Study to Assess Potential Immune Interference When GlaxoSmithKline (GSK) Biologicals' MenABCWY Vaccine is Administered to Healthy Subjects Aged 10-25 Years

NCT03587207 | Completed Phase 2 Results

• 2 other identifiers: 2082052017-005128-12
• Study Type: interventional
• Target: 520
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the current study is to evaluate whether there is immune interference when MenABCWY \[consisting of MenACWY lyophilized component and rMenB+OMV NZ (Bexsero) liquid component\] is administered to healthy adolescents and adults following a 2-dose vaccination schedule with MenABCWY administered 2 months apart.

Conditions

Meningitis, Meningococcal

Keywords

Meningitis; Concomitantly; Adolescent; Neisseria meningitidis; Healthy subjects; Adult

Outcome Measures

Primary Outcomes (5)

• Human Serum Bactericidal Activity (hSBA) Adjusted Geometric Mean Titers (GMTs) Against All of N. Meningitidis Serogroup B Test Strains (Pooled), One Month After Last Vaccination.

  hSBA titers against all of N. meningitidis serogroup B test strains were calculated in terms of GMTs. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). The serogroup B strains were grouped together to perform a pooled analysis. Adjusted means were obtained from ANCOVA model fitted to all of the Serogroup B test strains, study group, test strain and center as fixed effects; zero-centered pre-vaccination log-transformed titer was included as a continuous covariate.

  1 month after last vaccination i.e.: at Day 91 for all groups except for the MenACWY Group

• hSBA Adjusted GMTs Against Each of the N. Meningitidis Serogroup B Test Strains and N. Meningitidis Serogroups A, C, W-135, and Y, One Month After Last Vaccination.

  hSBA titers against each of the N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y were calculated in terms of GMTs. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). Adjusted means were obtained from ANCOVA model fitted to each Serogroup (Strain) individually, study group and center as fixed effects and zero-centered pre-vaccination log-transformed titer as a continuous covariate.

  1 month after last vaccination i.e.: at Day 91 for all groups except the MenACWY Group, and at Day 31 for the MenACWY Group.

• Percentage of Subjects With hSBA Titers Greater Than or Equal to(≥) the Lower Limit of Quantitation (LLOQ) Against Each of the N. Meningitidis Serogroup B Test Strains and Serogroups A, C, W-135 and Y,One Month After Last Vaccination.

  Immune responses against N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, were calculated in terms of percentage of subjects with hSBA titers ≥ LLOQ. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA).

  1 month after last vaccination i.e.: at Day 91 for all groups except the MenACWY Group, and at Day 31 for the MenACWY Group.

• Percentage of Subjects With a 4-fold Increase in hSBA Titers Against Each of the N. Meningitidis Serogroup B Test Strains and Against N. Meningitidis Serogroups A, C, W-135 and Y, One Month After Last Vaccination.

  Immune responses against N. meningitidis serogroup B test strains and N. meningitidis serogroups A, C, W-135, and Y, were calculated in terms of percentage of subjects with a 4-fold increase in hSBA titers. A 4-fold rise was defined as: a) for individuals whose pre-vaccination titers were less than (\<) the limit of detection (LOD), the post-vaccination titers must have been ≥4-fold the LOD or ≥ the LLOQ, whichever was greater; b) for individuals whose pre-vaccination titers were ≥ the LOD and less than (\<) the LLOQ, the post-vaccination titers must have been at least 4 times the LLOQ; and c) for individuals whose pre-vaccination titers were ≥ the LLOQ, the post-vaccination titers must have been at least 4 times the pre-vaccination titer. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA).

  1 month after last vaccination versus baseline (i.e.: at Day 91 versus Day 1 for all groups except the MenACWY Group, and at Day 31 versus Day 1 for the MenACWY Group).

• hSBA Adjusted Geometric Mean Ratios (GMRs) Against Each of the N. Meningitidis Serogroup B Test Strains and Against N. Meningitidis Serogroups A, C, W-135 and Y, One Month After Last Vaccination.

  hSBA mean ratios at 1 month after the last vaccination versus baseline were calculated in terms of GMRs i.e. as the anti-logarithm of the mean of the change from baseline of log-transformed titer values at 1 month after last vaccination and Baseline. Serogroup B strains tested were M14459 (factor H binding protein; fHbp), 96217 (Neisserial adhesin A; NadA), NZ98/254 (PorA), and M070241084 (Neisseria heparin binding antigen; NHBA). Adjusted means were obtained from ANCOVA model fitted to each Serogroup (Strain) individually, study group and center as fixed effects and zero-centered pre-vaccination log-transformed titer as a continuous covariate.

  1 month after last vaccination versus baseline (i.e.: at Day 91 versus Day 1 for all groups except the MenACWY Group, and at Day 31 versus Day 1 for the MenACWY Group).

Secondary Outcomes (9)

• hSBA Adjusted GMTs Against All of N. Meningitidis Serogroup B Test Strains (Pooled), One Month After First Vaccination

  1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group

• hSBA Adjusted GMTs Against Each of the N. Meningitidis Serogroup B Test Strains and N. Meningitidis Serogroups A, C, W-135 and Y, One Month After First Vaccination.

  1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group.

• Percentage of Subjects With hSBA Titers Greater Than or Equal to (≥) the LLOQ Against Each of the N. Meningitidis Serogroup B Test Strains and Against Serogroups A, C, W-135, and Y, One Month After First Vaccination

  1 month after first vaccination i.e.: at Day 31 for all groups except for the MenACWY Group

• Percentage of Subjects With a 4-fold Increase in hSBA Titers Against Each of the N. Meningitidis Serogroup B Test Strains and Against N. Meningitidis Serogroups A, C, W-135, and Y, One Month After First Vaccination

  1 month after first vaccination versus baseline (i.e.: at Day 31 versus Day 1 for all groups except for the MenACWY Group)

• hSBA Adjusted GMRs Against Each of the N. Meningitidis Serogroup B Test Strains and Against N. Meningitidis Serogroups A, C, W-135, and Y, One Month After First Vaccination

  1 month after first vaccination versus baseline (i.e.: at Day 31 versus Day 1 for all groups except for the MenACWY Group)

Study Arms (5)

MenABCWY Group

EXPERIMENTAL

Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of MenABCWY twice, 2 months apart (Day 1 and Day 61).

Biological: MenABCWY vaccine

rMenBOMV+ACWY_S Group

ACTIVE COMPARATOR

Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) concomitantly received one dose of rMenB+OMV NZ (Bexsero) and one dose of MenACWY (Menveo) in the same arm twice, 2 months apart (Day 1 and Day 61).

Biological: rMenB+OMV NZ (Bexsero) vaccine; Biological: MenACWY (Menveo) vaccine

rMenBOMV+ACWY_D Group

ACTIVE COMPARATOR

Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) concomitantly received one dose of rMenB+OMV NZ (Bexsero) and one dose of MenACWY (Menveo) in 2 different arms twice, 2 months apart (Day 1 and Day 61).

Biological: rMenB+OMV NZ (Bexsero) vaccine; Biological: MenACWY (Menveo) vaccine

rMenBOMV Group

ACTIVE COMPARATOR

Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of rMenB+OMV NZ (Bexsero) twice, 2 months apart (Day 1 and Day 61).

Biological: rMenB+OMV NZ (Bexsero) vaccine

MenACWY Group

ACTIVE COMPARATOR

Healthy subjects between, and including, 10 to 25 years of age at the time of the first vaccination (equally distributed across the 2 age strata of 10 to 17 years and 18 to 25 years) received one dose of MenACWY (Menveo) once at Day 1, which was the first and last vaccination for MenACWY group.

Biological: MenACWY (Menveo) vaccine

Interventions

MenABCWY vaccine BIOLOGICAL

Two doses administered intramuscularly in the deltoid region of the non-dominant arm.

MenABCWY Group

rMenB+OMV NZ (Bexsero) vaccine BIOLOGICAL

Two doses administered 2 months apart intramuscularly in the deltoid region of the non-dominant arm to subjects randomised to the rMenBOMV+ACWY\_S Group, rMenBOMV+ACWY\_D Group and rMenBOMV Group

rMenBOMV Group; rMenBOMV+ACWY_D Group; rMenBOMV+ACWY_S Group

MenACWY (Menveo) vaccine BIOLOGICAL

Two doses administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomised to the rMenBOMV+ACWY\_S Group and rMenBOMV+ACWY\_D Group and one dose administered intramuscularly in the deltoid region of the dominant/non-dominant arm to subjects randomised to the MenACWY Group

MenACWY Group; rMenBOMV+ACWY_D Group; rMenBOMV+ACWY_S Group

Eligibility Criteria

• Age: 10 Years - 25 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects and/or subjects' parent(s)/Legally Acceptable Representative(s) (LARs) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol (e.g. completion of the paper diary (pDiary), return for follow-up visits, availability for all visits scheduled in the study).
• Written informed consent obtained from the subject and/or from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure.
• Written informed assent obtained from subjects below the legal age of consent prior to performing any study specific procedure.
• A male or female between, and including, 10 to 25 years of age at the time of the first vaccination.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• 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, or bilateral ovariectomy.
• Female subjects of childbearing potential may be enrolled in the study, if the subject:
• has practiced highly effective contraception for 30 days prior to vaccination, and
• has a negative pregnancy test on the day of vaccination, and
• has agreed to continue highly effective contraception during the entire treatment period and for 2 months after completion of the vaccination series.

You may not qualify if:

• Female planning to become pregnant or planning to discontinue contraceptive precautions
• Pregnant or lactating female
• Child in care
• Current or previous, confirmed or suspected disease caused by N. meningitidis.
• Known contact to an individual with any laboratory confirmed N. meningitidis infection within 60 days prior to enrolment.
• Previous vaccination against N. meningitidis at any time prior to informed consent.
• Progressive, unstable or uncontrolled clinical conditions.
• Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.
• Clinical conditions representing a contraindication to IM vaccination and blood draws.
• Abnormal function of the immune system resulting from:
• Clinical conditions.
• Systemic administration of corticosteroids (oral/intravenous/IM) for more than 14 consecutive days within 90 days prior to informed consent.
• Administration of antineoplastic and immune modulating agents or radiotherapy within 90 days prior to informed consent.
• Received immunoglobulins or any blood products within 180 days prior to informed consent.
• Received an investigational or non registered medicinal product within 30 days prior to informed consent.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Hradec Králové, 50002, Czechia

Location

Related Publications (1)

• Beran J, Drazan D, Enweonye I, Bhusal C, Toneatto D. Immunogenicity and Safety of Investigational MenABCWY Vaccine and of 4CMenB and MenACWY Vaccines Administered Concomitantly or Alone: a Phase 2 Randomized Study of Adolescents and Young Adults. mSphere. 2021 Dec 22;6(6):e0055321. doi: 10.1128/mSphere.00553-21. Epub 2021 Nov 17.

  PMID: 34787449 DERIVED

MeSH Terms

Conditions

Meningitis, Meningococcal; Meningitis

Interventions

4CMenB vaccine; Vaccines; MenACWY; Meningococcal Vaccines

Condition Hierarchy (Ancestors)

Meningitis, Bacterial; Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Meningococcal Infections; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures; Bacterial Vaccines

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2018
• First Posted: July 16, 2018
• Study Start: July 9, 2018
• Primary Completion: December 19, 2018
• Study Completion: December 19, 2018
• Last Updated: February 12, 2020
• Results First Posted: January 2, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

CZ (1)