Clinical trial NCT02946385: Study to Assess the Immunological Long-term Persistence of Antibodies (Abs) 2 Years After GlaxoSmithKline (GSK) Meningococcal ABCWY Vaccination in the V102_15 (NCT02212457) and Response to a Booster in Adolescents
Official title: A Phase 2b Open-Label Multi-Center Study Assessing the Immunological Persistence of Antibodies at Approximately 2 Years After the Last Meningococcal Vaccination in Study V102_15 (NCT02212457) and the Response to a Booster Dose of GSK MenABCWY or Meningococcal Serogroup B Vaccines, in Healthy Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infections, Meningococcal
Keywords: meningococcal disease
meningitis
booster
antibody persistence
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-10-27
Enrollment: 604
Sex: ALL
Minimum age (years): 12
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to compare the persistence of 2 or 3 doses of the GSK MenABCWY vaccine, or 2 doses of GSK rMenB+OMV vaccine (Bexsero) administered to healthy adolescents at approximately 24 months after the last meningococcal vaccination in the parent study V102_15(NCT02212457), compared with baseline antibody levels in vaccine naïve subjects at similar age at enrolment.

Detailed description: Naive subjects will be randomized 1:1 to receive MenABCWY or rMenB+OMV at Day 1. No randomization to treatment arm for follow-on subjects is required as vaccine groups remain the same as in the parent study V102_15 (NCT02212457).

Response to a booster dose of MenABCWY vaccine will also be assessed in follow-on subjects who received 2 or 3 doses of MenABCWY (at 0.2-, 0,.6- or 0,.2,.6-month schedules) in the parent study, and will be compared with responses to a single dose of MenABCWY in naive subjects (subjects who are meningococcal vaccine-naive and of similar age to subjects enrolled from the parent study).

Response to a booster dose of GSK Meningococcal B Recombinant vaccine (rMenB+OMV) will be assessed in subjects who received 2 doses of rMenB+OMV (at 0, 2-month schedule) in the parent study, and will be compared with responses to a single dose of rMenB+OMV in naive subjects.

Eligibility criteria: Inclusion Criteria:

Follow-on Participants

* Subjects from Finland and Poland previously enrolled in study V102_15 (NCT02212457) who have received all planned meningococcal vaccinations in the study
* Who have not received any additional meningococcal vaccination since the last meningococcal vaccination administered in the parent trial.
* Who have given written informed consent or assent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. If the subject is under age 18 at the time of enrollment, the parent(s)/ legal guardian(s) of the subject should have given their written consent.
* Individuals of who the investigator believes can and will comply with the requirements of the protocol.
* Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.

Naive Group

* Male and female individuals of similar age (approximately 12-20 years) to follow-on subjects from V102_15 (NCT02212457) trial.
* Who have not received any meningococcal vaccination since birth
* Individuals who have given their written informed consent or assent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. If the subject is under age 18 at the time of enrollment, the parent(s)/ legal guardian(s) of the subject should have given their written consent.
* Individuals of who the investigator believes can and will comply with the requirements of the protocol.
* Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.

Exclusion Criteria:

Follow-on Participants:

* Follow-on individuals not eligible to be enrolled in the study are those with:
* History of any meningococcal vaccine administration since last meningococcal vaccination administered in V102_15 (NCT02212457) parent study.
* Current or previous, confirmed or suspected disease caused by N. meningitidis, since termination from parent study.
* Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days of enrollment.
* If the subject is female of childbearing potential, sexually active, and has not used any of the acceptable contraceptive methods for at least 2 months prior to study entry and for the duration of the trial.
* Pregnancy or breast-feeding
* History of severe allergic reactions after previous vaccinations or hypersensitivity to any vaccine component including diphtheria toxoid (CRM197) and latex.
* Progressive, unstable or uncontrolled clinical conditions.
* Any confirmed or suspected condition with impaired/altered function of immune system.
* Chronic administration of immunosuppressants or other immune-modifying drugs within three months prior to the study vaccination or planned use throughout the study period. (For corticosteroids, this means prednisone, or equivalent, ≥ 20 mg/day. Inhaled, intranasal and topical steroids are allowed).
* Administration of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the 3 months prior to study enrolment.
* Received an investigational or non-registered medicinal product within 30 days prior to informed consent.
* Administration of any vaccine within 14 days or 28 days prior to enrollment in the study, or within 7 days after vaccination in the study.
* Clinical conditions representing a contraindication to intramuscular vaccination and/or blood draws.
* Who have received systemic antibiotic treatment within 3 days prior to any blood draw
* Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study.

Naive Individuals

* Naive individuals not eligible to be enrolled in the study are those with:
* History of any meningococcal vaccine administration since birth.
* Current or previous, confirmed or suspected disease caused by N. meningitidis.
* Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days of enrollment.
* If the subject is female of childbearing potential, sexually active, and has not used any of the acceptable contraceptive methods for at least 2 months prior to study entry and for the duration of the trial.
* Pregnancy or breast-feeding.
* History of severe allergic reactions after previous vaccinations or hypersensitivity to any vaccine component including diphtheria toxoid (CRM197) and latex.
* Progressive, unstable or uncontrolled clinical conditions.
* Any confirmed or suspected condition with impaired/altered function of immune system.
* Chronic administration of immunosuppressants or other immune-modifying drugs within 30 days prior to the study enrolment. (For corticosteroids, this means prednisone, or equivalent, ≥ 20 mg/kg/day. Inhaled, intranasal and topical steroids are allowed).
* Administration of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 3 months or planned use throughout the study period.
* Received an investigational or non-registered medicinal product within 30 days prior to informed consent.
* Individuals who are part of study personnel or close family members conducting this study.
* Administration of any vaccine within 14 days or 28 days prior to enrollment in the study, or within 7 days after first vaccination, and/or planned use of any vaccine 7 days prior to and 7 days after second vaccination.
* Clinical conditions representing a contraindication to intramuscular vaccination and/or blood draws.
* Who have received systemic antibiotic treatment within 3 days prior to any blood draw
* Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study.

Primary outcomes:
measure: Percentages of Subjects With hSBA Titers ≥LLOQ Against 4 Serogroup B Test Strains, and Against N. Meningitidis Serogroups A, C, W and Y at 24 Months After Last Meningococcal Vaccination in Follow-on Subjects in V102_15 and at Day 1 in Naive Subjects
timeFrame: At 24 months after the last meningococcal vaccination for all follow-on subjects and at Day 1 in the extension study for naive subjects
measure: hSBA GMTs Against Each of Four Serogroup B Test Strains, and Against N. Meningitidis Serogroups A, C, W and Y at 24 Months After Last Meningococcal Vaccination in Follow-on Subjects in V102_15 and at Day 1 in Naive Subjects
timeFrame: At 24 months after the last meningococcal vaccination for all follow-on subjects and at Day 1 in the extension study for naive subjects
Secondary outcomes:
measure: Percentages of Subjects With HT-hSBA Titers ≥ LLOQ Against 4 Serogroup B Test Strains, and Against N. Meningitidis Serogroups A, C, W and Y at Day 31 After MenABCWY Vaccination in V102_15E1
timeFrame: Day 31: One month after a booster dose of MenABCWY given at 24 months after last MenABCWY vaccination in groups: ABCWY_0_2, ABCWY_0_6 and ABCWY_0_2_6 and after first dose of MenABCWY in Naive_ABCWY Group
measure: Percentages of Subjects With 4-Fold Increase in HT-hSBA Titers Against 4 Serogroup B Test Strains, and Against N. Meningitidis Serogroups A, C, W and Y at Day 31 After MenABCWY Vaccination in V102_15E1
timeFrame: Day 31: One month after a booster dose of MenABCWY given at 24 months after last MenABCWY vaccination in groups: ABCWY_0_2, ABCWY_0_6 and ABCWY_0_2_6 and after first dose of MenABCWY in Naive_ABCWY Group
measure: hSBA GMTs Against Each of Four Serogroup B Test Strains, and Against N. Meningitidis Serogroups A, C, W and Y at Day 31 After MenABCWY Vaccination in V102_15E1
timeFrame: Day 31: One month after a booster dose of MenABCWY given at 24 months after last MenABCWY vaccination in groups: ABCWY_0_2, ABCWY_0_6 and ABCWY_0_2_6 and after first dose of MenABCWY in Naive_ABCWY Group
measure: Percentages of Subjects With hSBA Titers ≥LLOQ Against 4 Serogroup B Test Strains, and N. Meningitidis Serogroups A, C, W and Y at 24 Months At Days 1, 6, 31 in V102_15 Follow-on Subjects and at Day 1, 66, 91 in Naive Subjects, in MenABCWY Groups
timeFrame: At Day 1, Day 6 and 31(after booster dose of MenABCWY given at 24 months after last MenABCWY vaccination) in ABCWY_0_2, ABCWY_0_6 and ABCWY_0_2_6 groups and at Day 1, Day 66 and 91(i.e. day 6 and 1 month after dose 2 of MenABCWY) in Naive_ABCWY Group
measure: Percentages of Subjects With 4-Fold Increase in HT-hSBA Titers Against 4 Serogroup B Test Strains, and Against N. Meningitidis Serogroups A, C, W and Y At Days 6, 31 in Follow-on Subjects in V102_15 and at Day 66, 91 in Naive Subjects, in MenABCWY Groups
timeFrame: At Day 6 and 31(after booster dose of MenABCWY given at 24 months after last MenABCWY vaccination) in ABCWY_0_2, ABCWY_0_6 and ABCWY_0_2_6 groups and at Day 66 and 91(i.e. day 6 and 1 month after dose 2 of MenABCWY) in Naive_ABCWY Group
measure: hSBA GMTs Against Each of Four Serogroup B Test Strains, and Against N. Meningitidis Serogroups A, C, W and Y At Days 1, 6, 31 in Follow-on Subjects in V102_15 and at Day 1, 66, 91 in Naive Subjects, in MenABCWY Groups
timeFrame: At Day 1, Day 6 and 31(after booster dose of MenABCWY given at 24 months after last MenABCWY vaccination) in ABCWY_0_2, ABCWY_0_6 and ABCWY_0_2_6 groups and at Day 1, Day 66 and 91(i.e. day 6 and 1 month after dose 2 of MenABCWY) in Naive_ABCWY Group
measure: Percentages of Subjects With HT-hSBA Titers ≥ LLOQ Against 4 Serogroup B Test Strains at Day 31 After rMenB+OMV Vaccination in V102_15E1
timeFrame: Day 31: One month after a booster dose of rMenB+OMV given at 24 months after last rMenB+OMVl vaccination in B_0_2 Group and after first dose of rMenB+OMV in Naive_B Group
measure: Percentages of Subjects With 4-Fold Increase in HT-hSBA Titers Against 4 Serogroup B Test Strains at Day 31 After rMenB+OMV Vaccination in V102_15E1
timeFrame: Day 31: One month after a booster dose of rMenB+OMV given at 24 months after last rMenB+OMV vaccination in B_0_2 Group and after first dose of rMenB+OMV in Naive_B Group
measure: hSBA GMTs Against Each of Four Serogroup B Test Strains, at Day 31 After rMenB+OMV Vaccination in V102_15E1
timeFrame: Day 31: One month after a booster dose of rMenB+OMV given at 24 months after last rMenB+OMV vaccination in B_0_2 Group and after first dose of rMenB+OMV in Naive_B Group
measure: Percentages of Subjects With hSBA Titers ≥LLOQ Against 4 Serogroup B Test Strains at 24 Months At Days 1, 6, 31 in Follow-on Subjects in V102_15 and at Day 1, 66, 91 in Naive Subjects, in rMenB+OMV Groups
timeFrame: At Day 1, at Day 6 and 31(after a booster dose of rMenB+OMV given at 24 months after last rMenB+OMV vaccination) in B_0_2 Group, and at Day 1, at Day 66 and 91(i.e. day 6 and 1 month after second dose of rMenB+OMV) in Naive_B Group
measure: Percentages of Subjects With 4-Fold Increase in HT-hSBA Titers Against 4 Serogroup B Test Strains At Days 6, 31 in Follow-on Subjects in V102_15 and at Day 66, 91 in Naive Subjects, in rMenB+OMV Groups
timeFrame: At Day 6 and 31(after a booster dose of rMenB+OMV given at 24 months after last rMenB+OMV vaccination) in B_0_2 Group, and at Day 66 and 91(i.e. day 6 and 1 month after second dose of rMenB+OMV) in Naive_B Group
measure: hSBA GMTs Against Each of Four Serogroup B Test Strains At Days 1, 6, 31 in Follow-on Subjects in V102_15 and at Day 1, 66, 91 in Naive Subjects, in rMenB+OMV Groups
timeFrame: At Day 1, at Day 6 and 31(after a booster dose of rMenB+OMV given at 24 months after last rMenB+OMV vaccination) in B_0_2 Group, and at Day 1, at Day 66 and 91(i.e. day 6 and 1 month after second dose of rMenB+OMV) in Naive_B Group
measure: Number of Subjects With Any Solicited Local or Systemic AEs and Other Indicators of Reactogenicity Within 30 Minutes After Vaccination
timeFrame: within 30 minutes after vaccination at Day 1 (for all subjects) and also Day 61 (for naive subjects only)
measure: Number of Subjects With Any Unsolicited AEs Within 30 Minutes After Vaccination
timeFrame: Within 30 minutes after vaccination at Day 1 (for all subjects) and also Day 61 (for naive subjects only)
measure: Number of Subjects With Any Solicited Local or Systemic Adverse Events (AEs) and Other Indicators of Reactogenicity From Day 1 to Day 7.
timeFrame: At Day 1 (6 hours) to Day 7 after vaccination at Day 1 (for all subjects) and Day 61 to Day 67 (for naive subjects only)
measure: Number of Subjects With Unsolicited AEs, 30 Days After Any Vaccination
timeFrame: From Day 1 to Day 31 for all subjects and Day 61 to Day 91 for naive subjects
measure: Number of Subjects With Any Serious AE (SAE), Medically Attended AEs (MAAEs), AEs Leading to Premature Withdrawal
timeFrame: During the entire study period (up to Day 181 for follow-on subjects and up to Day 241 for naive subjects)
Other outcomes:
Locations:
city: Espoo
country: Finland
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Jarvenpaa
country: Finland
facility: GSK Investigational Site
city: Kokkola
country: Finland
facility: GSK Investigational Site
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Pori
country: Finland
facility: GSK Investigational Site
city: Seinajoki
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Debica
country: Poland
facility: GSK Investigational Site
city: Gdansk
country: Poland
facility: GSK Investigational Site
city: Gdansk
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Siemianowice Slaskie
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: