Combined Study - Phase 3b MenB Long Term Persistence in Adolescents

Study Overview
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Brief Summary
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The purpose/aim of this study is to assess 1) the long-term persistence (4 to 7.5 years after the last dose) of bactericidal activity following primary vaccination with rMenB+OMV NZ in adolescents [who previously participated in parent studies V72_41 (NCT0142384) and V72P10 (NCT00661713)] and 2) the kinetics of immune response following booster vaccination with rMenB+OMV NZ

Detailed Description
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After all subjects (Groups A and B) from Canada and Australia have completed the study, an interim analysis for the primary and secondary immunogenicity objectives will be performed. Follow on subjects (Group A) from parent study V72_41 (NCT0142384) will be analyzed for i) antibody persistence at approximately 4 years following a 2 dose primary series and ii) the immune response at 3, 7 and 30 days after a third dose (booster) of rMenB+OMV NZ. Canadian and Australian vaccine naïve subjects (Group B) will be analyzed for the immune response at 30 days after the first dose, and 3, 7 and 30 days after the second dose of rMenB+OMV NZ. Subjects in Group B (naïve subjects) will be randomized into two different blood draw schedules according to a 1:1 ratio.

Official Title
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A Phase 3b, Open Label, Controlled, Multi-Center, Extension Study to Assess the Persistence of Bactericidal Activity at 4 to 7.5 Years After Two Dose Primary Series of GlaxoSmithKline Biologicals Meningococcal B Recombinant Vaccine and the Response to a Third Dose in Adolescents and Young Adult Subjects Who Previously Participated in Parent Studies V72_41 (NCT01423084) and V72P10 (NCT00661713), Compared to Naïve Healthy Controls

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Biological: rMenB+OMV NZ (Meningococcal (Group B) multi component recombinant adsorbed vaccine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criterion for follow-on subjects: Individuals who participated to Study V72_41 or V72P10 and have completed vaccination with rMenB+OMV NZ according to a 2-dose schedule Inclusion Criterion for naïve subjects: Individuals of 15 through 21 years of age on the day of informed consent and assent as applicable (according to the subject's age) for subjects enrolled at sites that participated to Study V72_41. 17 through 24 years of age on the day of informed consent and assent as applicable (according to the subject's age) for subjects enrolled at sites that participated to Study V72P10. Inclusion Criteria for all subjects: Individuals who have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. Individuals who can comply with study procedures including follow-up. Males Or Females of non-childbearing potential Or Females of childbearing potential who are using an effective birth control method . Exclusion Criteria for all subjects Exclusion Criterion for follow-on subjects: • Received a third dose of a Meningococcal group B vaccine prior to enrolment in this study. Exclusion Criterion for naïve subjects: • Received any other Meningococcal group B vaccines prior to enrolment in this study. Exclusion Criteria for all subjects: Progressive, unstable or uncontrolled clinical conditions. Hypersensitivity, including allergy, to any component of vaccines or medical equipment whose use is foreseen in this study. Abnormal function of the immune system. Received immunoglobulins or any blood products within 180 days prior to informed consent and assent as applicable (according to the subject's age). Received an investigational or non-registered medicinal product within 30 days prior to informed consent and assent as applicable (according to the subject's age). Study personnel as an immediate family or household member. Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study. Positive results at the urine pregnancy test performed before study vaccination.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 24 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 3B<br>Subjects who received a third dose booster of rMenB+OMV NZ at 4 to 7.5 years after the last dose received during studies V72P10 (NCT00661713) or V72_41(NCT0142384), and had blood collected at baseline and at 3, 7 and 30 days after the third dose booster. | Biological: rMenB+OMV NZ (Meningococcal (Group B) multi component recombinant adsorbed vaccine)<br>* One dose of the vaccine administered intramuscularly in the deltoid area of the non-dominant arm.<br>|
| Active Comparator: Group B_0_1<br>Subjects who received two doses of rMenB+OMV NZ at a 0 and 1 month schedule and had blood collected at baseline, 30 days after the first dose and 3 or 7, and 30 days after the second dose. | Biological: rMenB+OMV NZ (Meningococcal (Group B) multi component recombinant adsorbed vaccine)<br>* One dose of the vaccine administered intramuscularly in the deltoid area of the non-dominant arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Human Serum Bactericidal Activity (hSBA)≥1:4 | Bactericidal activity was measured against the N. meningitidis group B indicator strains 5/99 and NZ98/254. This outcome measure was assessed only for strains 5/99 and NZ98/254. | Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose). | 
| Percentage of Subjects With hSBA≥1:5 | Bactericidal activity was measured against the N. meningitidis group B indicator strains H44/76 and M10713. This outcome measure was assessed only for strains H44/76 and M10713. | Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose). | 
| Percentage of Subjects With hSBA Titers≥1:5 in Parent Studies-V72P10 and V72_41 | Bactericidal activity was measured against the N. meningitidis group B indicator strains H44/76 and M10713 | At one month after last vaccination in parent studies- V72P10 (Month 7) and V72_41 (Month 2) | 
| Percentage of Subjects With hSBA≥1:8 | Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713 | Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose). | 
| Percentage of Subjects With hSBA≥1:16 | Bactericidal activity was measured against each of the N. meningitidis group B Indicator strains H44/76,5/99,NZ98/254 and M10713 | Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose). | 
| hSBA Geometric Mean Titers (GMTs) After the Last Dose of rMenB+OMV NZ Vaccination in the Parent Study. | Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76,5/99, NZ98/254 a nd M10713. | Group 3B: 1 month after the last rMenB+OMV NZ vaccination in parent study and Day 1(prior to booster dose); Group B_0_1: Day 1(prior to first dose) | 
| Geometric Mean Ratios (GMRs) of GMTs After the Last Dose of rMenB+OMV NZ Vaccination in the Parent Study Versus Day 1. | The GMRs of GMTs at Day 1 versus one month after the last dose of rMenB+OMV NZ vaccination in the parent study were calculated. Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76, 5/99,NZ98/254 and M10713. | Group 3B: 1 month after the last vaccination in parent study and Day 1 (prior to booster dose) | 
| Number of Subjects With Solicited Local and Systemic AEs. | Solicited adverse events are signs and symptoms derived from organized data collection systems, such as Subject Diaries or interview. The percentage and frequencies of subjects reporting solicited local and systemic AEs were tabulated. Threshold for any Erythema, Swelling and Induration: >= 25 mm Note:Vaccination 2 was performed only on group B_0_1 subjects. Threshold for any Erythema, Swelling and Induration: >= 25 mm | 7 days (including the day of vaccination) after each vaccination | 
| Number of Subjects With Any Unsolicited Adverse Events (AEs). | An unsolicited adverse event is an adverse event that was not solicited using a subject Diary and that was spontaneously communicated by a subject and/or parent(s)/legal guardian(s) who has signed the informed consent. Note : Vaccination 2 was performed only on group B_0_1 subjects. | 30 days (including the day of vaccination) after each vaccination. | 
| Number of Subjects With Any SAEs, AEs Leading to Withdrawal and Medically Attended AEs. | A serious adverse event is any untoward medical occurrence that at any dose results in death or is life threatening or requires prolonged hospitalization, leads to Persistent or significant disability/incapacity. | Group 3B: from Day 1 to Day 31 (study termination visit) and Group B_0_1: from Day 1 to Day 61 (study termination visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With hSBA ≥1:4 After Booster Dose/First Vaccination of rMenB+OMV NZ. | Bactericidal activity was measured against the N. meningitidis group B indicator strains 5/99 and NZ98/254. This outcome measure was assessed only for strains 5/99 and NZ98/254. | Group 3B: 30 days after booster dose, Group B_0_1 : 30 days after first vaccination. | 
| Percentage of Subjects With hSBA ≥1:5 After Booster Dose/First Vaccination of rMenB+OMV NZ. | Bactericidal activity was measured against the N. meningitidis group B indicator strains H44/76 and M10713. This outcome measure was assessed only for strains H44/76 and M10713. | Group 3B: 30 days after booster dose, Group B_0_1 : 30 days after first vaccination. | 
| Percentage of Subjects With hSBA ≥1:8 After Booster Dose/First Vaccination of rMenB+OMV NZ | Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. | Group 3B : 30 days after booster dose, Group B_0_1 : 30 days after first vaccination. | 
| Percentage of Subjects With hSBA ≥1:16 After Booster Dose/First Vaccination of rMenB+OMV NZ | Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 & M10713. | Group 3B: 30 days after booster dose, Group B_0_1 : 30 days after first vaccination. | 
| hSBA Geometric Mean Titers Prior to Booster/First Dose of Vaccination & Post Booster/First Dose of Vaccination. | Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99,NZ98/254 and M10713. | Group 3B subjects: Day 1(pre-booster dose) and 30 days post-booster dose. Group B_0_1: Day 1 (pre-first dose) and 30 days post-first dose. | 
| Geometric Mean Ratio (GMRs) of GMTs After Booster Dose/First rMenB+OMV NZ Vaccination Versus Day 1. | Bactericidal activity was measured against each of the fout N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713 by calculating the GMRs of GMTs one month post-vaccination of a booster dose versus pre-booster dose (follow-on subjects) or first dose of rMenB+OMV NZ versus prefirst dose (naïve subjects) to each N. meningitidis group B indicator strain. | At Day 31 (30 days post booster dose/first dose of vaccination) versus Day 1 (prior to booster dose/first dose of vaccination). | 
| Percentages of Subjects With at Least 4-fold Increase in hSBA Titers Pre Vaccination Compared to One Month Post-booster/First rMenB+OMV NZ Vaccination | The percentage of subjects with 4-fold rise at one month post-vaccination with a booster dose (follow-on subjects) /first dose (naive subjects) of rMenB+OMV NZ with respect to day 1 (follow-on subjects) / pre-first dose of rMenB+OMV NZ (naïve subjects). Percentage of subjects with four-fold rise in hSBA titers relative to baseline were defined as: • for a pre-vaccination titer < 4, a post-vaccination titer of at least 16; • for a pre-vaccination titer ≥ 4 but <LLOQ, a post vaccination titer of at least fourfold the LLOQ; • for a pre-vaccination titer ≥LLOQ, a post vaccination titer of at least fourfold the pre-vaccination titer | Group 3B: 1 month after booster dose; Group B_0_1: 1 month after first vaccination | 
| Percentage of Subjects With hSBA ≥1:4 After Booster Dose/Second Vaccination of rMenB+OMV NZ | Bactericidal activity was measured against the N. meningitidis group B indicator strains 5/99 and NZ98/254. On day 1, subjects in the Group B_0_1 were to be randomized into 2 different blood draw schedules according to a 1:1 ratio : 2 blood samples at different time points: Group B_0_1_1: blood draws at 3 and 30 days after the second dose. Group B_0_1_2: blood draws at 7 and 30 days after the second dose. This outcome measure was assessed only for strains 5/99 and NZ98/254. | Group 3B: 3, 7 and 30 days after third dose booster; Group B_0_1: At 3 (group B_0_1_1 only), 7 (sub-group B_0_1_2 only) and 30 days post-second dose. | 
| Percentage of Subjects With hSBA ≥1:5 After Booster Dose/Second Vaccination of rMenB+OMV NZ | Bactericidal activity was measured against the N. meningitidis group B indicator strains H44/76 and M10713. On day 1, subjects in the Group B_0_1 were to be randomized into 2 different blood draw schedules according to a 1:1 ratio : 2 blood samples at different time points: Group B_0_1_1: blood draws at 3 and 30 days after the second dose. Group B_0_1_2: blood draws at 7 and 30 days after the second dose. This outcome measure was assessed only for strains H44/76 and M10713. | Group 3B: 3, 7 and 30 days after third dose booster; Group B_0_1: At 3 (group B_0_1_1 only), 7 (sub-group B_0_1_2 only) and 30 days post-second dose. | 
| Percentage of Subjects With hSBA ≥1:8 After Booster Dose/Second Vaccination of rMenB+OMV NZ | Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. On day 1, subjects in the Group B_0_1 were to be randomized into 2 different blood draw schedules according to a 1:1 ratio : 2 blood samples at different time points: Group B_0_1_1: blood draws at 3 and 30 days after the second dose. Group B_0_1_2: blood draws at 7 and 30 days after the second dose. | Group 3B: 3, 7 and 30 days after third dose booster; Group B_0_1: At 3 (group B_0_1_1 only), 7 (sub-group B_0_1_2 only) and 30 days post-second dose. | 
| Percentage of Subjects With hSBA ≥1:16 After Booster Dose/Second Vaccination of rMenB+OMV NZ | Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. On day 1, subjects in the Group B_0_1 were to be randomized into 2 different blood draw schedules according to a 1:1 ratio : 2 blood samples at different time points: Group B_0_1_1: blood draws at 3 and 30 days after the second dose. Group B_0_1_2: blood draws at 7 and 30 days after the second dose | Group 3B: 3, 7 and 30 days after third dose booster; Group B_0_1: At 3 (group B_0_1_1 only), 7 (sub-group B_0_1_2 only) and 30 days post-second dose | 
| hSBA Geometric Mean Titers Prior to Booster/Second Dose of Vaccination & Post Booster/Second Dose of Vaccination. | Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. On day 1, subjects in the Group B_0_1 were to be randomized into 2 different blood draw schedules according to a 1:1 ratio : 2 blood samples at different time points: Group B_0_1_1: blood draws at 3 and 30 days after the second dose. Group B_0_1_2: blood draws at 7 and 30 days after the second dose. | Group 3B: Day 1 (pre-booster dose) and 3, 7 and 30 days after third dose booster; Group B_0_1: Pre 2nd dose and at 3 (group B_0_1_1 only), 7 (group B_0_1_2 only) and 30 days post second dose. | 
| Geometric Mean Ratios (GMRs) of GMTs After Booster/Second Vaccination Versus Before Booster/Second Vaccination. | Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713 by calculating the GMRs of GMTs post-vaccination with a booster dose (Group 3B) versus pre-booster dose or second dose (Group B_0_1) of vaccination versus pre second dose. | Group 3B: Day 1 and 30 days after third dose booster; Group B_0_1: 30 days post-first dose and at 30 days post-second dose | 
| Percentages of Subjects With at Least Four-fold Increase in hSBA Titers Pre-booster/Second Dose Vaccination- Compared to 3, 7 and 30 Days Post- Booster/Second Vaccination | The percentage of subjects with 4-fold rise at 3, 7, 30 days post-vaccination with a booster dose (follow-on subjects) /second dose (naive subjects) of rMenB+OMV NZ with respect to day 1 (follow-on subjects) / pre-second dose of rMenB+OMV NZ (naïve subjects). Percentage of subjects with four-fold rise in hSBA titers relative to baseline were defined as: • for a pre-vaccination titer < 4, a post-vaccination titer of at least 16; • for a pre-vaccination titer ≥ 4 but <LLOQ, a post vaccination titer of at least fourfold the LLOQ; • for a pre-vaccination titer ≥LLOQ, a post vaccination titer of at least fourfold the pre-vaccination titer. | Group 3B: at 3, 7 and 30 days after third dose booster; Group B_0_1: at 3 (group B_0_1_1 only), 7 (group B_0_1_2 only) and 30 days post second dose | 
| Percentage of Subjects With hSBA ≥1:4 After Second Vaccination of rMenB+OMV NZ | Bactericidal activity was measured against the N. meningitidis group B indicator strains 5/99 and NZ98/254. Only subjects receiving a second vaccination (group B_0_1) were assessed for this outcome measure. | At Day 61 (30 days post second dose of vaccination.) | 
| Percentage of Subjects With hSBA ≥1:5 After Second Vaccination of rMenB+OMV NZ | Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76 and M10713. Only subjects receiving a second vaccination (group B_0_1) were assessed for this outcome measure. | At Day 61 (30 days post second dose of vaccination.) | 
| Percentage of Subjects With hSBA ≥1:8 After Second Vaccination of rMenB+OMV NZ. | Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. Only subjects receiving a second vaccination (group B_0_1) were assessed for this outcome measure. | At Day 61 (30 days post second vaccination) | 
| Percentage of Subjects With hSBA ≥1:16 After Second Vaccination of rMenB+OMV NZ. | Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. Only subjects receiving a second vaccination (group B_0_1) were assessed for this outcome measure. | At Day 61 (30 days post second vaccination) | 
| hSBA Geometric Mean Titers (GMTs) After Second Vaccination of rMenB+OMV NZ. | Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. Only subjects receiving a second vaccination (group B_0_1) were assessed for this outcome measure. | At Day 1 & Day 61 (30 days post second dose of vaccination) | 
| Geometric Mean Ratio (GMRs) of GMTs One Month Post Second Vaccination Versus Pre Vaccination at Day 1 | Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. Only subjects receiving a second vaccination (group B_0_1) were assessed for this outcome measure. | At Day 1 & Day 61 (30 days post 2nd vaccination) | 
| Percentages of Subjects With at Least Four-fold Increase in hSBA Titers at Pre-First Vaccination Compared to One Month Post-Second Vaccination | The percentage of subjects with 4-fold rise at one month post-vaccination with a second dose (naïve subjects) of rMenB+OMV NZ with respect to day 1, to each and any one, two, three or all 4 indicator strains. Percentage of subjects with four-fold rise in hSBA titers relative to baseline were defined as: for a pre-vaccination titer < 4, a post-vaccination titer of at least 16; for a pre-vaccination titer ≥ 4 but <LLOQ, a post vaccination titer of at least fourfold the LLOQ; for a pre-vaccination titer ≥LLOQ, a post vaccination titer of at least fourfold the pre-vaccination titer. Only subjects receiving the second dose of vaccination(group B_0_1) were considered for this outcome measure. | At Day 61 (30 days post second dose of vaccination) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Central Nervous System Diseases, Nervous System Diseases, Meningitis