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

Phase 3

Completed

• Conditions: Infections, Meningococcal
• Interventions: Combination Product: rMenB+OMV NZ vaccine; Combination Product: MenABCWY-1; Combination Product: MenABCWY-3; Biological: Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY); Combination Product: MenABCWY-2; Combination Product: Placebo

• Registration Number: NCT04502693
• Lead Sponsor: GlaxoSmithKline

Brief Summary

The purpose of this study was 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 were evaluated in the study.

Detailed Description

As per the feedback from the Center for Biologics Evaluation and Research (CBER), the scope of this post-marketing commitment study was 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 the MenB_0_2_6, MenB_0_6 group, and MenACWY group, respectively, at day 211 were only as part of the standard care of treatment and to maintain blinding. These vaccination schedules were not considered for any endpoint evaluations.

Study Timeline

• Study First Submitted: 2020-08-04
• Study First Submitted QC: 2020-08-04
• Study First Posted: 2020-08-06
• Study Start: 2020-08-14
• Primary Completion: 2022-09-13
• Study Completion: 2022-09-13
• Disposition First Submitted: 2023-09-04
• Results First Submitted: 2023-12-21
• Status Verified: 2024-02
• Results First Submitted QC: 2024-02-09
• Last Update Submitted: 2024-02-09
• Results First Posted: 2024-03-05
• Disposition First Posted: 2024-03-05
• Last Update Posted: 2024-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3657

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ABCWY-3 Group	MenABCWY-3	Participants received 2 doses of MenABCWY lot 3 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211.
MenB_0_2_6 Group	Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY)	Participants received 3 doses of rMenB+OMV NZ vaccine on Day 1, Day 61 and Day 181. Participants received 1 dose of MenACWY vaccine at Day 211 as a standard of care.
MenB_0_6 Group	rMenB+OMV NZ vaccine	Participants received 2 doses of rMenB+OMV NZ vaccine on Day 1, and Day 181, 1 dose of MenACWY vaccine on Day 61. Participants received 1 dose of Placebo on Day 211 to maintain blinding.
ABCWY_Pooled	MenABCWY-2	Participants received 2 doses of either MenABCWY Lot 1, Lot 2, or Lot 3 vaccine on Day 1 and Day 181 and 1 dose of placebo on Day 61. Participants received 1 dose of placebo on Day 211 to maintain blinding. To evaluate the effectiveness of 2 doses of the MenABCWY vaccines against rMenB+OMV and MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
MenB_0_6 Group	Placebo	Participants received 2 doses of rMenB+OMV NZ vaccine on Day 1, and Day 181, 1 dose of MenACWY vaccine on Day 61. Participants received 1 dose of Placebo on Day 211 to maintain blinding.
ABCWY_Pooled	MenABCWY-3	Participants received 2 doses of either MenABCWY Lot 1, Lot 2, or Lot 3 vaccine on Day 1 and Day 181 and 1 dose of placebo on Day 61. Participants received 1 dose of placebo on Day 211 to maintain blinding. To evaluate the effectiveness of 2 doses of the MenABCWY vaccines against rMenB+OMV and MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
ACWY Group	rMenB+OMV NZ vaccine	Participants received 1 dose of MenACWY vaccine at Day 1,1 dose of placebo at Day 61 and 1 dose of rMenB+OMV NZ vaccine on Day 181. Participants received 1 dose of rMenB+OMV NZ vaccine on Day 211 as standard of care.
ACWY Group	Placebo	Participants received 1 dose of MenACWY vaccine at Day 1,1 dose of placebo at Day 61 and 1 dose of rMenB+OMV NZ vaccine on Day 181. Participants received 1 dose of rMenB+OMV NZ vaccine on Day 211 as standard of care.
ABCWY_Pooled	MenABCWY-1	Participants received 2 doses of either MenABCWY Lot 1, Lot 2, or Lot 3 vaccine on Day 1 and Day 181 and 1 dose of placebo on Day 61. Participants received 1 dose of placebo on Day 211 to maintain blinding. To evaluate the effectiveness of 2 doses of the MenABCWY vaccines against rMenB+OMV and MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
MenB_0_2_6 Group	rMenB+OMV NZ vaccine	Participants received 3 doses of rMenB+OMV NZ vaccine on Day 1, Day 61 and Day 181. Participants received 1 dose of MenACWY vaccine at Day 211 as a standard of care.
ABCWY-1 Group	Placebo	Participants received 2 doses of MenABCWY lot 1 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211.
ABCWY-2 Group	Placebo	Participants received 2 doses of MenABCWY lot 2 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211.
ABCWY-3 Group	Placebo	Participants received 2 doses of MenABCWY lot 3 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211.
MenB_0_6 Group	Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY)	Participants received 2 doses of rMenB+OMV NZ vaccine on Day 1, and Day 181, 1 dose of MenACWY vaccine on Day 61. Participants received 1 dose of Placebo on Day 211 to maintain blinding.
ABCWY-1 Group	MenABCWY-1	Participants received 2 doses of MenABCWY lot 1 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211.
ABCWY-2 Group	MenABCWY-2	Participants received 2 doses of MenABCWY lot 2 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211.
ACWY Group	Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY)	Participants received 1 dose of MenACWY vaccine at Day 1,1 dose of placebo at Day 61 and 1 dose of rMenB+OMV NZ vaccine on Day 181. Participants received 1 dose of rMenB+OMV NZ vaccine on Day 211 as standard of care.

Primary Outcome Measures

Name	Time	Method
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)	At 1 month after the last vaccination of MenABCWY (Day 211)	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. Effectiveness is demonstrated Lower Limit (LL) of the two-sided 97.5% CI for the percentages of participants whose sera kill ≥70% of strains tested for MenABCWY is above 65%.
Number of Participants With Any Solicited Local Adverse Events (AEs) After the Second Study Intervention Administration	During 7 days after the second study intervention administration occurring at Day 61	Assessed solicited local adverse events were injection or administration site pain, erythema, swelling, induration. Any = occurrence of the adverse event regardless of intensity grade. Any erythema and swelling = adverse event reported with a surface diameter greater than 0 millimeters. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.
Percentage of Participants Whose Sera Kill Greater Than or Equal to (>=) 70% of the Strains Tested Using Enc-hSBA at 1 Month After the 3-dose (0,2,6-M) Schedule of rMenB+OMV and 2-dose(0,6-M) Schedule of rMenB+OMV	At 1 month after vaccination schedule (i.e., Day 211 for MenB_0_2_6 group [3-dose schedule] and MenB_0_6 group)	The effectiveness (responder-based) of the rMenB+OMV NZ vaccine was measured in terms of percentage of participants whose sera kill \>=70% of the strains tested using enc-hSBA, calculated based on Clopper Pearson method. Effectiveness is demonstrated if Lower Limit (LL) of the two-sided 97.5% CI for the percentages of participants whose sera kill ≥70% of strains is above 65%.
Percentage of Blood 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 2-dose(0,2-M) Schedule of rMenB+OMV	At 1 month after the vaccination schedule (i.e., Day 211 for the ABCWY_Pooled group and Day 91 for the MenB_0_2_6 Group [2-dose schedule])	The effectiveness was 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. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 Group and ABCWY pooled group to evaluate the effectiveness of 2 doses of the MenABCWY vaccines against MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
Number of Participants With Any Solicited Local Adverse Events (AEs) After the First Study Intervention Administration	During 7 days after the first study intervention administration occurring at Day 1	Assessed solicited local adverse events were injection or administration site = pain, erythema, swelling, induration. Any = occurrence of the adverse event regardless of intensity grade. Any erythema and swelling = adverse event reported with a surface diameter greater than 0 millimeters. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.
Number of Participants With Any Solicited Systemic AEs After the Second Study Intervention Administration	During 7 days after the second study intervention administration occurring at Day 61	Assessed solicited systemic AEs were fatigue, nausea, myalgia, arthralgia, headache and fever \[temperature \>= 38.0°C\]. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.
Percentage of Blood 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), 2-dose(0,6-M) Vaccination Schedule of rMenB+OMV and 1 Dose of MenACWY	At 1 month after vaccination schedule (i.e., Day 211 for MenB_0_2_6 group [3-dose schedule] and MenB_0_6 group, and Day 31 for ACWY group)	The effectiveness (test-based) of rMenB+OMV vaccine at 1 month after the 3 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 was 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.; Participants were randomly selected for testing against each strain therefore only a subset of participants were tested for each of the strains.
Number of Participants With Any Solicited Systemic AEs After the First Study Intervention Administration	During 7 days after the first study intervention administration occurring at Day 1	Assessed solicited systemic AEs were fatigue, nausea, myalgia, arthralgia, headache and fever \[temperature \>= 38.0°C\]. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.
Number of Participants With Any Solicited Systemic AEs After the Third Study Intervention Administration	During 7 days after the third study intervention administration occurring at Day 181	Assessed solicited systemic AEs were fatigue, nausea, myalgia, arthralgia, headache and fever \[temperature \>= 38.0°C\]. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.
Number of Participants With Any Unsolicited AEs After the Second Study Intervention Administration	During the 30 days after the second study intervention administration occurring at Day 61	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 were reported as an unsolicited AE. Any Unsolicited AEs (including Serious adverse events (SAEs), AEs leading to withdrawal, Adverse event of special interest (AESIs) and medically attended AEs were collected during 30 days after vaccination 1-3. For vaccination on Day 211 (Vaccination 4), conducted as part of standard of care and to maintain blinding, no eDiary data or all unsolicited AEs were collected for the 30 days following vaccination. However, SAEs, AEs leading to withdrawal, AESIs and medically attended AEs were collected throughout study duration. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.
Percentage of Participants Whose Sera Kill >=70% of the Strains Tested Using Enc-hSBA at 1 Month After the 2-dose (0,2-M) Schedule of rMenB+OMV	At 1 month after vaccination schedule (i.e., Day 91 for the MenB_0_2_6 group [2-dose schedule])	The effectiveness (responder-based) of the rMenB+OMV NZ vaccine was measured in terms of percentage of participants whose sera kill \>=70% of the strains tested using enc-hSBA, calculated based on Clopper Pearson method. Effectiveness is demonstrated if Lower Limit (LL) of the two-sided 97.5% CI for the percentages of participants whose sera kill ≥70% of strains is above 65%.
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	At 1 month after the last vaccination of MenABCWY (Day 211)	Immune response was measured in terms of hSBA GMTs directed against serogroups A, C, W and Y. As pre-specified in the protocol, the data reported in this outcome measures data were presented for individual lots to demonstrate the consistency of the immune response of 3 lots (ABCWY- 1 Group, ABCWY-2 Group, and ABCWY-3 Group) of the ACWY component of the MenABCWY vaccine.
Percentage of Blood Samples Without Bactericidal Serum Activity Against Each of the Endemic U.S N. Meningitidis Serogroup B Strains at 1 Month After Last MenABCWY Vaccination (Pooled Lots) and MenACWY Vaccination (for the ACWY Group)	At 1 month after the vaccination schedule (i.e., Day 211 for the ABCWY_Pooled group and Day 31 for the 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 was 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.; As pre-specified in the protocol, data reported in this outcome measure were presented for ACWY group and ABCWY pooled group to evaluate the effectiveness of 2 doses of the MenABCWY vaccines against MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
Percentage of Blood Samples Without Bactericidal Serum Activity Against Each of the Endemic US N. Meningitidis Serogroup B Strains at 1 Month After the 2-dose (0,2-M) Vaccination Schedule of rMenB+OMV and 1 Dose of MenACWY	At 1 month after vaccination schedule (i.e., Day 91 for the MenB_0_2_6 group [2-dose schedule] and Day 31 for ACWY group)	The effectiveness (test-based) of rMenB+OMV vaccine at 1 month after the 2 doses in MenB_0_2_6 group when compared to one dose of MenACWY vaccination in ACWY group, against a panel of N. meningitidis serogroup B strains was 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.; Participants were randomly selected for testing against each strain therefore only a subset of participants were tested for each of the strains.
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	At 1 month after vaccination schedule (i.e., Day 211 for the ABCWY_Pooled group and Day 31 for the ACWY Group) compared to Day 1 (baseline)	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.; As pre-specified in the protocol, data reported in this outcome measure were presented for ACWY group, ABCWY pooled group to evaluate the immunological non-inferiority of 2 doses of the MenABCWY vaccines against MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
Number of Participants With Any Solicited Local Adverse Events (AEs) After the Third Study Intervention Administration	During 7 days after the third study intervention administration occurring at Day 181	Assessed solicited local adverse events were injection or administration site pain, erythema, swelling, induration. Any = occurrence of the adverse event regardless of intensity grade. Any erythema and swelling = adverse event reported with a surface diameter greater than 0 millimeters. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.
Number of Participants With Any Unsolicited AEs After the Third Study Intervention Administration	During the 30 days after the third study intervention administration occurring at Day 181	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 were reported as an unsolicited AE. Any Unsolicited AEs (including Serious adverse events (SAEs), AEs leading to withdrawal, Adverse event of special interest (AESIs) and medically attended AEs were collected during 30 days after vaccination 1-3. For vaccination on Day 211 (Vaccination 4), conducted as part of standard of care and to maintain blinding, no eDiary data or all unsolicited AEs were collected for the 30 days following vaccination. However, SAEs, AEs leading to withdrawal, AESIs and medically attended AEs were collected throughout study duration. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.
Number of Participants With SAEs, AEs Leading to Withdrawal, AESIs and Medically Attended AEs	Throughout the study period (Day 1 to Day 361)	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. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.
Number of Participants With Any Unsolicited AEs After the First Study Intervention Administration	During the 30 days after the first study intervention administration occurring at Day 1	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 were reported as an unsolicited AE. Any Unsolicited AEs (including Serious adverse events (SAEs), AEs leading to withdrawal, Adverse event of special interest (AESIs) and medically attended AEs were collected during 30 days after vaccination 1-3. For vaccination on Day 211 (Vaccination 4), conducted as part of standard of care and to maintain blinding, no eDiary data or all unsolicited AEs were collected for the 30 days following vaccination. However, SAEs, AEs leading to withdrawal, AESIs and medically attended AEs were collected throughout study duration. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group.

Secondary Outcome Measures

Name	Time	Method
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 2-dose(0,2-M) Schedule of rMenB+OMV NZ Relative to Baseline	At 1 month after the vaccination schedule (i.e., Day 211 for the ABCWY_Pooled group and Day 91 for the MenB_0_2_6 Group [2-dose schedule]) compared to Day 1 (Baseline)	The immunogenicity is measured as 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). 4-fold rise per each indicator strain was 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 and \<LLOQ; a post-vaccination hSBA titre ≥4 times the pre-vaccination hSBA titre for participants with a pre-vaccination hSBA titre ≥ LLOQ. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 Group and ABCWY pooled group to evaluate the effectiveness of 2 doses of the MenABCWY vaccines against MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
Percentage of Participants Classified by Percentage of Serogroup B Invasive Disease Strains Killed Using Enc-hSBA in Each Subject at 1 Month After Vaccination Schedule for the MenB_0_2_6 Group [3 Dose], MenB_0_6 Group and Last MenABCWY Dose (Pooled Lots)	At 1 month after the vaccination schedule (Day 211 for MenB_0_2_6 group (3 dose schedule), MenB_0_6 group and ABCWY_Pooled group)	The percentage of participants 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. As pre-specified in the protocol, data reported in this outcome measure were presented for the MenB_0_2_6 group, MenB_0_6 group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
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-months)	At Day 1 (pre-vaccination) and1 month after the vaccination schedule (i.e., Day 91 for MenB_0_2_6 group [2 dose schedule])	The immune response to rMenB+OMV NZ is evaluated by measuring bactericidal activity against each (individual response) and all (composite response) N. meningitidis serogroup B indicator strains (M14459, 96217, M13520 and NZ98/254 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively).
hSBA GMTs Against Each of the N. Meningitidis Serogroup B Strains at Day 1 and at 1 Month After Vaccination With rMenB+OMV NZ (0,2-months)	At Day 1 (pre-vaccination) and at 1 month after the vaccination schedule (i.e., Day 91 for MenB_0_2_6 group[2-dose schedule])	The immune response to rMenB+OMV NZ and MenABCWY vaccine was 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 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively), The GMTs (After vaccination/baseline) were calculated, with their associated 2-sided 95% CIs.
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 and 0,6-months) and Last Dose of MenABCWY (ABCWY Group-pooled Lots)	At Day 1 (pre-vaccination) and1 month after the vaccination schedule (i.e., Day 211 for MenB_0_2_6 group [3 dose schedule], MenB_0_6 group and ABCWY_Pooled group)	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, M13520 and NZ98/254 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively). As pre-specified in the protocol, data reported in this outcome measure were presented for the MenB_0_2_6 group, MenB_0_6 group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
hSBA Geometric Mean Titres (GMTs) Against Each of the N. Meningitidis Serogroup B Strains at Day 1 and at 1 Month After Vaccination With rMenB+OMV NZ (0,2,6-months, 0,6-months) and Last Dose of MenABCWY (ABCWY Group-pooled Lots)	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 and ABCWY_Pooled group)	The immune response to rMenB+OMV NZ and MenABCWY vaccine was 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 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively), The GMTs (After vaccination/baseline) are calculated, with their associated 2-sided 95% CIs. As pre-specified in the protocol, data reported in this outcome measure were presented for the MenB_0_2_6 group, MenB_0_6 group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
hSBA GMRs for Each of the N. Meningitidis Serogroup B Strains at 1 Month After Vaccination With rMenB+OMV NZ (0,2-months)	At 1 month after the vaccination schedule (i.e., Day 91 for MenB_0_2_6 group [2-dose schedule]) compared to Day 1 (baseline)	The immune response to rMenB+OMV NZ vaccine was 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 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively), the GMRs (after vaccination/baseline) are calculated, with their associated 2-sided 95% CIs.
Percentage of Blood 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 and 3-dose (0,2,6-M), 2-dose(0,6-M) Schedule of rMenB+OMV and 1 Dose of MenACWY	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_Pooled group and Day 31 for the MenACWY group)	The effectiveness of the 3 dose (0,2,6-M) and 2 dose (0,6-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. As pre-specified in the protocol, data reported in this outcome measure were presented for the MenB_0_2_6 group, MenB_0_6 group,ACWY group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
Percentage of Blood Samples Without Bactericidal Serum Activity Using Enc-hSBA Against Each of the Endemic U.S N. Meningitidis Serogroup B Strains at 1 Month After the 2-dose(0,6-M) Schedule of rMenB+OMV and 1 Dose of MenACWY	At 1 month after the vaccination schedule (i.e., Day 91 for the MenB_0_2_6 group [2 dose schedule] and Day 31 for the MenACWY group)	The effectiveness of the 2 dose (0,2-M) schedule of rMenB+OMV NZ 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.
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 and 0,6-months) and Last Dose of MenABCWY (ABCWY Group-pooled Lots)	At 1 month after the vaccination schedule (i.e., Day 211 for MenB_0_2_6 group [3 dose schedule], MenB_0_6 group and ABCWY_Pooled group) compared to Day 1 (baseline)	The immune response to 3 dose (0,2,6-M), 2 dose (0,6-M) schedule of rMenB+OMV NZ and 2 doses of MenABCWY vaccine was evaluated by measuring bactericidal activity against each of the N. meningitidis serogroup B test strains- M14459, 96217, NZ98/254 and M13520 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively compared to baseline. Four-fold rise per each indicator strain was defined as a post-vaccination hSBA titre ≥16 for subjects with a pre-vaccination hSBA titre \<4 a post-vaccination hSBA titer ≥4 times the LLOQ for subjects with a pre-vaccination hSBA titre ≥LOD and \<LLOQ a post-vaccination hSBA titre ≥4 times the pre-vaccination hSBA titre for participants with a pre-vaccination hSBA titre ≥ LLOQ. As pre-specified in the protocol, data reported in this outcome measure were presented for the MenB_0_2_6 group, MenB_0_6 group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
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 Months)	At 1 month after the vaccination schedule (i.e., Day 91 for MenB_0_2_6 [2-dose schedule]) compared to Day 1 (baseline)	The immune response to 2 dose (0,2-M) is evaluated by measuring bactericidal activity against each of the N. meningitidis serogroup B test strains- M14459, 96217, NZ98/254 and M13520 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively compared to baseline. Four-fold rise per each indicator strain was 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 subjects with a pre-vaccination hSBA titre ≥LOD and \<LLOQ a post-vaccination hSBA titre ≥4 times the pre-vaccination hSBA titre for subjects with a pre-vaccination hSBA titre ≥ LLOQ.
hSBA GMTs Against Each of the N. Meningitidis Serogroups A, C, W and Y at Day 1 and 1 Month After the First and the Last MenABCWY Vaccination for the ABCWY_Pooled Group and at 1 Month After the MenACWY Vaccination for ACWY 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])	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. As pre-specified in the protocol, data reported in this outcome measure were presented for the ACWY group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
Total Immunoglobulin G (IgG) Antibodies Concentrations Against N. Meningitidis Serogroups A, C, W and Y at Day 1 and 1 Month After the First and the Last MenABCWY Vaccination for ABCWY _Pooled Group and 1 Month After the MenACWY Vaccination for ACWY 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])	The immune responses to MenABCWY and MenACWY vaccines were evaluated by measuring the total IgG in terms of electrochemiluminescence-based multiplex (ECL) geometric mean concentrations (GMCs) which was an alternative assay to Enzyme-Linked Immunosorbent Assay (ELISA). ECL (validated assay) was used because ELISA is not validated. As pre- specified in the protocol, data reported in this outcome measure were presented for the ACWY group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
Percentage of Participants Classified by Percentage of Serogroup B Invasive Disease Strains Killed Using Enc-hSBA in Each Subject at 1 Month After Vaccination With rMenB+OMV NZ (0,2-months)	At 1 month after the vaccination schedule (Day 91 for MenB_0_2_6 group [2 dose schedule])	The percentage of participants 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.
hSBA 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 Last Dose of MenABCWY (ABCWY Group-pooled Lots)	At 1 month after the vaccination schedule (i.e., Day 211 for MenB_0_2_6 group (3 dose schedule), MenB_0_6 group and ABCWY_Pooled group) compared to Day 1 (baseline)	The immune response to rMenB+OMV NZ vaccine was 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 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively), the GMRs (after vaccination/baseline) are calculated, with their associated 2-sided 95% CIs. As pre-specified in the protocol, data reported in this outcome measure were presented for the MenB_0_2_6 group, MenB_0_6 group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
Percentage of Participants With hSBA Titers >= LLOQ for Each of the N. Meningitidis Serogroups A,C,W,Y at Day 1 and at 1 Month After the First and the Last MenABCWY Vaccination for ABCWY_Pooled Group and 1 Month After the MenACWY Vaccine for ACWY 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])	The immune responses to MenABCWY and MenACWY vaccines were 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. As pre-specified in the protocol, data reported in this outcome measure were presented for the ACWY group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
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 ABCWY_Pooled Group Compared to the MenACWY Vaccine for ACWY Group Relative to Baseline (Day 1)	At 1 month after vaccination schedule (i.e, at Day 31 for ABCWY group [pooled group] and for ACWY Group) relative to baseline (Day 1)	The immune response to MenABCWY vaccine compared to MenACWY vaccine was 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. As pre-specified in the protocol, data reported in this outcome measure were presented for the ACWY group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.
GMRs for Each of the N. Meningitidis Serogroups A, C, W and Y at 1 Month After the First and the Last MenABCWY Vaccination for the ABCWY _Pooled Group and at 1 Month After the MenACWY Vaccination for ACWY Group	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]) compared to baseline (Day 1)	The immune responses to MenABCWY and MenACWY vaccines are evaluated by measuring bactericidal activity against N. meningitidis serogroups A, C, W and Y. For each N. meningitidis serogroups A, C, W and Y, the GMRs (after vaccination/baseline) are calculated, with their associated 2-sided 95% CIs. As pre-specified in the protocol, data reported in this outcome measure were presented for the ACWY group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.

Trial Locations

Locations (1)

GSK Investigational Site; 🇹🇷 Kayseri, Turkey