Study to Assess Potential Immune Interference When GlaxoSmithKline (GSK) Biologicals' MenABCWY Vaccine is Administered to Healthy Subjects Aged 10-25 Years

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03587207
• Collaborator: (none)
• Enrollment: 520
• Location: 1
• Arms: 5
• Actual Duration (Months): 5.4
• Patients Per Site Per Month: 97.1

Study Details

Study Description

Brief Summary

The purpose of the current study is to evaluate whether there is immune interference when MenABCWY [consisting of MenACWY lyophilized component and rMenB+OMV NZ (Bexsero) liquid component] is administered to healthy adolescents and adults following a 2-dose vaccination schedule with MenABCWY administered 2 months apart.

Condition or Disease	Intervention/Treatment	Phase
Meningitis, Meningococcal	Biological: MenABCWY vaccine; Biological: rMenB+OMV NZ (Bexsero) vaccine; Biological: MenACWY (Menveo) vaccine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 520 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of Meningococcal MenABCWY Vaccine, and of rMenB+OMV NZ and MenACWY Administered Concomitantly in the Same Arm or in 2 Different Arms, or Alone
• Actual Study Start Date: Jul 9, 2018
• Actual Primary Completion Date: Dec 19, 2018
• Actual Study Completion Date: Dec 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MenABCWY Group 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).	Biological: MenABCWY vaccine; Two doses administered intramuscularly in the deltoid region of the non-dominant arm.
Active Comparator: rMenBOMV+ACWY_S Group 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).	Biological: rMenB+OMV NZ (Bexsero) vaccine; Two doses administered 2 months apart intramuscularly in the deltoid region of the non-dominant arm to subjects randomised to the rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group and rMenBOMV Group; Biological: MenACWY (Menveo) vaccine; Two doses administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomised 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 randomised to the MenACWY Group
Active Comparator: rMenBOMV+ACWY_D Group 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).	Biological: rMenB+OMV NZ (Bexsero) vaccine; Two doses administered 2 months apart intramuscularly in the deltoid region of the non-dominant arm to subjects randomised to the rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group and rMenBOMV Group; Biological: MenACWY (Menveo) vaccine; Two doses administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomised 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 randomised to the MenACWY Group
Active Comparator: rMenBOMV Group 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).	Biological: rMenB+OMV NZ (Bexsero) vaccine; Two doses administered 2 months apart intramuscularly in the deltoid region of the non-dominant arm to subjects randomised to the rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group and rMenBOMV Group
Active Comparator: MenACWY Group 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.	Biological: MenACWY (Menveo) vaccine; Two doses administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomised 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 randomised to the MenACWY Group

Outcome Measures

Primary Outcome Measures

1. 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 month after last vaccination i.e.: at Day 91 for all groups except for the MenACWY Group]

   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.

2. 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. [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.]

   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.

3. 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. [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.]

   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).

4. 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. [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).]

   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).

5. 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. [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).]

   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.

Secondary Outcome Measures

1. hSBA Adjusted GMTs Against All of N. Meningitidis Serogroup B Test Strains (Pooled), One Month After First Vaccination [1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group]

   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.

2. 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. [1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group.]

   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.

3. 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 [1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group]

   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).

4. 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 [1 month after first vaccination versus baseline (i.e.: at Day 31 versus Day 1 for all groups except for the MenACWY Group)]

   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).

5. 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 [1 month after first vaccination versus baseline (i.e.: at Day 31 versus Day 1 for all groups except for the MenACWY Group)]

   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 first 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 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.

6. Number of Subjects With Any Solicited Local Adverse Events (AEs) [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)]

   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.

7. Number of Subjects With Any Solicited Systemic AEs [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)]

   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.

8. Number of Subjects With Unsolicited AEs [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)]

   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.

9. Number of Subjects With Serious Adverse Events (SAEs), Medically Attended AEs (MAEs), AEs Leading to Withdrawal, and Adverse Events of Special Interest (AESIs) [During the whole study period i.e from Day 1 to Day 91]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 25 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects and/or subjects' parent(s)/Legally Acceptable Representative(s) (LARs) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol (e.g. completion of the paper diary (pDiary), return for follow-up visits, availability for all visits scheduled in the study).

• Written informed consent obtained from the subject and/or from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure.

• Written informed assent obtained from subjects below the legal age of consent prior to performing any study specific procedure.

• A male or female between, and including, 10 to 25 years of age at the time of the first vaccination.

• Healthy subjects as established by medical history and clinical examination before entering into the study.

• Female subjects of non-childbearing potential may be enrolled in the study.

• Non-childbearing potential is defined as pre menarche, current bilateral tubal ligation or occlusion, hysterectomy, or bilateral ovariectomy.

• Female subjects of childbearing potential may be enrolled in the study, if the subject:

• has practiced highly effective contraception for 30 days prior to vaccination, and

• has a negative pregnancy test on the day of vaccination, and

• has agreed to continue highly effective contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

• Female planning to become pregnant or planning to discontinue contraceptive precautions

• Pregnant or lactating female

• Child in care

• Current or previous, confirmed or suspected disease caused by N. meningitidis.

• Known contact to an individual with any laboratory confirmed N. meningitidis infection within 60 days prior to enrolment.

• Previous vaccination against N. meningitidis at any time prior to informed consent.

• Progressive, unstable or uncontrolled clinical conditions.

• Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.

• Clinical conditions representing a contraindication to IM vaccination and blood draws.

• Abnormal function of the immune system resulting from:

• Clinical conditions.

• Systemic administration of corticosteroids (oral/intravenous/IM) for more than 14 consecutive days within 90 days prior to informed consent.

• Administration of antineoplastic and immune modulating agents or radiotherapy within 90 days prior to informed consent.

• Received immunoglobulins or any blood products within 180 days prior to informed consent.

• Received an investigational or non registered medicinal product within 30 days prior to informed consent.

• Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study.

• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non investigational vaccine/product.

• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

• Are obese at screening.

• Family history of congenital or hereditary immunodeficiency.

• History of neuroinflammatory or autoimmune condition.

• History of significant neurological disorder or seizure.

• Serious chronic illness.

• History of chronic alcohol consumption and/or drug abuse.

• Any study personnel as an immediate family or household member.

• Administration of a vaccine not foreseen by the study protocol in the period starting 14 days (for inactivated vaccines), 28 days (for live vaccines), or 7 days (for influenza vaccines) before each dose and ending 14 days (for inactivated vaccines), 28 days (for live vaccines), or 7 days (for influenza vaccines) after each dose of study vaccine(s) administration.

• Thrombocytopenia, bleeding disorders, or be receiving anticoagulant therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Hradec Kralove		Czechia	50002

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

Study Documents (Full-Text)

• Study Protocol - Aug 29, 2018
• Statistical Analysis Plan - Jun 15, 2018

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03587207
• Other Study ID Numbers: 208205; 2017-005128-12
• First Posted: Jul 16, 2018
• Last Update Posted: Feb 12, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: Meningitis; Concomitantly; Adolescent; Neisseria meningitidis; Healthy subjects; Adult
• Additional relevant MeSH terms: Meningitis, Meningococcal; Meningitis; Vaccines

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from 1 center at Czechia.
Pre-assignment Detail	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.

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group	MenACWY Group
Arm/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).	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).	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).	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).	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.
Period Title: Overall Study
STARTED	100	104	100	94	102
COMPLETED	100	104	100	94	102
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group	MenACWY Group	Total
Arm/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).	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).	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).	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).	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.	Total of all reporting groups
Overall Participants	100	104	100	94	102	500
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	17.1 (4.34)	16.9 (4.28)	17.1 (4.49)	17.4 (4.64)	17.1 (4.57)	17.1 (4.45)
Sex: Female, Male (Count of Participants)
Female	47 47%	48 46.2%	49 49%	53 56.4%	49 48%	246 49.2%
Male	53 53%	56 53.8%	51 51%	41 43.6%	53 52%	254 50.8%
Race/Ethnicity, Customized (Count of Participants)
WHITE	100 100%	104 100%	100 100%	94 100%	102 100%	500 100%

Outcome Measures

1. Primary Outcome

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.
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.
Time Frame	1 month after last vaccination i.e.: at Day 91 for all groups except for the MenACWY Group

Outcome Measure Data

Analysis Population Description

Analysis performed on Per Protocol Set(PPS) for immunogenicity that included subjects without major protocol violations & whose assay results were available for atleast 1 serogroup/B strain at Day 91 for all study groups except MenACWY group that was not considered for this analysis as only serogroup B strains were assessed in this outcome measure

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group
Arm/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).	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).	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).	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).
Measure Participants	98	100	97	90
Geometric Mean (80% Confidence Interval) [titers]	31.84	38.48	40.08	42.38

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	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.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 80%; 0.83 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

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.
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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group	MenACWY Group
Arm/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).	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).	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).	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).	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.
Measure Participants	98	101	97	90	97
Meningitis B M14459 (fHbp)	23.91	23.34	23.23	22.87	2.48
Meningitis B 96217(NadA)	81.09	102.68	97.54	113.54	4.15
Meningitis B NZ98/254(PorA)	12.97	16.39	21.12	20.97	2.15
Meningitis B M07-0241084(NHBA)	13.08	18.00	22.59	25.34	4.08
Meningitis A	104.90	187.52	204.01	94.91	52.03
Meningitis C	172.99	144.80	145.42	32.01	34.66
Meningitis W	260.11	245.63	254.20	193.58	80.11
Meningitis Y	219.52	186.08	204.92	3.66	92.41

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M14459 strain-Between group ratios for comparison of rMenBOMV+ACWY_S and rMenBOMV+ACWY_D groups
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 80%; 0.84 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	96217 strain-Between group ratios for comparison of rMenBOMV+ACWY_S and rMenBOMV+ACWY_D groups
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.05
	Confidence Interval	() 80%; 0.88 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	NZ98/254 strain-Between group ratios for comparison of rMenBOMV+ACWY_S and rMenBOMV+ACWY_D groups
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 80%; 0.64 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M07-0241084 strain- Between group ratios for comparison of rMenBOMV_ACWY_S group and rMenBOMV+ACWY_D group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 80%; 0.66 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup A- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 80%; 0.74 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup C- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 80%; 0.78 to 1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup W- Between group ratios for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 80%; 0.79 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup Y- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 80%; 0.69 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B M14459 (fHbp) strain, one month after last vaccination.
	Type of Statistical Test	Other
	Comments	M14459 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 80%; 0.86 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B 96217 (NadA)strain, one month after last vaccination.
	Type of Statistical Test	Other
	Comments	96217 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 80%; 0.66 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B NZ98/254 (PorA) strain, one month after last vaccination.
	Type of Statistical Test	Other
	Comments	NZ98/254 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 80%; 0.65 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B M07-0241084 (NHBA) strain, one month after last vaccination.
	Type of Statistical Test	Non-Inferiority
	Comments	M07-0241084 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 80%; 0.60 to 0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogrpoup A, one month after last vaccination.
	Type of Statistical Test	Other
	Comments	Serogroup A- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 80%; 0.45 to 0.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogroup C, one month after last vaccination.
	Type of Statistical Test	Other
	Comments	Serogroup C- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 80%; 0.94 to 1.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogroup W, one month after last vaccination.
	Type of Statistical Test	Other
	Comments	Serogroup W- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 80%; 0.87 to 1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogroup Y, one month after last vaccination.
	Type of Statistical Test	Other
	Comments	Serogroup Y- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 80%; 0.90 to 1.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M14459 strain- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 80%; 0.85 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	96217 strain-Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 80%; 0.75 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	NZ98/254 strain-Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 80%; 0.64 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M07-0241084 strain-Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 80%; 0.58 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, MenACWY Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup A- Between group ratio for comparison of rMenBOMV+ACWY_S group and MenACWY group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	3.60
	Confidence Interval	(2-Sided) 80%; 2.90 to 4.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, MenACWY Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup C- Between group ratio for comparison of rMenBOMV+ACWY_S group and MenACWY group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	4.18
	Confidence Interval	(2-Sided) 80%; 3.28 to 5.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, MenACWY Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup W- Between group ratio for comparison of rMenBOMV+ACWY_S group and MenACWY group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	3.07
	Confidence Interval	(2-Sided) 80%; 2.52 to 3.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, MenACWY Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup Y- Between group ratio for comparison of rMenBOMV+ACWY_S group and MenACWY group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	2.01
	Confidence Interval	(2-Sided) 80%; 1.53 to 2.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_D Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M14459 strain- Between group ratio for comparison of rMenBOMV+ACWY_D group and rMenBOMV group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 80%; 0.85 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_D Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	96217 strain- Between group ratios for comparison of rMenBOMV+ACWY_D group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 80%; 0.71 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_D Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	NZ98/254 strain-Between group ratio for comparison of rMenBOMV+ACWY_D group and rMenBOMV group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 80%; 0.82 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_D Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M07-0241084 strain-Between group ratio for comparison of rMenBOMV+ACWY_D group and rMenBOMV group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 80%; 0.73 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_D Group, MenACWY Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup A-Between group ratio for comparison of rMenBOMV+ACWY_D group and MenACWY group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	3.92
	Confidence Interval	(2-Sided) 80%; 3.15 to 4.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_D Group, MenACWY Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup C- Between group ratio for comparison of rMenBOMV+ACWY_D group and MenACWY group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	4.19
	Confidence Interval	(2-Sided) 80%; 3.30 to 5.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_D Group, MenACWY Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup W- Between group ratio for comparison of rMenBOMV+ACWY_D group and MenACWY group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	3.17
	Confidence Interval	(2-Sided) 80%; 2.60 to 3.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_D Group, MenACWY Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup Y- Between group ratio for comparison of rMenBOMV+ACWY_D group and MenACWY group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	2.22
	Confidence Interval	(2-Sided) 80%; 1.68 to 2.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M14459- Between group ratios for comparison of MenABCWY group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 80%; 0.87 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	96217 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 80%; 0.59 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	NZ98/254 strain-Between group ratios for comparison of MenABCWY group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 80%; 0.50 to 0.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M07-0241084 strain-Between group ratios for comparison of MenABCWY group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 80%; 0.42 to 0.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, MenACWY Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup A- Between group ratios for comparison between MenABCWY group and MenACWY group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	2.02
	Confidence Interval	(2-Sided) 80%; 1.62 to 2.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, MenACWY Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup C- Between group ratios for comparison of MenABCWY group and MenACWY group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.99
	Confidence Interval	(2-Sided) 80%; 3.92 to 6.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, MenACWY Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup W- Between group ratios for comparison of MenABCWY group and MenACWY group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	3.25
	Confidence Interval	(2-Sided) 80%; 2.66 to 3.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, MenACWY Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup Y- Between group ratio for comparison of MenABCWY group and MenACWY group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	2.38
	Confidence Interval	(2-Sided) 80%; 1.81 to 3.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

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.
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).
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group	MenACWY Group
Arm/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).	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).	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).	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).	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.
Measure Participants	98	101	97	90	97
Meningitis B M14459 (fHbp)	83.5	86.0	88.5	83.3	12.4
Mengitis B 96217(NadA)	96.9	99.0	99.0	100.0	33.3
Meningitis B NZ98/254 (PorA)	59.2	76.0	80.4	78.7	5.2
Meningitis B M07-0241084 (NHBA)	59.2	74.0	77.1	80.9	23.2
Meningitis A	94.8	100.0	99.0	91.1	68.8
Meningitis C	100.0	100.0	100.0	96.7	86.6
Meningitis W	98.0	96.0	99.0	93.3	66.0
Menngitis Y	99.0	98.0	96.9	24.7	85.4

4. Primary Outcome

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.
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).
Time Frame	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).

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group	MenACWY Group
Arm/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).	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).	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).	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).	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.
Measure Participants	98	100	97	90	97
Meningitis B M14459 (fHbp)	66.0	69.0	66.3	63.3	2.1
Meningitis B 96217(NadA)	80.4	88.0	90.5	80.7	2.1
Meningitis B NZ98/254 (PorA)	48.0	60.0	58.8	60.7	1.0
Meningitis B M07-0241084(NHBA)	21.4	38.8	42.1	56.3	2.1
Meningitis A	92.7	99.0	98.9	87.8	67.4
Meningitis C	90.8	91.9	86.6	57.3	52.1
Meningitis W	83.3	78.6	74.2	74.1	41.1
Meningitis Y	95.9	91.9	93.7	11.4	76.8

5. Primary Outcome

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.
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.
Time Frame	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).

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group	MenACWY Group
Arm/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).	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).	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).	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).	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.
Measure Participants	98	100	97	90	97
Meningitis B M14459 (fHbp)	11.17	10.90	10.85	10.69	1.16
Meningitis B 96217(NadA)	21.33	27.02	25.66	29.87	1.09
Meningitis B NZ98/254(PorA)	7.28	9.20	11.85	11.77	1.21
Meningitis B M07-0241084(NHBA)	3.60	4.96	6.22	6.98	1.12
Meningitis A	33.21	59.36	64.58	30.05	16.47
Meningitis C	34.34	28.74	28.86	6.35	6.88
Meningitis W	24.58	23.21	24.02	18.29	7.57
Meningitis Y	106.87	90.59	99.76	1.78	44.99

6. Secondary Outcome

Title	hSBA Adjusted GMTs Against All of N. Meningitidis Serogroup B Test Strains (Pooled), One Month After First Vaccination
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.
Time Frame	1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group
Arm/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).	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).	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).	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).
Measure Participants	96	103	98	91
Geometric Mean (80% Confidence Interval) [Titers]	6.51	8.33	8.16	9.45

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	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.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 80%; 0.86 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

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.
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.
Time Frame	1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group.

Outcome Measure Data

Analysis Population Description

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/ 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).

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group
Arm/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).	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).	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).	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).
Measure Participants	96	103	98	91
Meningitis B M14459(fHbp)	5.50	6.36	4.94	6.08
Meningitis B 96217 (NadA)	8.21	11.30	12.18	14.07
Meningitis B NZ98/254 (PorA)	3.79	4.83	4.76	5.48
Meningitis B M07-0241084 (NHBA)	6.27	7.31	6.75	7.69
Meningitis A	31.38	67.95	88.29	8.22
Meningitis C	41.35	33.76	40.33	11.47
Meningitis W	108.91	81.38	92.84	42.99
Meningitis Y	75.07	76.48	100.30	3.98

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M14459 strain- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 80%; 1.02 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	96217 strain- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 80%; 0.75 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	NZ98/254 strain- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 80%; 0.80 to 1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M07-0241084 strain-Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 80%; 0.87 to 1.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup A- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 80%; 0.58 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup C- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D Group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 80%; 0.62 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup W- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 80%; 0.68 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV+ACWY_D Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	Serogroup Y- Between group ratio for comparison of rMenBOMV+ACWY_S group and rMenBOMV+ACWY_D group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 80%; 0.54 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B M14459 (fHbp) strain, one month after first vaccination.
	Type of Statistical Test	Other
	Comments	M14459 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 80%; 0.69 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B 96217 (NadA) strain, one month after first vaccination.
	Type of Statistical Test	Other
	Comments	96217 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 80%; 0.58 to 0.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B NZ98/254 (PorA) strain, one month after first vaccination.
	Type of Statistical Test	Other
	Comments	NZ98/254 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 80%; 0.61 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis B M07-0241084 (NHBA) strain, one month after first vaccination.
	Type of Statistical Test	Other
	Comments	M07-0241084 strain- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 80%; 0.68 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogroup A, one month after first vaccination.
	Type of Statistical Test	Other
	Comments	Serogroup A- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 80%; 0.35 to 0.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogroup C, one month after first vaccination.
	Type of Statistical Test	Other
	Comments	Serogroup C- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 80%; 0.91 to 1.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogroup W, one month after first vaccination.
	Type of Statistical Test	Other
	Comments	Serogroup W- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.34
	Confidence Interval	(2-Sided) 80%; 1.04 to 1.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV+ACWY_S Group
	Comments	Other unknown interference in MenABCWY versus rMenBOMV+ACWY_S study groups, on the Meningitis serogroup Y, one month after first vaccination.
	Type of Statistical Test	Other
	Comments	Serogroup Y- Between group ratio for comparison of MenABCWY group and rMenBOMV+ACWY_S group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 80%; 0.70 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M14459 strain-Between group ratio for comparison of rMenBOMV_ACWY_S group and rMenBOMV group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 80%; 0.83 to 1.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	96217 strain-Between group ratio for comparison of rMenBOMV_ACWY_S group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 80%; 0.64 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	NZ98/254 strain -Between group ratio for comparison of rMenBOMV_ACWY_S group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 80%; 0.69 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_S Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M07-0241084 strain -Between group ratio for comparison of rMenBOMV_ACWY_S group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 80%; 0.76 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_D Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M14459 strain -Between group ratio for comparison of rMenBOMV_ACWY_D group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 80%; 0.64 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_D Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	96217 strain -Between group ratio for comparison of rMenBOMV_ACWY_D group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 80%; 0.69 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_D Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	NZ98/254 strain -Between group ratio for comparison of rMenBOMV_ACWY_D group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometrical mean ratio
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 80%; 0.68 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	rMenBOMV+ACWY_D Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M07-0241084 strain-Between group ratio for comparison of rMenBOMV_ACWY_D group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometrical mean ratio
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 80%; 0.70 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M14459 strain-Between group ratio for comparison of MenABCWY group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 80%; 0.71 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	96217 strain-Between group ratio for comparison of MenABCWY group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 80%; 0.47 to 0.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	NZ98/254 strain-Between group ratio for comparison of MenABCWY group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 80%; 0.54 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, rMenBOMV Group
	Comments	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.
	Type of Statistical Test	Other
	Comments	M07-0241084 strain-Between group ratio for comparison of MenABCWY group and rMenBOMV group
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 80%; 0.65 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

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
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).
Time Frame	1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group

Outcome Measure Data

Analysis Population Description

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/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).

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group
Arm/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).	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).	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).	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).
Measure Participants	96	103	98	91
Meningitis B M14459 (fHbp)	36.8	49.5	37.8	42.2
Meningitis B 96217 (NadA)	57.3	66.0	69.4	75.8
Meningitis B NZ98/254 (PorA)	29.2	37.9	33.7	37.8
Meningitis B M07-0241084 (NHBA)	35.1	49.5	37.5	44.4
Meningitis A	65.3	73.5	80.2	25.6
Meningitis C	89.6	94.1	92.8	70.0
Meningitis W	71.9	70.6	74.2	52.3
Meningitis Y	83.2	81.8	88.4	20.0

9. Secondary Outcome

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
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).
Time Frame	1 month after first vaccination versus baseline (i.e.: at Day 31 versus Day 1 for all groups except for the MenACWY Group)

Outcome Measure Data

Analysis Population Description

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/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 4).

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group
Arm/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).	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).	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).	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).
Measure Participants	96	103	97	91
Meningitis B M14459 (fHbp)	24.2	24.3	18.8	25.6
Meningitis B 96217 (NadA)	22.1	34.0	30.5	32.6
Meningitis B NZ98/254 (PorA)	20.8	26.2	26.8	27.8
Meningitis B M07-0241084 (NHBA)	9.6	20.6	13.8	20.5
Meningitis A	61.7	71.3	80.6	23.3
Meningitis C	54.2	46.5	51.0	24.7
Meningitis W	60.6	52.0	51.6	39.8
Meningitis Y	77.9	75.5	78.3	9.0

10. Secondary Outcome

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
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 first 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 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.
Time Frame	1 month after first vaccination versus baseline (i.e.: at Day 31 versus Day 1 for all groups except for the MenACWY Group)

Outcome Measure Data

Analysis Population Description

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/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).

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group
Arm/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).	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).	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).	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).
Measure Participants	96	103	97	90
Meningitis B M14459 (fHbp)	2.59	3.00	2.33	2.87
Meningitis B 96217(NadA)	2.15	2.96	3.19	3.68
Meningitis B NZ98/254 (PorA)	2.16	2.76	2.72	3.13
Meningitis B M07-0241084 (NHBA)	1.73	2.01	1.86	2.12
Meningitis A	10.15	21.97	28.55	2.66
Meningitis C	8.08	6.59	7.88	2.24
Meningitis W	11.08	8.28	9.44	4.37
Meningitis Y	36.58	37.26	48.87	1.94

11. Secondary Outcome

Title	Number of Subjects With Any Solicited Local Adverse Events (AEs)
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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Analysis was performed on solicited safety set that included all subjects who provided informed consent,underwent screening procedures,had a subject number assigned,received a study vaccination & 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.

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group	MenACWY Group
Arm/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).	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).	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).	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).	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.
Measure Participants	100	104	100	94	102
Erythema at Dose 1	17 17%	19 18.3%	18 18%	9 9.6%	7 6.9%
Swelling at Dose 1	20 20%	21 20.2%	16 16%	13 13.8%	10 9.8%
Induration at Dose 1	9 9%	15 14.4%	12 12%	6 6.4%	4 3.9%
Pain at Dose 1	89 89%	100 96.2%	95 95%	88 93.6%	52 51%
Erythema at Dose 2	15 15%	18 17.3%	15 15%	10 10.6%
Swelling at Dose 2	13 13%	14 13.5%	15 15%	12 12.8%
Induration at Dose 2	6 6%	11 10.6%	12 12%	12 12.8%
Pain at Dose 2	87 87%	97 93.3%	95 95%	87 92.6%

12. Secondary Outcome

Title	Number of Subjects With Any Solicited Systemic AEs
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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Analysis was performed on solicited safety set that included all subjects who provided informed consent,underwent screening procedures,had a subject number assigned,received a study vaccination & 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.

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group	MenACWY Group
Arm/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).	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).	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).	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).	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.
Measure Participants	100	104	100	94	102
Arthralgia at Dose 1	20 20%	15 14.4%	9 9%	9 9.6%	18 17.6%
Fatigue at Dose 1	56 56%	61 58.7%	55 55%	46 48.9%	50 49%
Nausea at Dose 1	16 16%	23 22.1%	14 14%	13 13.8%	14 13.7%
Headache at Dose 1	40 40%	46 44.2%	38 38%	36 38.3%	36 35.3%
Myalgia at Dose 1	34 34%	29 27.9%	27 27%	21 22.3%	28 27.5%
Fever at Dose 1	6 6%	5 4.8%	5 5%	1 1.1%	3 2.9%
Arthralgia at Dose 2	22 22%	19 18.3%	12 12%	17 18.1%
Fatigue at Dose 2	58 58%	61 58.7%	62 62%	56 59.6%
Nausea at Dose 2	16 16%	13 12.5%	15 15%	17 18.1%
Headache at Dose 2	52 52%	36 34.6%	37 37%	39 41.5%
Myalgia at Dose 2	41 41%	38 36.5%	35 35%	38 40.4%
Fever at Dose 2	6 6%	3 2.9%	3 3%	1 1.1%

13. Secondary Outcome

Title	Number of Subjects With Unsolicited AEs
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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Analysis was performed on unsolicited safety set that included all subjects who provided informed consent,underwent screening procedures,had a subject number assigned,received any study vaccination & was reported with any unsolicited AE data.No results for dose 2 category for subjects of MenACWY Group as they received only 1 dose at day 1.

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group	MenACWY Group
Arm/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).	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).	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).	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).	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.
Measure Participants	100	104	100	94	102
Any unsolicited AEs- Dose 1	16 16%	19 18.3%	16 16%	16 17%	15 14.7%
Any unsolicited AEs- Dose 2	11 11%	14 13.5%	13 13%	10 10.6%

14. Secondary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs), Medically Attended AEs (MAEs), AEs Leading to Withdrawal, and Adverse Events of Special Interest (AESIs)
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.
Time Frame	During the whole study period i.e from Day 1 to Day 91

Outcome Measure Data

Analysis Population Description

Analysis was performed on the unsolicited safety set that included all subjects who provided informed consent, underwent screening procedures, had a subject number assigned, received any study vaccination and was reported with any adverse event data.

Arm/Group Title	MenABCWY Group	rMenBOMV+ACWY_S Group	rMenBOMV+ACWY_D Group	rMenBOMV Group	MenACWY Group
Arm/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).	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).	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).	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).	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.
Measure Participants	100	104	100	94	102
SAE(s)	0 0%	2 1.9%	1 1%	2 2.1%	0 0%
MAE(s)	14 14%	17 16.3%	14 14%	13 13.8%	6 5.9%
AE(s) leading to withdrawal	0 0%	0 0%	0 0%	0 0%	0 0%
AESI(s)	0 0%	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	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).
Arm/Group Title	MenABCWY Group		rMenBOMV+ACWY_S Group		rMenBOMV+ACWY_D Group		rMenBOMV Group		MenACWY Group
Arm/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).		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).		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).		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).		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.
All Cause Mortality
	MenABCWY Group		rMenBOMV+ACWY_S Group		rMenBOMV+ACWY_D Group		rMenBOMV Group		MenACWY Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/100 (0%)		0/104 (0%)		0/100 (0%)		0/94 (0%)		0/102 (0%)
Serious Adverse Events
	MenABCWY Group		rMenBOMV+ACWY_S Group		rMenBOMV+ACWY_D Group		rMenBOMV Group		MenACWY Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/100 (0%)		2/104 (1.9%)		1/100 (1%)		2/94 (2.1%)		0/102 (0%)
Injury, poisoning and procedural complications
Concussion	0/100 (0%)	0	2/104 (1.9%)	2	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Lower limb fracture	0/100 (0%)	0	0/104 (0%)	0	0/100 (0%)	0	1/94 (1.1%)	1	0/102 (0%)	0
Tibia fracture	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	0/102 (0%)	0
Nervous system disorders
Syncope	0/100 (0%)	0	0/104 (0%)	0	0/100 (0%)	0	1/94 (1.1%)	1	0/102 (0%)	0
Other (Not Including Serious) Adverse Events
	MenABCWY Group		rMenBOMV+ACWY_S Group		rMenBOMV+ACWY_D Group		rMenBOMV Group		MenACWY Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	94/100 (94%)		103/104 (99%)		98/100 (98%)		94/94 (100%)		80/102 (78.4%)
Ear and labyrinth disorders
Vertigo	1/100 (1%)	1	0/104 (0%)	0	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Gastrointestinal disorders
Toothache	1/100 (1%)	1	1/104 (1%)	1	0/100 (0%)	0	2/94 (2.1%)	2	1/102 (1%)	1
Abdominal pain	0/100 (0%)	0	1/104 (1%)	1	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Anal fissure	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	0/102 (0%)	0
Dyspepsia	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	0/102 (0%)	0
Enteritis	1/100 (1%)	1	0/104 (0%)	0	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Gastritis	0/100 (0%)	0	1/104 (1%)	1	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Nausea	24/100 (24%)	32	26/104 (25%)	36	26/100 (26%)	29	26/94 (27.7%)	30	14/102 (13.7%)	14
Diarrhoea	0/100 (0%)	0	1/104 (1%)	1	0/100 (0%)	0	0/94 (0%)	0	2/102 (2%)	2
General disorders
Face oedema	0/100 (0%)	0	0/104 (0%)	0	0/100 (0%)	0	1/94 (1.1%)	1	0/102 (0%)	0
Fatigue	70/100 (70%)	114	74/104 (71.2%)	122	72/100 (72%)	117	63/94 (67%)	102	50/102 (49%)	50
Inflammation	1/100 (1%)	1	0/104 (0%)	0	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Injection site pain	94/100 (94%)	176	102/104 (98.1%)	197	97/100 (97%)	190	93/94 (98.9%)	175	53/102 (52%)	53
Erythema	50/100 (50%)	78	71/104 (68.3%)	108	57/100 (57%)	82	58/94 (61.7%)	81	28/102 (27.5%)	28
Swelling	51/100 (51%)	80	63/104 (60.6%)	98	46/100 (46%)	69	46/94 (48.9%)	65	23/102 (22.5%)	23
Induration	44/100 (44%)	65	54/104 (51.9%)	85	49/100 (49%)	72	38/94 (40.4%)	56	19/102 (18.6%)	19
Pyrexia	12/100 (12%)	13	7/104 (6.7%)	8	8/100 (8%)	8	2/94 (2.1%)	2	3/102 (2.9%)	3
Injection site induration	2/100 (2%)	2	5/104 (4.8%)	5	1/100 (1%)	1	4/94 (4.3%)	4	0/102 (0%)	0
Injection site erythema	2/100 (2%)	2	3/104 (2.9%)	3	4/100 (4%)	4	1/94 (1.1%)	1	0/102 (0%)	0
Injection site swelling	3/100 (3%)	4	2/104 (1.9%)	2	1/100 (1%)	1	1/94 (1.1%)	1	0/102 (0%)	0
Vaccination site erythema	0/100 (0%)	0	0/104 (0%)	0	3/100 (3%)	3	0/94 (0%)	0	1/102 (1%)	1
Vaccination site swelling	0/100 (0%)	0	0/104 (0%)	0	2/100 (2%)	2	0/94 (0%)	0	2/102 (2%)	2
Vaccination site induration	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	1/102 (1%)	1
Injection site hypersensitivity	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	0/102 (0%)	0
Injection site discolouration	1/100 (1%)	1	0/104 (0%)	0	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Immune system disorders
Food allergy	0/100 (0%)	0	0/104 (0%)	0	0/100 (0%)	0	0/94 (0%)	0	1/102 (1%)	1
Infections and infestations
Upper respiratory tract infection	5/100 (5%)	5	3/104 (2.9%)	3	0/100 (0%)	0	3/94 (3.2%)	3	3/102 (2.9%)	3
Viral infection	2/100 (2%)	2	1/104 (1%)	1	0/100 (0%)	0	0/94 (0%)	0	1/102 (1%)	1
Gastroenteritis	1/100 (1%)	1	0/104 (0%)	0	1/100 (1%)	1	1/94 (1.1%)	1	0/102 (0%)	0
Tonsillitis	2/100 (2%)	2	0/104 (0%)	0	0/100 (0%)	0	0/94 (0%)	0	1/102 (1%)	1
Bronchitis	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	1/102 (1%)	1
Rhinitis	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	2/102 (2%)	2
Lyme disease	0/100 (0%)	0	1/104 (1%)	1	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Otitis externa	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	0/102 (0%)	0
Skin infection	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	0/102 (0%)	0
Pericoronitis	0/100 (0%)	0	0/104 (0%)	0	0/100 (0%)	0	1/94 (1.1%)	1	0/102 (0%)	0
Pharyngitis	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	0/102 (0%)	0
Pharyngitis streptococcal	0/100 (0%)	0	1/104 (1%)	1	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Viral pharyngitis	1/100 (1%)	1	0/104 (0%)	0	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Paronychia	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	0/102 (0%)	0
Respiratory tract infection viral	0/100 (0%)	0	1/104 (1%)	1	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Sinusitis	1/100 (1%)	1	0/104 (0%)	0	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Oral herpes	0/100 (0%)	0	1/104 (1%)	1	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Acute sinusitis	0/100 (0%)	0	0/104 (0%)	0	0/100 (0%)	0	1/94 (1.1%)	1	0/102 (0%)	0
Nasopharyngitis	0/100 (0%)	0	3/104 (2.9%)	3	1/100 (1%)	1	1/94 (1.1%)	1	0/102 (0%)	0
Injury, poisoning and procedural complications
Ligament sprain	1/100 (1%)	1	0/104 (0%)	0	0/100 (0%)	0	2/94 (2.1%)	2	0/102 (0%)	0
Arthropod bite	0/100 (0%)	0	0/104 (0%)	0	0/100 (0%)	0	1/94 (1.1%)	1	0/102 (0%)	0
Contusion	0/100 (0%)	0	0/104 (0%)	0	0/100 (0%)	0	1/94 (1.1%)	1	0/102 (0%)	0
Foot fracture	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	0/102 (0%)	0
Head injury	0/100 (0%)	0	1/104 (1%)	1	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Limb injury	0/100 (0%)	0	1/104 (1%)	1	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Thermal burn	0/100 (0%)	0	1/104 (1%)	1	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Arthropod sting	1/100 (1%)	1	0/104 (0%)	0	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Vaccination complication	2/100 (2%)	2	0/104 (0%)	0	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Investigations
Weight decreased	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	0/102 (0%)	0
Weight increased	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	0/102 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/100 (0%)	0	1/104 (1%)	1	1/100 (1%)	1	1/94 (1.1%)	1	0/102 (0%)	0
Arthralgia	29/100 (29%)	42	29/104 (27.9%)	34	18/100 (18%)	21	19/94 (20.2%)	26	18/102 (17.6%)	18
Musculoskeletal pain	0/100 (0%)	0	0/104 (0%)	0	0/100 (0%)	0	0/94 (0%)	0	1/102 (1%)	1
Tendonitis	1/100 (1%)	1	0/104 (0%)	0	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Pain in extremity	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	3/94 (3.2%)	4	0/102 (0%)	0
Myalgia	50/100 (50%)	75	49/104 (47.1%)	67	45/100 (45%)	64	41/94 (43.6%)	59	28/102 (27.5%)	28
Nervous system disorders
Migraine	0/100 (0%)	0	2/104 (1.9%)	2	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Syncope	0/100 (0%)	0	2/104 (1.9%)	2	0/100 (0%)	0	2/94 (2.1%)	2	1/102 (1%)	1
Headache	60/100 (60%)	92	57/104 (54.8%)	82	54/100 (54%)	75	52/94 (55.3%)	75	36/102 (35.3%)	36
Dizziness	1/100 (1%)	1	1/104 (1%)	1	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Paraesthesia	1/100 (1%)	1	0/104 (0%)	0	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Psychiatric disorders
Depression	1/100 (1%)	1	0/104 (0%)	0	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Reproductive system and breast disorders
Dysmenorrhoea	0/100 (0%)	0	0/104 (0%)	0	1/100 (1%)	1	0/94 (0%)	0	0/102 (0%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/100 (0%)	0	1/104 (1%)	1	1/100 (1%)	1	1/94 (1.1%)	1	0/102 (0%)	0
Skin and subcutaneous tissue disorders
Urticaria	1/100 (1%)	1	1/104 (1%)	1	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Eczema	0/100 (0%)	0	1/104 (1%)	1	0/100 (0%)	0	0/94 (0%)	0	0/102 (0%)	0
Erythema	0/100 (0%)	0	0/104 (0%)	0	0/100 (0%)	0	1/94 (1.1%)	1	0/102 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.