Effectiveness of GlaxoSmithKline Biologicals S.A's Meningococcal Group B and Combined ABCWY Vaccines in Healthy Adolescents and Young Adults

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness of 2 doses or 3 doses of GSK's licenced meningococcal group B Bexsero (rMenB+OMV NZ) vaccine and of 2 doses of GSK's investigational combined meningococcal (MenABCWY) vaccine (GSK3536819A) in healthy adolescents and young adults. The immunogenicity and safety will also be evaluated in the study.

Detailed Description
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As per the feedback from Center for Biologics Evaluation and Research (CBER) the scope of this post-marketing commitment study has been extended to demonstrate the effectiveness, immunogenicity and safety of GSK's investigational combined meningococcal ABCWY vaccine along with the rMenB+OMV NZ vaccine. Note that the rMenB+OMV and MenACWY vaccines provided to MenB_0_2_6, MenB_0_6 group and MenACWY group respectively at day 211 are only as part of standard care of treatment and to maintain blinding. These vaccination schedules are not considered for any endpoint evaluations.

Official Title
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A Phase III, Randomized, Controlled, Observer-blind Study to Demonstrate Effectiveness, Immunogenicity and Safety of GSK's Meningococcal Group B and Combined ABCWY Vaccines When Administered to Healthy Adolescents and Young Adults

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Combination Product: rMenB+OMV NZ vaccine
* Biological: Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY)
* Combination Product: Placebo
* Combination Product: MenABCWY-1
* Combination Product: MenABCWY-2
* Combination Product: MenABCWY-3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects or/and subjects' parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply with the requirements of the protocol. Written or witnessed/thumb printed informed consent obtained from the subject/parent(s)/LAR(s) of the subject prior to performance of any study specific procedure. Written informed assent obtained from the subject (if applicable) prior to performing any study specific procedure. A male or female between, and including, 10 and 25 years of age (i.e. 25 years + 364 days) at the time of the first vaccination. Healthy subjects as established by medical history physical examination and clinical judgment of the investigator before entering into the study. Subjects who are either unvaccinated with MenACWY vaccine or have received a single previous dose of MenACWY vaccine can participate in the study, if they have received it at least 4 years prior to informed consent and assent as applicable (with the exception of meningococcal C vaccination, if the last dose of MenC was received at ≤24 months of age). 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, bilateral ovariectomy or post-menopause*. Female subjects of childbearing potential may be enrolled in the study, if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception until 30 days after completion of Visit 6. A female is considered to be of non-childbearing potential prior to menarche and after natural or induced menopause. Natural menopause is recognized to have occurred after 12 consecutive months of amenorrhea for which there is no other obvious pathological or physiological cause. Induced menopause is recognized to have occurred after hysterectomy, after bilateral oophorectomy, or iatrogenic ablation of ovarian function. Exclusion Criteria: Medical conditions Current or previous, confirmed or suspected disease caused by N. meningitidis. Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis infection within 60 days of enrolment. Progressive, unstable or uncontrolled clinical conditions. Clinical conditions representing a contraindication to intramuscular vaccination and blood draws. Any neuroinflammatory, congenital neurological conditions, encephalopathies, seizures. History of febrile convulsions should not lead to exclusion. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s)/product(s). Hypersensitivity, including allergy, to any component of vaccines, including diphtheria toxoid (CRM 197) and latex medicinal products or medical equipment whose use is foreseen in this study. Abnormal function or modification of the immune system resulting from: Autoimmune disorders or immunodeficiency syndromes. Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to study vaccination until the post-vaccination 3 blood sample (Visit 6). This will mean prednisone - ≥20 mg/day (for adult subjects) or ≥0.5 mg/kg/day (for paediatric subjects), or equivalent. Inhaled and topical steroids are allowed. Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to study vaccination. Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab). Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Prior/Concomitant therapy Use of any investigational or non-registered product other than the study vaccine(s)/product(s) during the period starting 30 days before the first dose of study vaccine(s)/product(s) (Day -29 to Day 1), or planned use during the study period. Previous vaccination against any group B meningococcal vaccine at any time prior to informed consent and assent as applicable. Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the first dose of study vaccine/ product or planned administration during the study period until the post-vaccination 3 blood sample (Visit 6). Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the vaccine/product dose(s) until the post-vaccination 3 blood sample (Visit 6). For corticosteroids, this will mean prednisone ≥20 mg/day (for adult subjects) or ≥0.5 mg/kg/day (for paediatric subjects), or equivalent. Inhaled and topical steroids are allowed. Prior/Concurrent clinical study experience • 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. Other exclusions Child in care. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions. History of /current chronic alcohol abuse and/or drug abuse as determined by the investigator. Any study personnel or immediate dependants, family, or household member.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MenB_0_2_6 Group<br>Participants receive rMenB+OMV NZ vaccine as 3 dose schedule at Day 1, 61 and Day 181 or as 2 dose schedule at Day 1 and Day 61 and 1 dose of MenACWY vaccine at Day 211. | Combination Product: rMenB+OMV NZ vaccine<br>* rMenB+OMV NZ vaccine is administered intramuscularly to the non-dominant arm as 3 doses in a 0,2,6-M schedule or as 2 doses in a 0,6-M schedule to participants in the MenB_0_2_6 Group, as 2 doses in a 0,6-M schedule to participants in the MenB_0_6 Group and as 2 doses at Day 181 and Day 211 to participants in the ACWY Group.<br>* Other names: Bexsero;Biological: Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY)<br>* MenACWY vaccine is administered intramuscularly to the non-dominant arm as 1 dose at Day 211 to participants in the MenB_0_2_6 Group, as 1 dose at Day 61 to participants in the MenB_0_6 Group and as 1 dose at Day 1 to participants in the ACWY Group.<br>* Other names: Menveo;|
| Experimental: MenB_0_6 Group<br>Participants receive rMenB+OMV NZ vaccine as 2 dose schedule at Day 1, and Day 181, 1 dose of MenACWY vaccine at Day 61 and 1 dose of Placebo at Day 211. | Combination Product: rMenB+OMV NZ vaccine<br>* rMenB+OMV NZ vaccine is administered intramuscularly to the non-dominant arm as 3 doses in a 0,2,6-M schedule or as 2 doses in a 0,6-M schedule to participants in the MenB_0_2_6 Group, as 2 doses in a 0,6-M schedule to participants in the MenB_0_6 Group and as 2 doses at Day 181 and Day 211 to participants in the ACWY Group.<br>* Other names: Bexsero;Biological: Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY)<br>* MenACWY vaccine is administered intramuscularly to the non-dominant arm as 1 dose at Day 211 to participants in the MenB_0_2_6 Group, as 1 dose at Day 61 to participants in the MenB_0_6 Group and as 1 dose at Day 1 to participants in the ACWY Group.<br>* Other names: Menveo;Combination Product: Placebo<br>* Placebo is administered intramuscularly to the non-dominant arm as 1 dose at Day 211 to participants in the MenB_0_6 Group, 2 doses at Day 61 and Day 211 to participants in the ABCWY groups and as 1 dose at Day 61 to participants in the ACWY Group.<br>* Other names: NaCl, saline solution;|
| Experimental: ABCWY-1 Group<br>Participants receive 2 doses of MenABCWY lot 1 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211. | Combination Product: Placebo<br>* Placebo is administered intramuscularly to the non-dominant arm as 1 dose at Day 211 to participants in the MenB_0_6 Group, 2 doses at Day 61 and Day 211 to participants in the ABCWY groups and as 1 dose at Day 61 to participants in the ACWY Group.<br>* Other names: NaCl, saline solution;Combination Product: MenABCWY-1<br>* Lot 1 of the MenABCWY vaccine is administered intramuscularly to the non-dominant arm as 2 doses at Day 1 and Day 181 to participants in the ABCWY-1 Group.<br>|
| Experimental: ABCWY-2 Group<br>Participants receive 2 doses of MenABCWY lot 2 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211. | Combination Product: Placebo<br>* Placebo is administered intramuscularly to the non-dominant arm as 1 dose at Day 211 to participants in the MenB_0_6 Group, 2 doses at Day 61 and Day 211 to participants in the ABCWY groups and as 1 dose at Day 61 to participants in the ACWY Group.<br>* Other names: NaCl, saline solution;Combination Product: MenABCWY-2<br>* Lot 2 of the MenABCWY vaccine is administered intramuscularly to the non-dominant arm as 2 doses at Day 1 and Day 181 to participants in the ABCWY-2 Group.<br>|
| Experimental: ABCWY-3 Group<br>Participants receive 2 doses of MenABCWY lot 3 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211. | Combination Product: Placebo<br>* Placebo is administered intramuscularly to the non-dominant arm as 1 dose at Day 211 to participants in the MenB_0_6 Group, 2 doses at Day 61 and Day 211 to participants in the ABCWY groups and as 1 dose at Day 61 to participants in the ACWY Group.<br>* Other names: NaCl, saline solution;Combination Product: MenABCWY-3<br>* Lot 3 of the MenABCWY vaccine is administered intramuscularly to the non-dominant arm as 2 doses at Day 1 and Day 181 to participants in the ABCWY-3 Group.<br>|
| Active Comparator: ACWY Group<br>Participants, receive 1 dose of MenACWY vaccine at Day 1, 1 dose of placebo at Day 61 and 2 doses of rMenB+OMV NZ vaccine at Day 181 and Day 211. | Combination Product: rMenB+OMV NZ vaccine<br>* rMenB+OMV NZ vaccine is administered intramuscularly to the non-dominant arm as 3 doses in a 0,2,6-M schedule or as 2 doses in a 0,6-M schedule to participants in the MenB_0_2_6 Group, as 2 doses in a 0,6-M schedule to participants in the MenB_0_6 Group and as 2 doses at Day 181 and Day 211 to participants in the ACWY Group.<br>* Other names: Bexsero;Biological: Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY)<br>* MenACWY vaccine is administered intramuscularly to the non-dominant arm as 1 dose at Day 211 to participants in the MenB_0_2_6 Group, as 1 dose at Day 61 to participants in the MenB_0_6 Group and as 1 dose at Day 1 to participants in the ACWY Group.<br>* Other names: Menveo;Combination Product: Placebo<br>* Placebo is administered intramuscularly to the non-dominant arm as 1 dose at Day 211 to participants in the MenB_0_6 Group, 2 doses at Day 61 and Day 211 to participants in the ABCWY groups and as 1 dose at Day 61 to participants in the ACWY Group.<br>* Other names: NaCl, saline solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of samples without bactericidal serum activity against each of the endemic US N. meningitidis serogroup B strains at 1 month after the 3-dose (0,2,6-M), the 2-dose [(0,6-M) and (0,2-M)] vaccination schedule of rMenB+OMV and 1 dose of MenACWY | The effectiveness (test-based) of rMenB+OMV vaccine at 1 month after the 3 and 2 doses in MenB_0_2_6 group and 1 month after the 2 dose schedule in MenB_0_6 group when compared to one dose of MenACWY vaccination in ACWY group, against a panel of N. meningitidis serogroup B strains is measured in terms of percentage of samples without bactericidal activity using endogenous complement human Serum Bactericidal Assay (enc-hSBA), which provides a qualitative assessment (yes/no) of the presence of sufficient bactericidal antibodies in human sera to kill a meningococcal strain at a specific dilution of 1:4. The percentage of samples are averaged across all 110 strains. | At 1 month after vaccination schedule (i.e., Day 211 for MenB_0_2_6 group [3-dose schedule] and MenB_0_6 group, Day 91 for the MenB_0_2_6 group [2-dose schedule] for rMenB+OMV vaccine and Day 31 for ACWY group for MenACWY vaccine) | 
| Percentage of participants whose sera kill ≥70% of the strains tested using enc-hSBA at 1 month after the 3-dose schedule (0,2,6-M) and 2-dose schedule ([0,6-M] and [0,2-M]) of rMenB+OMV vaccine | The effectiveness (responder-based) of the rMenB+OMV NZ vaccine is measured in terms of percentage of participants whose sera kill ≥70% of the strains tested using enc-hSBA, being calculated based on Clopper Pearson method. | At 1 month after vaccination schedule (i.e., Day 211 for MenB_0_2_6 group [3-dose schedule] and MenB_0_6 group, Day 91 for the MenB_0_2_6 group [2-dose schedule]) | 
| Geometric mean titers (GMTs) against serogroups A, C, W and Y for each lot (ABCWY-1 Group, ABCWY-2 Group and ABCWY-3 Group) at 1 month after the last vaccination of MenABCWY | Immune responses of 3 lots of the MenACWY component of the MenABCWY vaccine is measured in terms of hSBA GMTs directed against serogroups A, C, W and Y | At Day 211 | 
| Percentage of participants with 4-fold rise in hSBA titers against N. meningitidis serogroups A, C, W and Y at 1 month after last MenABCWY vaccination (pooled lots) and MenACWY vaccination (for the ACWY Group), relative to baseline | The immunogenicity of the MenABCWY vaccine when compared to MenACWY vaccine, in participants without a previous MenACWY vaccination (unprimed), is measured in terms of percentage of participants, achieving a 4-fold rise in hSBA titers against N. meningitidis 4 serogroups (A, C, W, Y). The calculation is based on Clopper Pearson method. Four-fold rise is defined as: If the pre-vaccination hSBA titer is < 4, then post-vaccination hSBA titer should be ≥ 16 . If the pre-vaccination hSBA titer is ≥ limit of detection (LOD) but < LL of quantification (LLOQ), then post-vaccination hSBA titer should be ≥ 4 times the LLOQ. If the pre-vaccination hSBA titer is ≥ LLOQ, then post-vaccination hSBA titer should be ≥ 4 times the pre-vaccination hSBA titer | At 1 month after vaccination schedule (i.e., Day 211 for the ABCWY Group [pooled lots] and Day 31 for the ACWY Group) | 
| Percentage of samples without bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the last MenABCWY dose (ABCWY group-pooled lots) and MenACWY vaccine (for ACWY group) | The effectiveness (test-based) of 2 doses of MenABCWY vaccine when compared to 1 dose of MenACWY vaccine, against a panel of N. meningitidis serogroup B strains is measured in terms of percentage of samples without bactericidal activity using enc-hSBA, which provides a qualitative assessment (yes/no) of the presence of sufficient bactericidal antibodies in human sera to kill a meningococcal strain at a specific dilution of 1:4. The percentages of samples are averaged across all 110 strains. | At 1 month after the vaccination schedule (i.e., at Day 211 for the ABCWY group [pooled lots] and Day 31 for the ACWY group) | 
| Percentage of samples with bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the last MenABCWY dose (pooled lots) and after 3-dose or 2-dose vaccination series of rMenB+OMV | The effectiveness of the MenABCWY vaccine (0,6-M schedule) when compared to the rMenB+OMV NZ vaccine (0,2,6-M or 0,6-M or 0,2-M) is measured in terms of percentage of samples with bactericidal activity using enc-hSBA, which provides a qualitative assessment (yes/no) of the presence of sufficient bactericidal antibodies in human sera to kill a meningococcal strain at a specific dilution of 1:4. The percentages of samples are averaged across all 110 strains. | At 1 month after the vaccination schedule (i.e., at Day 211 for the ABCWY Group [pooled lots], MenB_0_2_6 Group [3-dose schedule], MenB_0_6 Group and at Day 91 for the MenB_0_2_6 Group [2-dose schedule]) | 
| Percentage of participants whose sera kill ≥70% of the strains tested using enc-hSBA at 1 month after the last vaccination in the ABCWY Group (pooled lots) | The effectiveness (responder-based) of the MenABCWY vaccine is measured in terms of percentage of participants whose sera kill ≥70% of the strains tested using enc-hSBA, being calculated based on Clopper Pearson method. | At Day 211 | 
| Percentage of participants with any solicited local adverse events (AEs) | An adverse event is any untoward medical occurrence in a patient or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Solicited local adverse events to be assessed include injection site pain, erythema, swelling, induration. | During the 7 days (including the day of vaccination) after each vaccination (vaccines administered on Day 1, Day 61 and Day 181) | 
| Percentage of participants with any solicited systemic AEs | Solicited systemic AEs to be assessed include fever [temperature ≥ 38.0°C], nausea, fatigue, myalgia, arthralgia, headache. | During the 7 days (including the day of vaccination) after each vaccination (vaccines administered on Day 1, Day 61 and Day 181) | 
| Percentage of participants with any unsolicited AEs, Serious Adverse Events (SAEs), AEs leading to withdrawal, AE of special interest (AESIs) and medically attended AEs | Unsolicited AEs are defined as any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited AE. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect in the offspring of a study subject. AESIs are predefined (serious or non-serious) AEs 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 characterise and understand it. Medically attended AEs are symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider. | During the 30 days (including the day of vaccination) after each vaccination (vaccines administered on Day 1, Day 61 and Day 181) | 
| Percentage of participants with SAEs, AEs leading to withdrawal, AESIs and medically attended AEs | A SAEs is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect in the offspring of a study subject. AESIs are predefined (serious or non-serious) AEs 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 to characterize and understand it. Medically attended AEs are symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider. | Throughout the study period (Day 1 to Day 361) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with 4-fold rise in hSBA titers against N.meningitidis group B strains at 1 month after last MenABCWY dose(ABCWY group-pooled lots)and 1 month after 3-dose or 2-dose series of rMenB+OMV NZ in MenB groups, relative to baseline | The immunogenicity of MenABCWY vaccine at 1 month after the last dose when compared to 1 month after last dose of rMenB+OMV NZ vaccine according to 3 dose (0,2,6-M) or 2 dose (0,6-M and 0,2-M) schedule is measured in terms of percentage of participants achieving a 4-fold rise in hSBA titers against N. meningitidis serogroup B indicator strains (M14459, 96217, M13520 and NZ98/254 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively). The calculation is based on Clopper Pearson method. Four-fold rise per each indicator strain is defined as:- If the pre-vaccination hSBA titer is < 4, then post-vaccination* hSBA titer should be ≥ 16. - If the pre-vaccination hSBA titer is ≥ LOD and < LLOQ, then post-vaccination* hSBA titer should be ≥ 4 times the LLOQ. - If the pre-vaccination hSBA titer is ≥ LLOQ, then post-vaccination* hSBA titer should be ≥ 4 times the pre-vaccination hSBA titer. * post-second vaccination for 0,6 and 0,2 schedule and post-third vaccination for 0,2,6 schedule | At 1 month after the vaccination schedule (i.e., at Day 211 for the ABCWY Group [pooled lots], MenB_0_2_6 Group [3-dose schedule] and MenB_0_6 Group and at Day 91 for the MenB_0_2_6 Group [2-dose schedule]) | 
| Percentage of samples without bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after vaccination schedule in all groups | The effectiveness of the 3 dose (0,2,6-M) and 2 dose (0,6-M and 0,2-M) schedule of rMenB+OMV NZ vaccine and 2 doses of MenABCWY vaccine when compared to 1 month after the MenACWY vaccination (Day 31), against a panel of N. meningitidis serogroup B strains is measured in terms of percentage of samples without bactericidal activity using enc-hSBA, which provides a qualitative assessment (yes/no) of the presence of sufficient bactericidal antibodies in human sera to kill a meningococcal strain at a specific dilution of 1:4. The percentages of samples are averaged across all 110 strains. | At 1 month after the vaccination schedule (i.e., Day 211 for the MenB_0_2_6 group [3 dose schedule], MenB_0_6 group, ABCWY group [pooled lots], Day 91 for the MenB_0_2_6 group [2 dose schedule] and Day 31 for the MenACWY group) | 
| Percentage of participants classified by percentage of serogroup B invasive disease strains killed using enc-hSBA in each subject at 1 month after the 3-dose and 2-dose vaccination series of rMenB+OMV NZ and 1 month after last MenABCWY vaccine | The percentage of participants are classified by percentage of N.meningitidis serogroup B invasive strains killed using enc-hSBA and the corresponding 2- sided 95% CI based on Clopper-Pearson method is calculated for each vaccine group. The percentage of participants are averaged across 110 strains. | At 1 month after the vaccination schedule (i.e., Day 211 for MenB_0_2_6 group (3 dose schedule), MenB_0_6 group, ABCWY group (pooled lots), and Day 91 for MenB_0_2_6 group (2 dose schedule) | 
| Percentage of participants with hSBA titers ≥ LLOQ for each and all serogroup B indicator strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months and 0,2-months) and last MenABCWY (0,6-months) | The immune response to rMenB+OMV NZ and MenABCWY vaccine is evaluated by measuring bactericidal activity against each (individual response) and all (composite response) N. meningitidis serogroup B indicator strains- M14459, 96217, NZ98/254 and M13520. | At Day 1 (pre-vaccination) and after 1 month after the vaccination schedule (i.e, Day 211 for MenB_0_2_6 group [3 dose schedule], MenB_0_6 group, ABCWY group [pooled lots] and Day 91 for MenB_0_2_6 group [2 dose schedule]) | 
| Percentage of participants with 4-fold rise in hSBA titers for each of the serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months and 0,2-months) and MenABCWY (0,6-months), relative to baseline | The immune response to 3 dose (0,2,6-M) and 2 dose (0,6-M and 0,2-M) schedule of rMenB+OMV NZ and 2 doses of MenABCWY vaccine is evaluated by measuring bactericidal activity against each of the N. meningitidis serogroup B test strains- M14459, 96217, NZ98/254 and M13520 compared to baseline (Day 1). Four-fold rise per each indicator strain is defined as: - If the pre-vaccination hSBA titer is < 4, then post-vaccination* hSBA titer should be ≥ 16. - If the pre-vaccination hSBA titer is ≥ LOD and < LLOQ, then post-vaccination* hSBA titer should be ≥ 4 times the LLOQ. - If the pre-vaccination hSBA titer is ≥ LLOQ, then post-vaccination* hSBA titer should be ≥ 4 times the pre-vaccination hSBA titer. * post-2nd vaccination for 0,6 and 0,2 schedule and post-3rd vaccination for 0,2,6 schedule | At Day 1 (pre-vaccination) and at 1 month after the vaccination schedule (i.e, Day 211 for MenB_0_2_6 group [3-dose schedule], MenB_0_6 group, ABCWY group (pooled lots) and Day 91 for MenB_0_2_6 group [2 dose schedule]) | 
| hSBA GMTs against each of the N. meningitidis serogroup B strains at baseline and at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months and 0,2-months) and MenABCWY (0,6-months) | The immune response to rMenB+OMV NZ and MenABCWY vaccine is evaluated by measuring bactericidal activity against N. meningitidis serogroup B test strains in terms of GMTs after vaccination compared to baseline (Day 1). For each N. meningitidis serogroup B test strain (M14459, M13520, 96217 and NZ98/254), The GMTs (After vaccination/baseline) are calculated, with their associated 2-sided 95% CIs. | At Day 1 (pre-vaccination) and at 1 month after the vaccination schedule (i.e, Day 211 for MenB_0_2_6 group [3 dose schedule], MenB_0_6 group, ABCWY group [pooled lots] and Day 91 for MenB_0_2_6 group [2 dose schedule]) | 
| Geometric Mean Ratios (GMRs) for each of the N. meningitidis serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months and 0,2-months) and MenABCWY (0,6-months), relative to baseline | The immune response to rMenB+OMV NZ and MenABCWY vaccine is evaluated by measuring bactericidal activity against N. meningitidis serogroup B test strains after vaccination compared to baseline (Day 1). For each N. meningitidis serogroup B test strain (M14459, M13520, 96217 and NZ98/254), the GMRs (after vaccination/baseline) are calculated, with their associated 2-sided 95% CIs | At 1 month after the vaccination schedule (i.e, Day 211 for MenB_0_2_6 group [3 dose schedule], MenB_0_6 group, ABCWY group [pooled lots] and Day 91 for MenB_0_2_6 group [2 dose schedule]) versus Day 1 | 
| Percentage of participants with hSBA titers ≥ LLOQ for each of the N. meningitidis groups A,C,W,Y at Day 1,1 month after the first and after the last MenABCWY vaccination for ABCWY group (pooled lots) and 1 month after the MenACWY vaccine for ACWY group | The immune responses to MenABCWY and MenACWY vaccines are evaluated by measuring bactericidal activity against N. meningitidis serogroups A, C, W and Y after vaccination compared to baseline (Day 1) and expressed as the percentage of participants with hSBA titers ≥ LLOQ for serogroups A, C, W and Y at baseline and 1 month after vaccination schedule of MenABCWY and MenACWY vaccines. The corresponding 2- sided 95% CI based on Clopper-Pearson method is calculated for each vaccine group. | At Day 1, and 1 month after vaccination schedule (i.e, at Day 31 for ABCWY group [pooled lots -first dose] and for ACWY Group, and at Day 211 for ABCWY group [pooled lots - second dose]) | 
| Percentage of participants with 4-fold rise in hSBA titers for each of the N. meningitidis serogroups A, C, W and Y at 1 month after the first MenABCWY dose for the ABCWY Group (pooled lots) and 1 month after the MenACWY vaccine for ACWY Group | The immune response to MenABCWY vaccine compared to MenACWY vaccine is evaluated by measuring bactericidal activity against each of the N. meningitidis serogroups A, C, W and Y at Day 31 compared to baseline (Day 1). Four-fold rise is defined as: - If the pre-vaccination hSBA titer is < 4, then post-vaccination hSBA titer should be ≥ 16. - If the pre-vaccination hSBA titer is ≥ LOD but < LLOQ, then post-vaccination hSBA titer should be ≥ 4 times the LLOQ. - If the pre-vaccination hSBA titer is ≥ LLOQ, then post-vaccination hSBA titer should be ≥ 4 times the pre-vaccination hSBA titer. The corresponding 2- sided 95% CI based on Clopper-Pearson method is calculated for each vaccine group. | At Day 1 and Day 31 | 
| hSBA GMTs against each of the N. meningitidis serogroups A, C, W and Y at Day 1 and 1 month after the first and after the last MenABCWY vaccination for the ABCWY Group (pooled lots) and 1 month after the MenACWY vaccination for ACWY Group | The immune responses to MenABCWY and MenACWY vaccines are evaluated by measuring bactericidal activity against N. meningitidis serogroups A, C, W and Y in terms of GMTs after vaccination compared to baseline (Day 1). For each N. meningitidis serogroups A, C, W and Y, the GMTs (after vaccination/baseline) are calculated, with their associated 2-sided 95% CIs. | At Day 1, and 1 month after vaccination schedule (i.e, at Day 31 for ABCWY group [pooled lots -first dose] and for ACWY Group, and at Day 211 for ABCWY group [pooled lots - second dose]) | 
| GMRs for each of the N. meningitidis serogroups A, C, W and Y at 1 month after the first and after the last MenABCWY vaccination for the ABCWY Group (pooled lots) and 1 month after the MenACWY vaccination for ACWY Group | The immune responses to MenABCWY and MenACWY vaccines are evaluated by measuring bactericidal activity against N. meningitidis serogroups A, C, W and Y at Day 31 compared to baseline (Day 1). For each N. meningitidis serogroups A, C, W and Y, the GMRs (after vaccination/baseline) are calculated, with their associated 2-sided 95% CIs. | At 1 month after vaccination schedule (i.e, at Day 31 for ABCWY group [pooled lots -first dose] and for ACWY Group, and at Day 211 for ABCWY group [pooled lots - second dose]) versus baseline (Day 1) | 
| Immunoglobulin G (IgG) antibodies against N. meningitidis serogroups A, C, W and Y at Day 1 and 1 month after the first and after the last MenABCWY vaccination for ABCWY Group (pooled lots) and 1 month after the MenACWY vaccination for ACWY Group | The immune responses to MenABCWY and MenACWY vaccines are evaluated by measuring the total IgG in terms of enzyme-linked immunosorbent assay (ELISA) geometric mean concentrations (GMCs) after vaccination compared to baseline (Day 1). | At Day 1, and 1 month after vaccination schedule (i.e, at Day 31 for ABCWY group [pooled lots -first dose] and for ACWY Group, and at Day 211 for ABCWY group [pooled lots - second dose]) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bexsero, Menveo, MenABCWY, Effectiveness, Invasive meningococcal disease, Meningitis