Clinical trial NCT02446743: Combined Study - Phase 3b MenB Long Term Persistence in Adolescents
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Meningococcal
Keywords: Nervous System Diseases
Meningitis
Central Nervous System Diseases
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2015-05-18
Enrollment: 531
Sex: ALL
Minimum age (years): 15
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Subjects With Human Serum Bactericidal Activity (hSBA)≥1:4
timeFrame: Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).
measure: Percentage of Subjects With hSBA≥1:5
timeFrame: Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).
measure: Percentage of Subjects With hSBA Titers≥1:5 in Parent Studies-V72P10 and V72_41
timeFrame: At one month after last vaccination in parent studies- V72P10 (Month 7) and V72_41 (Month 2)
measure: Percentage of Subjects With hSBA≥1:8
timeFrame: Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).
measure: Percentage of Subjects With hSBA≥1:16
timeFrame: Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).
measure: hSBA Geometric Mean Titers (GMTs) After the Last Dose of rMenB+OMV NZ Vaccination in the Parent Study.
timeFrame: 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)
measure: Geometric Mean Ratios (GMRs) of GMTs After the Last Dose of rMenB+OMV NZ Vaccination in the Parent Study Versus Day 1.
timeFrame: Group 3B: 1 month after the last vaccination in parent study and Day 1 (prior to booster dose)
measure: Number of Subjects With Solicited Local and Systemic AEs.
timeFrame: 7 days (including the day of vaccination) after each vaccination
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs).
timeFrame: 30 days (including the day of vaccination) after each vaccination.
measure: Number of Subjects With Any SAEs, AEs Leading to Withdrawal and Medically Attended AEs.
timeFrame: 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 outcomes:
measure: Percentage of Subjects With hSBA ≥1:4 After Booster Dose/First Vaccination of rMenB+OMV NZ.
timeFrame: Group 3B: 30 days after booster dose, Group B_0_1 : 30 days after first vaccination.
measure: Percentage of Subjects With hSBA ≥1:5 After Booster Dose/First Vaccination of rMenB+OMV NZ.
timeFrame: Group 3B: 30 days after booster dose, Group B_0_1 : 30 days after first vaccination.
measure: Percentage of Subjects With hSBA ≥1:8 After Booster Dose/First Vaccination of rMenB+OMV NZ
timeFrame: Group 3B : 30 days after booster dose, Group B_0_1 : 30 days after first vaccination.
measure: Percentage of Subjects With hSBA ≥1:16 After Booster Dose/First Vaccination of rMenB+OMV NZ
timeFrame: Group 3B: 30 days after booster dose, Group B_0_1 : 30 days after first vaccination.
measure: hSBA Geometric Mean Titers Prior to Booster/First Dose of Vaccination & Post Booster/First Dose of Vaccination.
timeFrame: 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.
measure: Geometric Mean Ratio (GMRs) of GMTs After Booster Dose/First rMenB+OMV NZ Vaccination Versus Day 1.
timeFrame: At Day 31 (30 days post booster dose/first dose of vaccination) versus Day 1 (prior to booster dose/first dose of vaccination).
measure: 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
timeFrame: Group 3B: 1 month after booster dose; Group B_0_1: 1 month after first vaccination
measure: Percentage of Subjects With hSBA ≥1:4 After Booster Dose/Second Vaccination of rMenB+OMV NZ
timeFrame: 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.
measure: Percentage of Subjects With hSBA ≥1:5 After Booster Dose/Second Vaccination of rMenB+OMV NZ
timeFrame: 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."
measure: Percentage of Subjects With hSBA ≥1:8 After Booster Dose/Second Vaccination of rMenB+OMV NZ
timeFrame: 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.
measure: Percentage of Subjects With hSBA ≥1:16 After Booster Dose/Second Vaccination of rMenB+OMV NZ
timeFrame: 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
measure: hSBA Geometric Mean Titers Prior to Booster/Second Dose of Vaccination & Post Booster/Second Dose of Vaccination.
timeFrame: 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.
measure: Geometric Mean Ratios (GMRs) of GMTs After Booster/Second Vaccination Versus Before Booster/Second Vaccination.
timeFrame: 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
measure: 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
timeFrame: 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
measure: Percentage of Subjects With hSBA ≥1:4 After Second Vaccination of rMenB+OMV NZ
timeFrame: At Day 61 (30 days post second dose of vaccination.)
measure: Percentage of Subjects With hSBA ≥1:5 After Second Vaccination of rMenB+OMV NZ
timeFrame: At Day 61 (30 days post second dose of vaccination.)
measure: Percentage of Subjects With hSBA ≥1:8 After Second Vaccination of rMenB+OMV NZ.
timeFrame: At Day 61 (30 days post second vaccination)
measure: Percentage of Subjects With hSBA ≥1:16 After Second Vaccination of rMenB+OMV NZ.
timeFrame: At Day 61 (30 days post second vaccination)
measure: hSBA Geometric Mean Titers (GMTs) After Second Vaccination of rMenB+OMV NZ.
timeFrame: At Day 1 & Day 61 (30 days post second dose of vaccination)
measure: Geometric Mean Ratio (GMRs) of GMTs One Month Post Second Vaccination Versus Pre Vaccination at Day 1
timeFrame: At Day 1 & Day 61 (30 days post 2nd vaccination)
measure: Percentages of Subjects With at Least Four-fold Increase in hSBA Titers at Pre-First Vaccination Compared to One Month Post-Second Vaccination
timeFrame: At Day 61 (30 days post second dose of vaccination)
Other outcomes:
Locations:
city: Sherwood
country: Australia
facility: GSK Investigational Site
state: Queensland
city: North Adelaide
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Carlton
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Subiaco
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Truro
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Newmarket
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sudbury
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Woodstock
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Santiago
country: Chile
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Nolan T, Santolaya ME, de Looze F, Marshall H, Richmond P, Henein S, Rheault P, Heaton K, Perrett KP, Garfield H, Gupta A, Ferguson M, D'Agostino D, Toneatto D, O'Ryan M. Antibody persistence and booster response in adolescents and young adults 4 and 7.5 years after immunization with 4CMenB vaccine. Vaccine. 2019 Feb 21;37(9):1209-1218. doi: 10.1016/j.vaccine.2018.12.059. Epub 2019 Jan 26.