at Day 31 for the MenACWY Group and at baseline for all study groups.
    End point type
    Primary
    End point timeframe
    1 month after last vaccination versus baseline (i.e.: at Day 91 versus Day 1 for all groups except the MenACWY Group, and at Day 31 versus Day 1 for the MenACWY Group).
    Notes
    [45] - 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: Aim of this endpoint was descriptive analysis. No statistical analyses were performed.
    End point values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group MenACWY Group
    Number of subjects analysed
    98
    100
    97
    90
    97
    Units: Ratio
    geometric mean (confidence interval 80%)
        M14459(N-97,100,95,90,97)
    11.17 (9.59 to 13.02)
    10.90 (9.42 to 12.62)
    10.85 (9.30 to 12.66)
    10.69 (9.12 to 12.52)
    1.16 (0.99 to 1.35)
        96217(N-97,100,95,88,96)
    21.33 (18.22 to 24.99)
    27.02 (23.22 to 31.44)
    25.66 (21.88 to 30.10)
    29.87 (25.32 to 35.24)
    1.09 (0.93 to 1.28)
        NZ98/254(N-98,100,97,89,97)
    7.28 (6.11 to 8.67)
    9.20 (7.78 to 10.88)
    11.85 (9.94 to 14.13)
    11.77 (9.81 to 14.12)
    1.21 (1.01 to 1.44)
        M07-0241084(NHBA)(N-98,98,95,87,94)
    3.60 (3.05 to 4.25)
    4.96 (4.23 to 5.81)
    6.22 (5.27 to 7.35)
    6.98 (5.87 to 8.30)
    1.12 (0.95 to 1.33)
        Meningitis A(N-96,100,95,90,92)
    33.21 (27.55 to 40.04)
    59.36 (49.68 to 70.93)
    64.58 (53.52 to 77.93)
    30.05 (24.77 to 36.44)
    16.47 (13.62 to 19.93)
        Meningitis C(N-98,99,97,89,96)
    34.34 (27.88 to 42.30)
    28.74 (23.52 to 35.13)
    28.86 (23.40 to 35.60)
    6.35 (5.11 to 7.90)
    6.88 (5.58 to 8.49)
        Meningitis W(N-96,98,93,85,95)
    24.58 (20.72 to 29.15)
    23.21 (19.69 to 27.36)
    24.02 (20.20 to 28.56)
    18.29 (15.28 to 21.90)
    7.57 (6.37 to 8.99)
        Meningitis Y(N-97,99,95,88,95)
    106.87 (84.27 to 135.53)
    90.59 (72.18 to 113.70)
    99.76 (78.58 to 126.66)
    1.78 (1.39 to 2.28)
    44.99 (35.42 to 57.14)
    No statistical analyses for this end point

    Secondary: hSBA Adjusted GMTs against all of N. meningitidis serogroup B test strains (pooled), one month after first vaccination

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    End point title
    		 hSBA Adjusted GMTs against all of N. meningitidis serogroup B test strains (pooled), one month after first vaccination [46]
    End point description
    hSBA titers against all of N. meningitidis serogroup B test strains were calculated in terms of GMTs. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). The serogroup B strains were grouped together to perform a pooled analysis. Adjusted means were obtained from ANCOVA model fitted to all of the Serogroup B test strains, study group, test strain and center as fixed effects; zero-centered pre-vaccination log-transformed titer was included as a continuous covariate. Analysis was performed on PPS for immunogenicity that included subjects who had no major protocol violations and whose assay results were available for at least 1 serogroup or B strain after first vaccination for all study groups except for MenACWY group that was not considered for this analysis as only serogroup B strains assessed in this outcome.
    End point type
    Secondary
    End point timeframe
    1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group
    Notes
    [46] - 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: MenACWY group was not considered for this analysis as only serogroup B strains were assessed in this outcome measure.
    End point values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group
    Number of subjects analysed
    96
    103
    98
    91
    Units: Titers
        geometric mean (confidence interval 80%)
    6.51 (5.63 to 7.52)
    8.33 (7.24 to 9.58)
    8.16 (7.08 to 9.41)
    9.45 (8.14 to 10.95)
    Statistical analysis title
    		 Immune interference- Pooled B strains
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the pooled B strains, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    201
    Analysis specification
    Pre-specified
    Analysis type
    		 [47]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.02
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.22
    Notes
    [47] - Between group ratio is calculated as GMT for rMenBOMV+ACWY_S Group over GMT for rMenBOMV+ACWY_D Group. 80% CI are obtained from Analysis of Covariance model fitted to pooled Serogroup B Strains. The following ANCOVA model is used: fixed-effect model including age strata, study group, strain and center as fixed effects. The pre vaccination (Baseline) log-transformed titer with centering at zero is included as a continuous covariate.

    Secondary: hSBA Adjusted GMTs against each of the N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135 and Y, one month after first vaccination.

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    End point title
    		 hSBA Adjusted GMTs against each of the N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135 and Y, one month after first vaccination. [48]
    End point description
    hSBA titers against each of the N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y were calculated in terms of GMTs. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). Adjusted means were obtained from ANCOVA model fitted to each Serogroup (Strain) individually, study group and center as fixed effects and zero-centered pre-vaccination log-transformed titer as a continuous covariate. Analysis was performed on PPS for immunogenicity that included subjects who had no major protocol violations and whose assay results were available for at least 1 serogroup or B strain after first vaccination for all study groups except for MenACWY Group for which results were included in the last vaccination analysis (see primary outcome measure 2).
    End point type
    Secondary
    End point timeframe
    1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group.
    Notes
    [48] - 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: MenACWY group was not considered for this analysis as only serogroup B strains were assessed in this outcome measure.
    End point values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group
    Number of subjects analysed
    96
    103
    98
    91
    Units: Titers
    geometric mean (confidence interval 80%)
        M14459 (N-95,103,98,90)
    5.50 (4.55 to 6.66)
    6.36 (5.29 to 7.65)
    4.94 (4.09 to 5.96)
    6.08 (5.00 to 7.39)
        96217
    8.21 (6.87 to 9.81)
    11.30 (9.51 to 13.42)
    12.18 (10.23 to 14.52)
    14.07 (11.72 to 16.89)
        NZ98/254 (N-96,103,98,90)
    3.79 (3.10 to 4.63)
    4.83 (3.98 to 5.86)
    4.76 (3.91 to 5.79)
    5.48 (4.47 to 6.71)
        M07-0241084(N-94,101,96,90)
    6.27 (5.23 to 7.52)
    7.31 (6.12 to 8.73)
    6.75 (5.65 to 8.06)
    7.69 (6.38 to 9.26)
        Meningitis A(N-95,102,96,90)
    31.38 (24.79 to 39.73)
    67.95 (54.07 to 85.40)
    88.29 (69.95 to 111.44)
    8.22 (6.48 to 10.44)
        Meningitis C(N-96,102,97,90)
    41.35 (32.39 to 52.79)
    33.76 (26.61 to 42.85)
    40.33 (31.71 to 51.29)
    11.47 (8.92 to 14.74)
        Meningitis W(N-96,102,97,88)
    108.91 (88.67 to 133.78)
    81.38 (66.62 to 99.42)
    92.84 (75.75 to 113.80)
    42.99 (34.66 to 53.33)
        Meningitis Y(N-95,99,95,90)
    75.07 (56.86 to 99.13)
    76.48 (58.31 to 100.32)
    100.30 (76.13 to 132.15)
    3.98 (3.00 to 5.30)
    Statistical analysis title
    		 Immune interference-M14459 strain
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis B M14459 (fHbp) strain, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    201
    Analysis specification
    Pre-specified
    Analysis type
    		 [49]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.29
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 1.02
         upper limit
    		 1.63
    Notes
    [49] - M14459 strain- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group.
    Statistical analysis title
    		 Immune interference-96217 strain
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis B 96217 (NadA) strain, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    201
    Analysis specification
    Pre-specified
    Analysis type
    		 [50]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.93
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.15
    Notes
    [50] - 96217 strain- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group.
    Statistical analysis title
    		 Immune interference-NZ98/254 strain
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis B NZ98/254 (PorA)strain, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    201
    Analysis specification
    Pre-specified
    Analysis type
    		 [51]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.01
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 1.29
    Notes
    [51] - NZ98/254 strain- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group.
    Statistical analysis title
    		 Immune interference-M07-0241084 strain
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis B M07-0241084 (NHBA) strain, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    201
    Analysis specification
    Pre-specified
    Analysis type
    		 [52]
    Method
    		 ANCOVA
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.08
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.36
    Notes
    [52] - M07-0241084 strain-Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group.
    Statistical analysis title
    		 Immune interference-Serogroup A
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis serogroup A, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    201
    Analysis specification
    Pre-specified
    Analysis type
    		 [53]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.77
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 1.03
    Notes
    [53] - Serogroup A- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group.
    Statistical analysis title
    		 Immune interference-Serogroup C
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis serogroup C, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    201
    Analysis specification
    Pre-specified
    Analysis type
    		 [54]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.84
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 1.13
    Notes
    [54] - Serogroup C- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D Group.
    Statistical analysis title
    		 Immune interference-Serogroup W
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis serogroup W, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    201
    Analysis specification
    Pre-specified
    Analysis type
    		 [55]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.88
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 1.13
    Notes
    [55] - Serogroup W- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group.
    Statistical analysis title
    		 Immune interference-Serogroup Y
    Statistical analysis description
    Immune interference due to stress to lymph nodes (lymph-node effect) in rMenBOMV+ACWY_S versus rMenBOMV+ACWY_D study groups, on the Meningitis serogroup Y, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV+ACWY_D Group
    Number of subjects included in analysis
    201
    Analysis specification
    Pre-specified
    Analysis type
    		 [56]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.76
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.08
    Notes
    [56] - Serogroup Y- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group.
    Statistical analysis title
    		 Other unknown interference-M14459 strain
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B M14459 (fHbp) strain, one month after first vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [57]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.87
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.09
    Notes
    [57] - M14459 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Other unknown interference-96217 strain
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B 96217 (NadA) strain, one month after first vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [58]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.73
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 0.9
    Notes
    [58] - 96217 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Other unknown interference-NZ98/254 strain
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B NZ98/254 (PorA) strain, one month after first vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [59]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.78
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 1
    Notes
    [59] - NZ98/254 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Other unknown interference-M07-0241084
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B M07-0241084 (NHBA) strain, one month after first vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [60]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.86
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 1.07
    Notes
    [60] - M07-0241084 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Other unknown interference-Serogroup A
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogroup A, one month after first vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [61]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.46
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.35
         upper limit
    		 0.62
    Notes
    [61] - Serogroup A- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Other unknown interference-Serogroup C
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogroup C, one month after first vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [62]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.22
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.65
    Notes
    [62] - Serogroup C- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Other unknown interference-Serogroup W
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogroup W, one month after first vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [63]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.34
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 1.04
         upper limit
    		 1.72
    Notes
    [63] - Serogroup W- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Other unknown interference-Serogroup Y
    Statistical analysis description
    Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogroup Y, one month after first vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV+ACWY_S Group
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 [64]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.98
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.38
    Notes
    [64] - Serogroup Y- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
    Statistical analysis title
    		 Immune response effects-M14459 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_S versus rMenBOMV study groups, on the Meningitis B M14459 (fHbp) strain, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV Group
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 [65]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.05
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.32
    Notes
    [65] - M14459 strain-Between group ratio for comparison of rMenBOMV_ACWY_S group and rMenBOMV group.
    Statistical analysis title
    		 Immune response effects-96217 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_S versus rMenBOMV study groups, on the Meningitis B 96217 (NadA) strain, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV Group
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 [66]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.8
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 1
    Notes
    [66] - 96217 strain-Between group ratio for comparison of rMenBOMV_ACWY_S group and rMenBOMV group
    Statistical analysis title
    		 Immune response effects-NZ98/254 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_S versus rMenBOMV study groups, on the Meningitis B NZ98/254 (PorA) strain, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV Group
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 [67]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.88
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.13
    Notes
    [67] - NZ98/254 strain -Between group ratio for comparison of rMenBOMV_ACWY_S group and rMenBOMV group
    Statistical analysis title
    		 Immune response effects-M07-0241084
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_S versus rMenBOMV study groups, on the Meningitis B M07-0241084 (NHBA) strain, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_S Group v rMenBOMV Group
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 [68]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.95
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.19
    Notes
    [68] - M07-0241084 strain -Between group ratio for comparison of rMenBOMV_ACWY_S group and rMenBOMV group
    Statistical analysis title
    		 Immune response effects- M14459 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_D versus rMenBOMV study groups, on the Meningitis B M14459 (fHbp) strain, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_D Group v rMenBOMV Group
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 [69]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.81
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 1.03
    Notes
    [69] - M14459 strain -Between group ratio for comparison of rMenBOMV_ACWY_D group and rMenBOMV group
    Statistical analysis title
    		 Immune response effects- 96217 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_D versus rMenBOMV study groups, on the Meningitis B 96217 (NadA) strain, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_D Group v rMenBOMV Group
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 [70]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.87
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.09
    Notes
    [70] - 96217 strain -Between group ratio for comparison of rMenBOMV_ACWY_D group and rMenBOMV group
    Statistical analysis title
    		 Immune response effects-NZ98/254 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_D versus rMenBOMV study groups, on the Meningitis B NZ98/254 (PorA) strain, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_D Group v rMenBOMV Group
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 [71]
    Method
    		 ANCOVA
    Parameter type
    		 Geometrical mean ratio
    Point estimate
    0.87
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 1.12
    Notes
    [71] - NZ98/254 strain -Between group ratio for comparison of rMenBOMV_ACWY_D group and rMenBOMV group
    Statistical analysis title
    		 Immune response effects-M07-0241084
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to rMenBOMV+ACWY_D versus rMenBOMV study groups, on the Meningitis B M07-0241084 (NHBA) strain, one month after first vaccination.
    Comparison groups
    rMenBOMV+ACWY_D Group v rMenBOMV Group
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 [72]
    Method
    		 ANCOVA
    Parameter type
    		 Geometrical mean ratio
    Point estimate
    0.88
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.1
    Notes
    [72] - M07-0241084 strain-Between group ratio for comparison of rMenBOMV_ACWY_D group and rMenBOMV group
    Statistical analysis title
    		 Immune response effects-M14459 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to MenABCWY versus rMenBOMV study groups, on the Meningitis B M14459 (fHbp)strain, one month after first vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV Group
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 [73]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.91
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.15
    Notes
    [73] - M14459 strain-Between group ratio for comparison of MenABCWY group and rMenBOMV group
    Statistical analysis title
    		 Immune response effects-96217 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to MenABCWY versus rMenBOMV study groups, on the Meningitis B 96217 (NadA) strain, one month after first vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV Group
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 [74]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.58
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 0.73
    Notes
    [74] - 96217 strain-Between group ratio for comparison of MenABCWY group and rMenBOMV group
    Statistical analysis title
    		 Immune response effects-NZ98/254 strain
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to MenABCWY versus rMenBOMV study groups, on the Meningitis B NZ98/254 (PorA) strain, one month after first vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV Group
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 [75]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.69
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 0.89
    Notes
    [75] - NZ98/254 strain-Between group ratio for comparison of MenABCWY group and rMenBOMV group
    Statistical analysis title
    		 Immune response effects-M07-0241084
    Statistical analysis description
    To investigate possible effects on the immune response based on strains common to MenABCWY versus rMenBOMV study groups, on the Meningitis B M07-0241084 (NHBA) strain, one month after first vaccination.
    Comparison groups
    MenABCWY Group v rMenBOMV Group
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 [76]
    Method
    		 ANCOVA
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.82
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 1.03
    Notes
    [76] - M07-0241084 strain-Between group ratio for comparison of MenABCWY group and rMenBOMV group

    Secondary: Percentage of subjects with hSBA titers greater than or equal to (≥) the LLOQ against each of the N. meningitidis serogroup B test strains and against serogroups A, C, W-135, and Y, one month after first vaccination

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    End point title
    		 Percentage of subjects with hSBA titers greater than or equal to (≥) the LLOQ against each of the N. meningitidis serogroup B test strains and against serogroups A, C, W-135, and Y, one month after first vaccination [77]
    End point description
    Immune responses against N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, were calculated in terms of percentage of subjects with hSBA titers ≥ LLOQ. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). Analysis was performed on PPS for immunogenicity that included subjects who had no major protocol violations and whose assay results were available for at least 1 serogroup or B strain after first vaccination for all study groups except for MenACWY Group for which results were included in the last vaccination analysis (see primary outcome measure 3).
    End point type
    Secondary
    End point timeframe
    1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group
    Notes
    [77] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: MenACWY group was not considered for this analysis as only serogroup B strains were assessed in this outcome measure.
    End point values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group
    Number of subjects analysed
    96
    103
    98
    91
    Units: Percentage of subjects
    number (confidence interval 80%)
        M14459 (fHbp)(N-95,103,98,90)
    36.8 (30.24 to 43.88)
    49.5 (42.77 to 56.27)
    37.8 (31.21 to 44.69)
    42.2 (35.19 to 49.53)
        96217 (NadA)
    57.3 (50.24 to 64.11)
    66.0 (59.35 to 72.20)
    69.4 (62.65 to 75.51)
    75.8 (69.12 to 81.64)
        NZ98/254 (PorA)(N-96,103,98,90)
    29.2 (23.08 to 35.93)
    37.9 (31.48 to 44.61)
    33.7 (27.35 to 40.51)
    37.8 (30.94 to 45.04)
        M07-0241084 (NHBA)(N-94,101,96,90)
    35.1 (28.56 to 42.14)
    49.5 (42.69 to 56.33)
    37.5 (30.90 to 44.51)
    44.4 (37.33 to 51.75)
        Meningitis A(N-95,102,97,90)
    65.3 (58.28 to 71.75)
    73.5 (67.12 to 79.22)
    80.2 (74.01 to 85.41)
    25.6 (19.58 to 32.38)
        Meningitis C(N-96,102,97,90)
    89.6 (84.41 to 93.42)
    94.1 (89.90 to 96.88)
    92.8 (88.16 to 95.94)
    70.0 (62.96 to 76.35)
        Meningitis W(N-96,102,97,88)
    71.9 (65.16 to 77.88)
    70.6 (64.04 to 76.51)
    74.2 (67.67 to 80.00)
    52.3 (44.90 to 59.56)
        Meningitis Y(N-95,99,95,90)
    83.2 (77.18 to 88.02)
    81.8 (75.86 to 86.76)
    88.4 (83.05 to 92.49)
    20.0 (14.60 to 26.45)
    No statistical analyses for this end point

    Secondary: Percentage of subjects with a 4-fold increase in hSBA titers against each of the N. meningitidis serogroup B test strains and against N. meningitidis serogroups A, C, W-135, and Y, one month after first vaccination

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    End point title
    		 Percentage of subjects with a 4-fold increase in hSBA titers against each of the N. meningitidis serogroup B test strains and against N. meningitidis serogroups A, C, W-135, and Y, one month after first vaccination [78]
    End point description
    Immune responses against N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, were calculated in terms of percentage of subjects with a 4-fold increase in hSBA titers. A 4-fold rise is defined as: a) for individuals whose pre-vaccination titers were less than (<) the limit of detection (LOD), the post-vaccination titers must have been ≥4-fold the LOD or ≥ the LLOQ, whichever was greater; b) for individuals whose pre-vaccination titers were ≥ the LOD and less than (<) the LLOQ, the post-vaccination titers must have been at least 4 times the LLOQ; and c) for individuals whose pre-vaccination titers were ≥ the LLOQ, the post-vaccination titers must have been at least 4 times the pre-vaccination titer. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA).
    End point type
    Secondary
    End point timeframe
    1 month after first vaccination versus baseline (i.e.: at Day 31 versus Day 1 for all groups except for the MenACWY Group)
    Notes
    [78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: MenACWY group was not considered for this analysis as only serogroup B strains were assessed in this outcome measure.
    End point values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group
    Number of subjects analysed
    96
    103
    97
    91
    Units: Percentage of subjects
    number (confidence interval 80%)
        M14459 (fHbp)(N-95,103,96,90)
    24.2 (18.52 to 30.76)
    24.3 (18.80 to 30.53)
    18.8 (13.67 to 24.86)
    25.6 (19.58 to 32.38)
        96217 (NadA)(N-95,103,95,89)
    22.1 (16.62 to 28.51)
    34.0 (27.80 to 40.65)
    30.5 (24.31 to 37.38)
    32.6 (26.01 to 39.77)
        NZ98/254 (PorA)(N-96,103,97,90)
    20.8 (15.51 to 27.11)
    26.2 (20.57 to 32.58)
    26.8 (20.94 to 33.42)
    27.8 (21.60 to 34.72)
        M07-0241084 (NHBA)(N-94,97,94,88)
    9.6 (5.86 to 14.69)
    20.6 (15.35 to 26.84)
    13.8 (9.37 to 19.52)
    20.5 (14.94 to 27.03)
        Meningitis A(N-94,101,93,90)
    61.7 (54.60 to 68.42)
    71.3 (64.73 to 77.18)
    80.6 (74.37 to 85.88)
    23.3 (17.57 to 30.03)
        Meningitis C(N-96,101,96,89)
    54.2 (47.11 to 61.09)
    46.5 (39.78 to 53.39)
    51.0 (44.02 to 58.03)
    24.7 (18.79 to 31.54)
        Meningitis W(N-94,100,93,83)
    60.6 (53.53 to 67.40)
    52.0 (45.12 to 58.82)
    51.6 (44.46 to 58.71)
    39.8 (32.53 to 47.37)
        Meningitis Y(N-95,98,92,89)
    77.9 (71.49 to 83.38)
    75.5 (69.06 to 81.14)
    78.3 (71.76 to 83.79)
    9.0 (5.30 to 14.19)
    No statistical analyses for this end point

    Secondary: hSBA Adjusted GMRs against each of the N. meningitidis serogroup B test strains and against N. meningitidis serogroups A, C, W-135, and Y, one month after first vaccination

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    End point title
    		 hSBA Adjusted GMRs against each of the N. meningitidis serogroup B test strains and against N. meningitidis serogroups A, C, W-135, and Y, one month after first vaccination [79]
    End point description
    hSBA mean ratios at 1 month after the first vaccination versus baseline were calculated in terms of GMRs i.e. as the anti-logarithm of the mean of the change from baseline of log-transformed titer values at 1 month after last vaccination and Baseline. Serogroup B strains tested were M14459 (factor H binding protein; fHbp),96217 (Neisserial adhesin A; NadA),NZ98/254 (PorA) and M070241084 (Neisseria heparin binding antigen; NHBA).Adjusted mean was obtained from ANCOVA model fitted to each Serogroup (Strain) individually,study group and center as fixed effects and zero-centered pre-vaccination log-transformed titer as a continuous covariate.Analysis was performed on PPS for immunogenicity that included subjects who had no major protocol violations and whose assay results were available for at least 1 serogroup or B strain after first vaccination for all study groups except for MenACWY Group for which results were included in the last vaccination analysis (see primary outcome measure 5)
    End point type
    Secondary
    End point timeframe
    1 month after first vaccination versus baseline (i.e.: at Day 31 versus Day 1 for all groups except for the MenACWY Group)
    Notes
    [79] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: MenACWY group was not considered for this analysis as only serogroup B strains were assessed in this outcome measure.
    End point values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group
    Number of subjects analysed
    96
    103
    97
    90
    Units: Ratio
    geometric mean (confidence interval 80%)
        M14459 (N-95,103,96,90)
    2.59 (2.14 to 3.14)
    3.00 (2.49 to 3.61)
    2.33 (1.93 to 2.81)
    2.87 (2.36 to 3.48)
        96217(N-95,103,95,89)
    2.15 (1.80 to 2.57)
    2.96 (2.49 to 3.51)
    3.19 (2.68 to 3.80)
    3.68 (3.07 to 4.42)
        NZ98/254 (N-96,103,97,90)
    2.16 (1.77 to 2.64)
    2.76 (2.27 to 3.34)
    2.72 (2.23 to 3.31)
    3.13 (2.55 to 3.83)
        M07-0241084 (N-94,97,94,88)
    1.73 (1.44 to 2.07)
    2.01 (1.69 to 2.41)
    1.86 (1.56 to 2.22)
    2.12 (1.76 to 2.55)
        Meningitis A(N-94,101,93,90)
    10.15 (8.02 to 12.85)
    21.97 (17.48 to 27.62)
    28.55 (22.62 to 36.04)
    2.66 (2.09 to 3.38)
        Meningitis C(N-96,101,96,89)
    8.08 (6.33 to 10.31)
    6.59 (5.20 to 8.37)
    7.88 (6.19 to 10.02)
    2.24 (1.74 to 2.88)
        Meningitis W(N-94,100,93,83)
    11.08 (9.02 to 13.60)
    8.28 (6.77 to 10.11)
    9.44 (7.70 to 11.57)
    4.37 (3.52 to 5.42)
        Meningitis Y(N-95,98,92,89)
    36.58 (27.70 to 48.30)
    37.26 (28.41 to 48.88)
    48.87 (37.09 to 64.39)
    1.94 (1.46 to 2.58)
    No statistical analyses for this end point

    Secondary: Number of subjects with any solicited local Adverse Events (AEs)

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    End point title
    		 Number of subjects with any solicited local Adverse Events (AEs)
    End point description
    Assessed local AEs were erythema, swelling, induration and pain. Any erythema, swelling and induration is defined as a symptom with a surface diameter equal to or greater than 25 millimeters.Analysis was performed on the solicited safety set that included all subjects who provided informed consent, underwent screening procedures, had a subject number assigned, received a study vaccination and was reported with any solicited adverse event data. No results for dose 2 categories for subjects of MenACWY Group as they received only 1 dose at day 1.
    End point type
    Secondary
    End point timeframe
    During the 7 days (including the day of vaccination) after each vaccination i.e after Dose 1 administered at Day 1 (for all groups) and after Dose 2 administered at Day 61 (for all groups except for MenACWY Group)
    End point values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group MenACWY Group
    Number of subjects analysed
    100
    104
    100
    94
    102
    Units: Participants
        Erythema at Dose 1
    17
    19
    18
    9
    7
        Swelling at Dose 1
    20
    21
    16
    13
    10
        Induration at Dose 1
    9
    15
    12
    6
    4
        Pain at Dose 1
    89
    100
    95
    88
    52
        Erythema at Dose 2
    15
    18
    15
    10
    0
        Swelling at Dose 2
    13
    14
    15
    12
    0
        Induration at Dose 2
    6
    11
    12
    12
    0
        Pain at Dose 2
    87
    97
    95
    87
    0
    No statistical analyses for this end point

    Secondary: Number of subjects with any solicited systemic AEs

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    End point title
    		 Number of subjects with any solicited systemic AEs
    End point description
    Assessed systemic AEs were arthralgia, fatigue, nausea, headache, myalgia and fever. Any fever is defined as body temperature equal or greater than 38 degrees Celsius. Analysis was performed on the solicited safety set that included all subjects who provided informed consent, underwent screening procedures, had a subject number assigned, received a study vaccination and was reported with any solicited adverse event data. No results for dose 2 category for subjects of MenACWY Group as they received only 1 dose at day 1.
    End point type
    Secondary
    End point timeframe
    During the 7 days (including the day of vaccination) after each vaccination i.e after Dose 1 administered at Day 1 (for all groups) and after Dose 2 administered at Day 61 (for all groups except for MenACWY Group)
    End point values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group MenACWY Group
    Number of subjects analysed
    100
    104
    100
    94
    102
    Units: Participants
        Arthralgia at Dose 1(N-98,100,96,86,98)
    20
    15
    9
    9
    18
        Fatigue at Dose 1(N-99,102,100,92,100)
    56
    61
    55
    46
    50
        Nausea at Dose 1(N-97,101,97,85,99)
    16
    23
    14
    13
    14
        Headache at Dose 1(98,102,98,92,99)
    40
    46
    38
    36
    36
        Myalgia at Dose 1(N-98,101,97,87,99)
    34
    29
    27
    21
    28
        Fever at Dose 1(N-100,103,100,94,101)
    6
    5
    5
    1
    3
        Arthralgia at Dose 2(N-98,103,98,92,0)
    22
    19
    12
    17
    0
        Fatigue at Dose 2(N-100,104,100,94,0)
    58
    61
    62
    56
    0
        Nausea at Dose 2(N-98,102,98,93,0)
    16
    13
    15
    17
    0
        Headache at Dose 2(N-98,104,100,93,0)
    52
    36
    37
    39
    0
        Myalgia at Dose 2(N-98,103,99,94,0)
    41
    38
    35
    38
    0
        Fever at Dose 2(N-100,104,100,94,0)
    6
    3
    3
    1
    0
    No statistical analyses for this end point

    Secondary: Number of subjects with unsolicited AEs

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    End point title
    		 Number of subjects with unsolicited AEs
    End point description
    An AE is any untoward medical occurrence in a clinical investigation subject,temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding),symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.For marketed medicinal products, this also includes failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse.An unsolicited AE is an AE that was not solicited using a Subject Diary and that was spontaneously communicated by a subjects/parent(s)/ Legally Acceptable Representative who has signed the informed consent or a solicited local or systemic adverse event that continues beyond the solicited period at day 7 after vaccination.Analysis was performed on unsolicited safety set.No results for dose 2 category for subjects of MenACWY Group as they received only 1 dose at day 1.
    End point type
    Secondary
    End point timeframe
    During the 30 days (including the day of vaccination) after each vaccination i.e after Dose 1 administered at Day 1 (for all groups) and after Dose 2 administered at Day 61 (for all groups except for MenACWY Group)
    End point values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group MenACWY Group
    Number of subjects analysed
    100
    104
    100
    94
    102
    Units: Participants
        Any unsolicited AEs- Dose 1
    16
    19
    16
    16
    15
        Any unsolicited AEs- Dose 2 (N-100,104,100,94,0)
    11
    14
    13
    10
    0
    No statistical analyses for this end point

    Secondary: Number of subjects with Serious Adverse Events (SAEs), medically attended AEs (MAEs), AEs leading to withdrawal, and Adverse events of special interest (AESIs)

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    End point title
    		 Number of subjects with Serious Adverse Events (SAEs), medically attended AEs (MAEs), AEs leading to withdrawal, and Adverse events of special interest (AESIs)
    End point description
    SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability or incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Medically attended AEs are defined as symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider. AESIs are predefined (serious or non-serious) adverse events of scientific and medical concern specific to the product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate, because such an event might warrant further investigation in order to characterize and understand it. Analysis was performed on the unsolicited safety set.
    End point type
    Secondary
    End point timeframe
    During the whole study period i.e from Day 1 to Day 91
    End point values
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group MenACWY Group
    Number of subjects analysed
    100
    104
    100
    94
    102
    Units: Participants
        SAE(s)
    0
    2
    1
    2
    0
        MAE(s)
    14
    17
    14
    13
    6
        AE(s) leading to withdrawal
    0
    0
    0
    0
    0
        AESI(s)
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Solicited Adverse Events were reported during the 7 days post-vaccination period and Unsolicited Adverse Events during the 30 Days post-vaccination period. Serious Adverse Events: were reported during the whole study period (from Day 1 up to Day 91).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedRA 20.1
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    MenABCWY Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of MenABCWY twice, 2 months apart (Day 1 and Day 61).

    Reporting group title
    rMenBOMV+ACWY_S Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) concomitantly received one dose of rMenB+OMV NZ (Bexsero) and one dose of MenACWY (Menveo) in the same arm twice, 2 months apart (Day 1 and Day 61).

    Reporting group title
    rMenBOMV+ACWY_D Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) concomitantly received one dose of rMenB+OMV NZ (Bexsero) and one dose of MenACWY (Menveo) in 2 different arms twice, 2 months apart (Day 1 and Day 61).

    Reporting group title
    rMenBOMV Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of rMenB+OMV NZ (Bexsero) twice, 2 months apart (Day 1 and Day 61).

    Reporting group title
    MenACWY Group
    Reporting group description
    		 Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of MenACWY (Menveo) once (Day 1).

    Serious adverse events
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group MenACWY Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 100 (0.00%)
    2 / 104 (1.92%)
    1 / 100 (1.00%)
    2 / 94 (2.13%)
    0 / 102 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    0 / 100 (0.00%)
    2 / 104 (1.92%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    1 / 94 (1.06%)
    0 / 102 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    1 / 94 (1.06%)
    0 / 102 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 MenABCWY Group rMenBOMV+ACWY_S Group rMenBOMV+ACWY_D Group rMenBOMV Group MenACWY Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    94 / 100 (94.00%)
    103 / 104 (99.04%)
    98 / 100 (98.00%)
    94 / 94 (100.00%)
    80 / 102 (78.43%)
    General disorders and administration site conditions
    Face oedema
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    1 / 94 (1.06%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Fatigue
         subjects affected / exposed
    70 / 100 (70.00%)
    74 / 104 (71.15%)
    72 / 100 (72.00%)
    63 / 94 (67.02%)
    50 / 102 (49.02%)
         occurrences all number
    114
    122
    117
    102
    50
    Inflammation
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Injection site pain
         subjects affected / exposed
    94 / 100 (94.00%)
    102 / 104 (98.08%)
    97 / 100 (97.00%)
    93 / 94 (98.94%)
    53 / 102 (51.96%)
         occurrences all number
    176
    197
    190
    175
    53
    Erythema
         subjects affected / exposed
    50 / 100 (50.00%)
    71 / 104 (68.27%)
    57 / 100 (57.00%)
    58 / 94 (61.70%)
    28 / 102 (27.45%)
         occurrences all number
    78
    108
    82
    81
    28
    Swelling
         subjects affected / exposed
    51 / 100 (51.00%)
    63 / 104 (60.58%)
    46 / 100 (46.00%)
    46 / 94 (48.94%)
    23 / 102 (22.55%)
         occurrences all number
    80
    98
    69
    65
    23
    Induration
         subjects affected / exposed
    44 / 100 (44.00%)
    54 / 104 (51.92%)
    49 / 100 (49.00%)
    38 / 94 (40.43%)
    19 / 102 (18.63%)
         occurrences all number
    65
    85
    72
    56
    19
    Pyrexia
         subjects affected / exposed
    12 / 100 (12.00%)
    7 / 104 (6.73%)
    8 / 100 (8.00%)
    2 / 94 (2.13%)
    3 / 102 (2.94%)
         occurrences all number
    13
    8
    8
    2
    3
    Injection site induration
         subjects affected / exposed
    2 / 100 (2.00%)
    5 / 104 (4.81%)
    1 / 100 (1.00%)
    4 / 94 (4.26%)
    0 / 102 (0.00%)
         occurrences all number
    2
    5
    1
    4
    0
    Injection site erythema
         subjects affected / exposed
    2 / 100 (2.00%)
    3 / 104 (2.88%)
    4 / 100 (4.00%)
    1 / 94 (1.06%)
    0 / 102 (0.00%)
         occurrences all number
    2
    3
    4
    1
    0
    Injection site swelling
         subjects affected / exposed
    3 / 100 (3.00%)
    2 / 104 (1.92%)
    1 / 100 (1.00%)
    1 / 94 (1.06%)
    0 / 102 (0.00%)
         occurrences all number
    4
    2
    1
    1
    0
    Vaccination site erythema
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    3 / 100 (3.00%)
    0 / 94 (0.00%)
    1 / 102 (0.98%)
         occurrences all number
    0
    0
    3
    0
    1
    Vaccination site swelling
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    2 / 100 (2.00%)
    0 / 94 (0.00%)
    2 / 102 (1.96%)
         occurrences all number
    0
    0
    2
    0
    2
    Vaccination site induration
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    1 / 102 (0.98%)
         occurrences all number
    0
    0
    1
    0
    1
    Injection site hypersensitivity
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Injection site discolouration
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Immune system disorders
    Food allergy
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    1 / 102 (0.98%)
         occurrences all number
    0
    0
    0
    0
    1
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 104 (0.96%)
    1 / 100 (1.00%)
    1 / 94 (1.06%)
    0 / 102 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Investigations
    Weight decreased
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Weight increased
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    Ligament sprain
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    2 / 94 (2.13%)
    0 / 102 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    Arthropod bite
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    1 / 94 (1.06%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Contusion
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    1 / 94 (1.06%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Foot fracture
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Head injury
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Limb injury
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Thermal burn
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Arthropod sting
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Vaccination complication
         subjects affected / exposed
    2 / 100 (2.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Nervous system disorders
    Migraine
         subjects affected / exposed
    0 / 100 (0.00%)
    2 / 104 (1.92%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Syncope
         subjects affected / exposed
    0 / 100 (0.00%)
    2 / 104 (1.92%)
    0 / 100 (0.00%)
    2 / 94 (2.13%)
    1 / 102 (0.98%)
         occurrences all number
    0
    2
    0
    2
    1
    Headache
         subjects affected / exposed
    60 / 100 (60.00%)
    57 / 104 (54.81%)
    54 / 100 (54.00%)
    52 / 94 (55.32%)
    36 / 102 (35.29%)
         occurrences all number
    92
    82
    75
    75
    36
    Dizziness
         subjects affected / exposed
    1 / 100 (1.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Gastrointestinal disorders
    Toothache
         subjects affected / exposed
    1 / 100 (1.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    2 / 94 (2.13%)
    1 / 102 (0.98%)
         occurrences all number
    1
    1
    0
    2
    1
    Abdominal pain
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Anal fissure
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Dyspepsia
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Enteritis
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Gastritis
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Nausea
         subjects affected / exposed
    24 / 100 (24.00%)
    26 / 104 (25.00%)
    26 / 100 (26.00%)
    26 / 94 (27.66%)
    14 / 102 (13.73%)
         occurrences all number
    32
    36
    29
    30
    14
    Diarrhoea
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    2 / 102 (1.96%)
         occurrences all number
    0
    1
    0
    0
    2
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    1 / 100 (1.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Eczema
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Erythema
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    1 / 94 (1.06%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 104 (0.96%)
    1 / 100 (1.00%)
    1 / 94 (1.06%)
    0 / 102 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    Arthralgia
         subjects affected / exposed
    29 / 100 (29.00%)
    29 / 104 (27.88%)
    18 / 100 (18.00%)
    19 / 94 (20.21%)
    18 / 102 (17.65%)
         occurrences all number
    42
    34
    21
    26
    18
    Musculoskeletal pain
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    1 / 102 (0.98%)
         occurrences all number
    0
    0
    0
    0
    1
    Tendonitis
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    3 / 94 (3.19%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    1
    4
    0
    Myalgia
         subjects affected / exposed
    50 / 100 (50.00%)
    49 / 104 (47.12%)
    45 / 100 (45.00%)
    41 / 94 (43.62%)
    28 / 102 (27.45%)
         occurrences all number
    75
    67
    64
    59
    28
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 100 (5.00%)
    3 / 104 (2.88%)
    0 / 100 (0.00%)
    3 / 94 (3.19%)
    3 / 102 (2.94%)
         occurrences all number
    5
    3
    0
    3
    3
    Viral infection
         subjects affected / exposed
    2 / 100 (2.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    1 / 102 (0.98%)
         occurrences all number
    2
    1
    0
    0
    1
    Gastroenteritis
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    1 / 94 (1.06%)
    0 / 102 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    Tonsillitis
         subjects affected / exposed
    2 / 100 (2.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    1 / 102 (0.98%)
         occurrences all number
    2
    0
    0
    0
    1
    Bronchitis
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    1 / 102 (0.98%)
         occurrences all number
    0
    0
    1
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    2 / 102 (1.96%)
         occurrences all number
    0
    0
    1
    0
    2
    Lyme disease
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Otitis externa
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Pericoronitis
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    1 / 94 (1.06%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Pharyngitis
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Viral pharyngitis
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Paronychia
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    1 / 100 (1.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Sinusitis
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Oral herpes
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 104 (0.96%)
    0 / 100 (0.00%)
    0 / 94 (0.00%)
    0 / 102 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Acute sinusitis
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 104 (0.00%)
    0 / 100 (0.00%)
    1 / 94 (1.06%)
    0 / 102 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 100 (0.00%)
    3 / 104 (2.88%)
    1 / 100 (1.00%)
    1 / 94 (1.06%)
    0 / 102 (0.00%)
         occurrences all number
    0
    3
    1
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 May 2018
    • The protocol has been updated based on feedback received from the State Institute for Drug Control (SUKL) regarding contraception requirements, ex-clusion of other vaccines before and after study vaccine(s) administration, exclusion of subjects with medical bleeding conditions, and to indicate that paracetamol is the preferred antipyret-ic/analgesic. • The distribution and return of Subject Diaries has been clarified. • The protocol was updated to include the use of a pregnancy notification form and to clarify that paper pregnancy reports will be used. • Clarifications have been made to the analysis pop-ulation definitions and the modeling analysis plans. • Other minor changes have been made to correct typos and improve clarity and alignment within the document.
    29 Aug 2018
    • A tertiary objective was added to allow potential exploratory evaluation of immune responses in-duced by the study vaccine(s) against a panel of strains of Neisseria species in a subset of subjects. • Protocol Clarification Letter 1 was incorporated, which removed reference to a pregnancy electronic case report form. • The window for Subject Diary reminder calls was clarified. • Other minor changes were made to correct typos and improve clarity and alignment within the document.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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