A Study on the Safety, Effectiveness and Immune Response of Meningococcal Combined ABCWY Vaccine in Healthy Adolescents and Adults

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, effectiveness and immune response of the meningococcal combined ABCWY vaccine (GSK4023393A) intended to protect against invasive meningococcal disease (IMD) caused by all 5 meningococcal serogroups. The first time-in-human (FTIH), Phase I part of this study will be conducted in healthy adults in a dose-escalating fashion with 2 formulations of the investigational MenABCWY-2Gen vaccine and will serve as a safety lead-in to the Phase II study. The Phase II part of the study will be conducted in 2 parts: The 'formulation and schedule-finding' part will follow in healthy adolescents and young adults and it is designed to select the vaccine formulation and the schedule to be tested in Phase III. The 'blood sourcing' part will be conducted in healthy adults in order to collect sufficient serum samples for the development of assays to be used in the MenABCWY-2Gen vaccine clinical development program.

Official Title
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A Phase I/II, Randomised, Controlled Study to Assess the Safety, Effectiveness and Immune Response of Meningococcal Combined ABCWY Vaccine When Administered to Healthy Adults (Phase I) and to Healthy Adolescents and Adults (Phase II)

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Combination Product: MenABCWY-2Gen low dose vaccine
* Combination Product: MenABCWY-2Gen high dose vaccine
* Combination Product: Placebo
* Combination Product: MenB vaccine
* Biological: MenACWY vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All inclusion criteria are applicable for both study phases, except where specified otherwise. Participants and/or participants' parent(s)/Legally Acceptable Representative(s) (LAR) who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the eDiaries, return for follow-up visits). Written or witnessed/thumb printed informed consent obtained from the participant or /parent(s)/LAR(s) of the participant prior to performance of any study specific procedure. Written informed assent obtained from the participant (if applicable) prior to performing any study specific procedure. Phase I only: A male or female between, and including, 18 and 40 years of age (i.e. 40 years + 364 days) at the time of the first study intervention administration. Phase II (Formulation and Schedule-finding) only: 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 study intervention administration. Phase II (Sourcing) only: A male or female between, and including, 18 and 50 years of age (i.e. 50 years + 364 days) at the time of the first study intervention administration. Participants 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). Healthy participants as established by medical history and clinical examination before entering into the study. Female participants 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 participants of childbearing potential may be enrolled in the study, if the participant: has practiced adequate contraception for 1 month prior to study intervention administration, and has a negative pregnancy test on the day of study intervention administration, and has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the study intervention administration. 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. Are obese at enrolment (e.g. for participants from 20 years of age a body mass index (BMI) ≥ 30 kg/m2, for participants up to 19 years of age a BMI ≥ 95th percentile for age and gender or as applicable per country recommendations). Any neuroinflammatory (including but not limited to: demyelinating disorders, encephalitis or myelitis of any origin), congenital neurological conditions, encephalopathies, seizures (including all subtypes such as: absence seizures, generalised tonic-clonic seizures, partial complex seizures, partial simple 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 study interventions. Hypersensitivity, including allergy, to any component of vaccines, including diphtheria toxoid (CRM197) 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 (including, but not limited to: blood, endocrine, hepatic, muscular, nervous system or skin autoimmune disorders; lupus erythematosus and associated conditions; rheumatoid arthritis and associated conditions; scleroderma and associated disorders) or immunodeficiency syndromes (including, but not limited to: acquired immunodeficiency syndromes and primary immunodeficiency syndromes). Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 3 months prior to study vaccination until the last blood sampling visit for Phase I and Phase II (Sourcing) and Visit 5 (Day 211) for Phase II (Formulation and Schedule-finding). This will mean prednisone equivalent ≥20 mg/day for adult participants/ ≥0.5 mg/kg/day with maximum of 20 mg/day for paediatric participants. 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 other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. Prior/Concomitant therapy Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) (Day -29 to Day 1), or their 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 3 months before the administration of the first dose of study intervention(s) or planned administration until the last blood sampling visit for Phase I and Phase II (Sourcing) and Visit 5 (Day 211) for Phase II (Formulation and Schedule-finding). Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first study intervention dose(s) until the last blood sampling visit for Phase I and Phase II (Sourcing) and Visit 5 (Day 211) for Phase II (Formulation and Schedule-finding). For corticosteroids, this will mean prednisone equivalent ≥20 mg/day for adult participants/ ≥0.5 mg/kg/day with maximum of 20 mg/day for paediatric participants. 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 participant has been or will be exposed to an investigational or a non-investigational intervention (drug/invasive medical device). Other exclusions 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 dependents, family, or household member. Phase II (Formulation and Schedule-finding): Child in care.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 50 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
Interventional Model Description: The Phase I safety lead-in will follow a staggered enrolment Phase II will start only after a positive outcome from the internal Safety Review Committee (iSRC) review of the safety data from participants receiving vaccination in Phase I of the study.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABCWY low dose Group<br>Participants receive MenABCWY-2Gen low dose vaccine and are followed up until Day 211 in study Phase I. | Combination Product: MenABCWY-2Gen low dose vaccine<br>* MenABCWY-2Gen low dose vaccine is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the ABCWY low dose Group in study Phase I, ABCWY low dose_06 Group and ABCWY low dose_02 Group in study Phase II (Formulation and Schedule-finding) and as 2 doses to participants in the ABCWY low dose_01 Group, ABCWY low doseS_02 Group and ABCWY low doseS_06 Group in study Phase II (Sourcing).<br>|
| Placebo Comparator: Placebo low dose Group<br>Participants receive NaCl as a control for ABCWY low dose group and are followed up until Day 211 in study Phase I. | Combination Product: Placebo<br>* Placebo is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the Placebo low dose Group, Placebo high dose Group in study Phase I and as 1 dose to participants in the ABCWY low dose_06 Group, ABCWY low dose_02 Group, ABCWY high dose_06 Group, ABCWY high dose_02 Group in study Phase II (Formulation and Schedule-finding).<br>* Other names: NaCl, saline solution;|
| Experimental: ABCWY high dose Group<br>Participants receive MenABCWY-2Gen high dose vaccine and are followed up until Day 211 in study Phase I. | Combination Product: MenABCWY-2Gen high dose vaccine<br>* MenABCWY-2Gen high dose vaccine is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the ABCWY high dose Group in study Phase I, ABCWY high dose_06 Group and ABCWY high dose_02 Group in study Phase II (Formulation and Schedule-finding) and as 2 doses to participants in the ABCWY high dose_01 Group, ABCWY high doseS_02 Group and ABCWY high doseS_06 Group in study Phase II (Sourcing).<br>|
| Placebo Comparator: Placebo high dose Group<br>Participants receive NaCl as a control for ABCWY high dose group and are followed up until Day 211 in study Phase I. | Combination Product: Placebo<br>* Placebo is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the Placebo low dose Group, Placebo high dose Group in study Phase I and as 1 dose to participants in the ABCWY low dose_06 Group, ABCWY low dose_02 Group, ABCWY high dose_06 Group, ABCWY high dose_02 Group in study Phase II (Formulation and Schedule-finding).<br>* Other names: NaCl, saline solution;|
| Experimental: ABCWY low dose_06 Group<br>Participants receive MenABCWY-2Gen low dose vaccine in a 0, 6 month schedule and 1 dose of NaCl and are followed up until Day 541 in study Phase II (Formulation and Schedule-finding). | Combination Product: MenABCWY-2Gen low dose vaccine<br>* MenABCWY-2Gen low dose vaccine is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the ABCWY low dose Group in study Phase I, ABCWY low dose_06 Group and ABCWY low dose_02 Group in study Phase II (Formulation and Schedule-finding) and as 2 doses to participants in the ABCWY low dose_01 Group, ABCWY low doseS_02 Group and ABCWY low doseS_06 Group in study Phase II (Sourcing).<br>Combination Product: Placebo<br>* Placebo is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the Placebo low dose Group, Placebo high dose Group in study Phase I and as 1 dose to participants in the ABCWY low dose_06 Group, ABCWY low dose_02 Group, ABCWY high dose_06 Group, ABCWY high dose_02 Group in study Phase II (Formulation and Schedule-finding).<br>* Other names: NaCl, saline solution;|
| Experimental: ABCWY low dose_02 Group<br>Participants receive MenABCWY-2Gen low dose vaccine in a 0, 2 month schedule and 1 dose of NaCl and are followed up until Day 541 in study Phase II (Formulation and Schedule-finding). | Combination Product: MenABCWY-2Gen low dose vaccine<br>* MenABCWY-2Gen low dose vaccine is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the ABCWY low dose Group in study Phase I, ABCWY low dose_06 Group and ABCWY low dose_02 Group in study Phase II (Formulation and Schedule-finding) and as 2 doses to participants in the ABCWY low dose_01 Group, ABCWY low doseS_02 Group and ABCWY low doseS_06 Group in study Phase II (Sourcing).<br>Combination Product: Placebo<br>* Placebo is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the Placebo low dose Group, Placebo high dose Group in study Phase I and as 1 dose to participants in the ABCWY low dose_06 Group, ABCWY low dose_02 Group, ABCWY high dose_06 Group, ABCWY high dose_02 Group in study Phase II (Formulation and Schedule-finding).<br>* Other names: NaCl, saline solution;|
| Experimental: ABCWY high dose_06 Group<br>Participants receive MenABCWY-2Gen high dose vaccine in a 0, 6 month schedule and 1 dose of NaCl and are followed up until Day 541 in study Phase II (Formulation and Schedule-finding). | Combination Product: MenABCWY-2Gen high dose vaccine<br>* MenABCWY-2Gen high dose vaccine is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the ABCWY high dose Group in study Phase I, ABCWY high dose_06 Group and ABCWY high dose_02 Group in study Phase II (Formulation and Schedule-finding) and as 2 doses to participants in the ABCWY high dose_01 Group, ABCWY high doseS_02 Group and ABCWY high doseS_06 Group in study Phase II (Sourcing).<br>Combination Product: Placebo<br>* Placebo is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the Placebo low dose Group, Placebo high dose Group in study Phase I and as 1 dose to participants in the ABCWY low dose_06 Group, ABCWY low dose_02 Group, ABCWY high dose_06 Group, ABCWY high dose_02 Group in study Phase II (Formulation and Schedule-finding).<br>* Other names: NaCl, saline solution;|
| Experimental: ABCWY high dose_02 Group<br>Participants receive MenABCWY-2Gen high dose vaccine in a 0,2 month schedule and 1 dose of NaCl and are followed up until Day 541 in study Phase II (Formulation and Schedule-finding). | Combination Product: MenABCWY-2Gen high dose vaccine<br>* MenABCWY-2Gen high dose vaccine is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the ABCWY high dose Group in study Phase I, ABCWY high dose_06 Group and ABCWY high dose_02 Group in study Phase II (Formulation and Schedule-finding) and as 2 doses to participants in the ABCWY high dose_01 Group, ABCWY high doseS_02 Group and ABCWY high doseS_06 Group in study Phase II (Sourcing).<br>Combination Product: Placebo<br>* Placebo is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the Placebo low dose Group, Placebo high dose Group in study Phase I and as 1 dose to participants in the ABCWY low dose_06 Group, ABCWY low dose_02 Group, ABCWY high dose_06 Group, ABCWY high dose_02 Group in study Phase II (Formulation and Schedule-finding).<br>* Other names: NaCl, saline solution;|
| Active Comparator: Control Group<br>Participants randomized to Control Group receive 2 doses of Bexsero (MenB) vaccine and 1 dose of Menveo (MenACWY), 1 dose of NaCl and are followed up until Day 541 in study Phase II (Formulation and Schedule-finding). | Combination Product: MenB vaccine<br>* MenB vaccine is administered intramuscularly in the deltoid region of the non-dominant arm, whenever it's possible, as 2 doses in a 0,6-months schedule to participants in the Control Group in study Phase II (Formulation and Schedule-finding).<br>* Other names: GSK's meningococcal group B vaccine, Bexsero;Biological: MenACWY vaccine<br>* MenACWY vaccine is administered intramuscularly in the deltoid region of the dominant arm as 1 dose to participants in the Control Group in study Phase II (Formulation and Schedule-finding).<br>* Other names: GSK's combined meningococcal groups A, C, Y and W-135 conjugate vaccine, Menveo;|
| Experimental: ABCWY low dose_01 Group<br>Participants receive MenABCWY-2Gen low dose vaccine in a 0,1 month schedule and are followed up until Day 211 in study Phase II (Sourcing). | Combination Product: MenABCWY-2Gen low dose vaccine<br>* MenABCWY-2Gen low dose vaccine is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the ABCWY low dose Group in study Phase I, ABCWY low dose_06 Group and ABCWY low dose_02 Group in study Phase II (Formulation and Schedule-finding) and as 2 doses to participants in the ABCWY low dose_01 Group, ABCWY low doseS_02 Group and ABCWY low doseS_06 Group in study Phase II (Sourcing).<br>|
| Experimental: ABCWY high dose_01 Group<br>Participants receive MenABCWY-2Gen high dose vaccine in a 0,1 month schedule and are followed up until Day 211 in study Phase II (Sourcing). | Combination Product: MenABCWY-2Gen high dose vaccine<br>* MenABCWY-2Gen high dose vaccine is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the ABCWY high dose Group in study Phase I, ABCWY high dose_06 Group and ABCWY high dose_02 Group in study Phase II (Formulation and Schedule-finding) and as 2 doses to participants in the ABCWY high dose_01 Group, ABCWY high doseS_02 Group and ABCWY high doseS_06 Group in study Phase II (Sourcing).<br>|
| Experimental: ABCWY low doseS_02 Group<br>Participants receive MenABCWY-2Gen low dose vaccine in a 0, 2 month schedule and are followed up until Day 241 in study Phase II (Sourcing). | Combination Product: MenABCWY-2Gen low dose vaccine<br>* MenABCWY-2Gen low dose vaccine is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the ABCWY low dose Group in study Phase I, ABCWY low dose_06 Group and ABCWY low dose_02 Group in study Phase II (Formulation and Schedule-finding) and as 2 doses to participants in the ABCWY low dose_01 Group, ABCWY low doseS_02 Group and ABCWY low doseS_06 Group in study Phase II (Sourcing).<br>|
| Experimental: ABCWY high doseS_02 Group<br>Participants receive MenABCWY-2Gen high dose vaccine in a 0, 2 month schedule and are followed up until Day 241 in study Phase II (Sourcing). | Combination Product: MenABCWY-2Gen high dose vaccine<br>* MenABCWY-2Gen high dose vaccine is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the ABCWY high dose Group in study Phase I, ABCWY high dose_06 Group and ABCWY high dose_02 Group in study Phase II (Formulation and Schedule-finding) and as 2 doses to participants in the ABCWY high dose_01 Group, ABCWY high doseS_02 Group and ABCWY high doseS_06 Group in study Phase II (Sourcing).<br>|
| Experimental: ABCWY low doseS_06 Group<br>Participants receive MenABCWY-2Gen low dose vaccine in a 0, 6 month schedule and are followed up until Day 361 in study Phase II (Sourcing). | Combination Product: MenABCWY-2Gen low dose vaccine<br>* MenABCWY-2Gen low dose vaccine is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the ABCWY low dose Group in study Phase I, ABCWY low dose_06 Group and ABCWY low dose_02 Group in study Phase II (Formulation and Schedule-finding) and as 2 doses to participants in the ABCWY low dose_01 Group, ABCWY low doseS_02 Group and ABCWY low doseS_06 Group in study Phase II (Sourcing).<br>|
| Experimental: ABCWY high doseS_06 Group<br>Participants receive MenABCWY-2Gen high dose vaccine in a 0, 6 month schedule and are followed up until Day 361 in study Phase II (Sourcing). | Combination Product: MenABCWY-2Gen high dose vaccine<br>* MenABCWY-2Gen high dose vaccine is administered intramuscularly in the deltoid region of the non-dominant arm as 2 doses to participants in the ABCWY high dose Group in study Phase I, ABCWY high dose_06 Group and ABCWY high dose_02 Group in study Phase II (Formulation and Schedule-finding) and as 2 doses to participants in the ABCWY high dose_01 Group, ABCWY high doseS_02 Group and ABCWY high doseS_06 Group in study Phase II (Sourcing).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of participants with solicited administration site events in study Phase I (Safety Lead-in) | The solicited administration site events include injection site pain, erythema (redness), swelling and induration. Any erythema, swelling and induration are defined as a symptom with a surface diameter equal to or greater than 25 millimeters. | During the 7 days (including the day of vaccination) following vaccination at Day 1 | 
| Percentages of participants with solicited administration site events in study Phase I (Safety Lead-in) |  | During the 7 days (including the day of vaccination) following vaccination at Day 31 | 
| Percentages of participants with solicited systemic events in study Phase I (Safety Lead-in) | The solicited systemic events include fever (temperature ≥ 38.0°C), nausea, fatigue, myalgia, arthralgia and headache. | During the 7 days (including the day of vaccination) following vaccination at Day 1 | 
| Percentages of participants with solicited systemic events in study Phase I (Safety Lead-in) |  | During the 7 days (including the day of vaccination) following vaccination at Day 31 | 
| Percentages of participants with any unsolicited adverse events (AEs), including all serious adverse events (SAEs), AEs leading to withdrawal and AEs of special interest (AESIs) in study Phase I (Safety Lead-in) | The unsolicited AEs includes 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 is reported as an unsolicited adverse event. Any occurrence of the event regardless of the intensity grade. 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. | During the 30 days (including the day of vaccination) following vaccination at Day 1 | 
| Percentages of participants with any unsolicited adverse events (AEs), including all serious adverse events (SAEs), AEs leading to withdrawal and AEs of special interest (AESIs) in study Phase I (Safety Lead-in) |  | During the 30 days (including the day of vaccination) following vaccination at Day 31 | 
| Percentages of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase I (Safety Lead-in) | 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. | Throughout the study period (Day 1 through Day 211) | 
| Percentages of participants with haematological and biochemical laboratory abnormalities, and changes from the baseline values, in study Phase I (Safety Lead-in) | Haematology and biochemistry assays for safety assessment are performed in all participants in Phase I, in the investigator's laboratory using standard procedures as per local practice. | At Day 8 after the first vaccination | 
| Percentages of samples with bactericidal serum activity against a panel of 110 randomly selected endemic US N. meningitidis serogroup B invasive disease strains in study Phase II (Formulation and Schedule-finding) | The effectiveness of the MenABCWY-2Gen (low and high dose) vaccine when administered at 0,2- or 0,6-months schedule compared to MenB vaccine administered at 0,6-months schedule, against a panel of 110 randomly selected endemic N. meningitidis serogroup B strains is measured in terms of percentage of samples with 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. | At Day 211 (1 month after the last vaccination) | 
| Percentages of participants with a 4-fold rise in hSBA titers against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding) | The immune response to the MenABCWY-2Gen (low and high dose) vaccine when administered at 0,2- or 0,6-months schedule compared to MenACWY vaccine (single dose), relative to day 1 in the ABCWY and control groups (0, 6 month schedule) and day 31 in ABCWY (0, 2 month schedule) is measured in terms of percentage of participants achieving a 4-fold rise in hSBA titers against serogroups A, C, W and Y. The 4-fold rise is defined as: -a post-vaccination hSBA titer ≥ 16 for participants with a pre-vaccination hSBA titer < 4, -a post-vaccination hSBA titer ≥ 4 times the lower limit of quantitation (LLOQ) for participants with a pre-vaccination hSBA titer ≥LOD but <LLOQ, and. -a post-vaccination hSBA titer ≥ 4 times the pre-vaccination hSBA titer for participants with a pre-vaccination hSBA titer ≥LLOQ. | At 1 month after the vaccination schedule (i.e., Day 211 for the ABCWY groups and at Day 31 the Control group) | 
| Percentages of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) | The solicited administration site events include injection site pain, erythema (redness), swelling and induration. Any erythema, swelling and induration are defined as a symptom with a surface diameter equal to or greater than 25 millimeters. | During the 7 days (including the day of vaccination) following vaccination at Day 1 | 
| Percentages of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) |  | During the 7 days (including the day of vaccination) following vaccination at Day 121 | 
| Percentages of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) |  | During the 7 days (including the day of vaccination) following vaccination at Day 181 | 
| Percentages of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) | The solicited systemic events include fever (temperature ≥ 38.0°C), nausea, fatigue, myalgia, arthralgia and headache. | During the 7 days (including the day of vaccination) following vaccination at Day 1 | 
| Percentages of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) |  | During the 7 days (including the day of vaccination) following vaccination at Day 121 | 
| Percentages of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) |  | During the 7 days (including the day of vaccination) following vaccination at Day 181 | 
| Percentages of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) | The unsolicited AEs includes 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 are reported as an unsolicited adverse event. Any occurrence of the event regardless of the intensity grade. 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. | During the 30 days (including the day of vaccination) following vaccination at Day 1 | 
| Percentages of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) |  | During the 30 days (including the day of vaccination) following vaccination at Day 121 | 
| Percentages of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) |  | During the 30 days (including the day of vaccination) following vaccination at Day 181 | 
| Percentages of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Formulation and Schedule-Finding) | 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. | Throughout the study period (Day 1 through Day 541) | 
| Percentages of participants with solicited administration site events in study Phase II (Sourcing) | The solicited administration site events include injection site pain, erythema (redness), swelling and induration. Any erythema, swelling and induration are defined as a symptom with a surface diameter equal to or greater than 25 millimeters. | During the 7 days (including the day of vaccination) following vaccination at Day 1 | 
| Percentages of participants with solicited administration site events in study Phase II (Sourcing) |  | During the 7 days (including the day of vaccination) following vaccination at Day 31 | 
| Percentages of participants with solicited administration site events in study Phase II (Sourcing) |  | During the 7 days (including the day of vaccination) following vaccination at Day 61 | 
| Percentages of participants with solicited administration site events in study Phase II (Sourcing) |  | During the 7 days (including the day of vaccination) following vaccination at Day 181 | 
| Percentages of participants with solicited systemic events in study Phase II (Sourcing) | The solicited systemic events include fever (temperature ≥ 38.0°C), nausea, fatigue, myalgia, arthralgia and headache. | During the 7 days (including the day of vaccination) following vaccination at Day 1 | 
| Percentages of participants with solicited systemic events in study Phase II (Sourcing) |  | During the 7 days (including the day of vaccination) following vaccination at Day 31 | 
| Percentages of participants with solicited systemic events in study Phase II (Sourcing) |  | During the 7 days (including the day of vaccination) following vaccination at Day 61 | 
| Percentages of participants with solicited systemic events in study Phase II (Sourcing) |  | During the 7 days (including the day of vaccination) following vaccination at Day 181 | 
| Percentages of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) | The unsolicited AEs includes 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 is reported as an unsolicited adverse event. Any occurrence of the event regardless of the intensity grade. 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. | During the 30 days (including the day of vaccination) following vaccination at Day 1 | 
| Percentages of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) |  | During the 30 days (including the day of vaccination) following vaccination at Day 31 | 
| Percentages of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) |  | During the 30 days (including the day of vaccination) following vaccination at Day 61 | 
| Percentages of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) |  | During the 30 days (including the day of vaccination) following vaccination at Day 181 | 
| Percentages of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Sourcing) | 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. | Throughout the study period (Day 1 through Day 211) | 
| Percentages of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Sourcing) |  | Throughout the study period (Day 1 through Day 241) | 
| Percentages of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Sourcing) |  | Throughout the study period (Day 1 through Day 361) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of serogroup B invasive disease strains killed in each participant sample in study Phase II (Formulation and Schedule-finding) | The percentages of strains killed measured by enc-hSBA against a randomly selected panel of strains and the corresponding exact 2-sided 95% CIs based on Clopper-Pearson method is calculated in all groups at 1 month after the last vaccination of MenABCWY-2Gen (low and high dose) vaccine administered at 0,2 and 0,6-months schedule and of the MenB vaccine administered at 0,6-months schedule. | At Day 211 (1 month after the last vaccination) | 
| Percentages of participants with hSBA titers ≥LLOQ for each and all serogroup B indicator strains in study Phase II (Formulation and Schedule-finding) | The immune response to MenABCWY-2Gen (low and high dose) administered at 0,2 and 0,6-months schedule and MenB vaccine administered at 0,6-months schedule is evaluated by measuring bactericidal activity using a qualified AO hSBA against a standard panel of serogroup B indicator strains. | At Day 1 in ABCWY (0,6-months) and Control groups, Day 31 in ABCWY groups (0,2-months) and Day 211 in all study groups | 
| Percentages of participants with 4-fold rise in hSBA titers against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding) | The immune response to MenABCWY-2Gen (low and high dose) vaccine when administered at 0,2- or 0,6-months schedule and to MenB vaccine administered at 0,6-months schedule, relative to day 1 in ABCWY (0,6 month schedule) and control groups and day 31 in ABCWY (0,2 month schedule) is measured in terms of percentage of participants achieving a 4-fold rise in hSBA titers against serogroup B indicator strains. The calculation is based on Clopper Pearson method. The 4-fold rise is defined as: -a post-vaccination hSBA titer ≥ 16 for participants with a pre-vaccination hSBA titre < 4, -a post-vaccination hSBA titer ≥ 4 times the LLOQ for participants with a pre-vaccination hSBA titer ≥LOD but <LLOQ, and. -a post-vaccination hSBA titer ≥ 4 times the pre-vaccination hSBA titer for participants with a pre-vaccination hSBA titer ≥ LLOQ. | At Day 211 (1 month after the last vaccination) | 
| hSBA Geometric mean titers (GMTs) against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding) | The immune response to MenABCWY-2Gen (low and high dose) vaccine administered at 0,2 and 0,6-months schedule and to the MenB vaccine administered at 0,6-months schedule against serogroup B indicator strains is determined using hSBA GMTs.The hSBA titers are logarithmically transformed (base10) to fulfil the normal distribution assumption. For each B strains, the GMTs) are calculated with their associated 2-sided 95% CIs, by exponentiating the corresponding log-transformed means and their 95% CIs. | At Day 1 in ABCWY groups (0,6-months) and Control groups, Day 31 in ABCWY groups (0,2-months) and Day 211 in all study groups | 
| hSBA Geometric mean ratios (GMRs) against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding) | The immune response to the MenABCWY-2Gen (low and high dose) vaccine administered at 0,2 and 0,6-months schedule and to the MenB vaccine administered at 0,6-months schedule against serogroup B indicator strains is determined using hSBA GMRs. The hSBA titers are logarithmically transformed (base10) to fulfil the normal distribution assumption. For each B strains, the GMRs (post-vaccination/ Day 1 (Month 0)) are calculated with their associated 2-sided 95% CIs, by exponentiating the corresponding log-transformed means and their 95% CIs. | At Day 211 in all study groups versus Day 1 in ABCWY (0,6-months) and Control groups and Day 31 in ABCWY groups (0,2-months) | 
| Percentages of participants with hSBA titers ≥ LLOQ for serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding) | The immune response to MenABCWY-2Gen (low and high dose) vaccine administered at at 0,2 and 0,6-months schedule and MenACWY vaccine administered at 0,6-months schedule is evaluated against serogroups A, C, W and Y . The percentages of participants with hSBA titers ≥ LLOQ and the corresponding exact 2-sided 95% CIs based on Clopper-Pearson method are calculated. | At Day 1 in ABCWY (0,6-months) and Control groups, Day 31 in ABCWY groups (0,2- and 0,6-months), Day 211 (1 month after the last vaccination) in all ABCWY groups and Day 31 (1 month after the MenACWY vaccination) in Control group | 
| Percentages of participants with a 4-fold rise in hSBA titers against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding) | The immune response to the MenABCWY-2Gen (low and high dose) vaccine when administered at 0,6-months schedule, relative to day 1 is measured in terms of percentage of participants achieving a 4-fold rise in hSBA titers against serogroups A, C, W and Y. Serum bactericidal activity against MenACWY will be determined by using a validated AO hSBA. The 4-fold rise is defined as: -a post-vaccination hSBA titre ≥ 16 for participants with a pre-vaccination hSBA titre < 4, -a post-vaccination hSBA titre ≥ 4 times the LLOQ for participants with a pre-vaccination hSBA titre ≥ LOD but < LLOQ, and. -a post-vaccination hSBA titre ≥4 times the pre-vaccination hSBA titre for participants with a pre-vaccination hSBA titre ≥ LLOQ. | At Day 31 (1 month after the first MenABCWY-2Gen vaccination) | 
| hSBA GMTs against serogroups A, C, W and Y | The immune response to the MenABCWY-2Gen (low and high dose) vaccine (0,2- and 0,6-months schedule) and MenACWY vaccine (single dose) is evaluated by hSBA titers which are logarithmically transformed (base10) to fulfil the normal distribution assumption. For each serogroup A, C, W and Y, the GMTs are calculated with their associated 2-sided 95% CIs, by exponentiating the corresponding log-transformed means and their 95% CIs. | At Day 1 in ABCWY groups (0,6-months) and Control group, Day 31 in ABCWY groups (0,2-months and 0,6-moths), Day 211 in all ABCWY groups and Day 31 in the Control group | 
| hSBA GMRs against serogroups A, C, W and Y | The hSBA titers groups will be logarithmically transformed (base10) to fulfil the normal distribution assumption. For each serogroup A, C, W and Y, the GMRs (post-vaccination/ Day 1 (Month 0) are calculated with their associated 2-sided 95% CIs, by exponentiating the corresponding log-transformed means and their 95% CIs. | At Day 31 versus Day 1 in ABCWY (0,6-months) and Control groups, Day 211 versus Day 1 in ABCWY (0,6-months) groups and Day 211 versus Day 31 in ABCWY (0,2-months) groups | 
| Immunoglobulin G (IgG) antibodies against serogroups A, C, W and Y | The immune responses to MenABCWY-2Gen (low and high dose) and MenACWY vaccines are evaluated by measuring the total IgG in terms of electrochemiluminescence-based (ECL) multiplex assay Geometric Mean Concentrations (GMCs) | At Day 1 in ABCWY groups (0,6-months) and Control groups, Day 31 in ABCWY groups (0,2-months) and Day 31 in the ABCWY groups (0,6-months) and in Control group, and Day 211 for all ABCWY groups | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bexsero, Menveo, Boostrix, MenABCWY-2Gen, Effectiveness, Safety, Invasive Meningococcal Disease, Adolescents and Adults