Safety, Tolerability, and Immunogenicity of MenABCWY Administered on Different Dosing Schedules in Healthy Adolescents

• ClinicalTrials.gov Identifier: NCT05087056
• Recruitment Status: Active, not recruiting
• First Posted: October 21, 2021
• Last Update Posted: January 25, 2023
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

The purpose of this study is to assess the safety, tolerability, and immunogenicity of the combined meningococcal groups A, B, C, W and Y (MenABCWY) vaccine (GSK3536819A) intended to protect against invasive meningococcal disease (IMD) caused by all 5 meningococcal serogroups.

Condition or disease	Intervention/treatment	Phase
Meningitis, Meningococcal	Combination Product: MenABCWY vaccine; Combination Product: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Observer-blind study. Participants and study evaluators will be unaware of vaccine administered.
• Primary Purpose: Prevention
• Official Title: A Phase IIb, Randomized, Observer-Blind Study to Describe the Safety, Tolerability, and Immunogenicity of MenABCWY Administered on Different Dosing Schedules in Healthy Adolescents
• Actual Study Start Date: December 29, 2021
• Estimated Primary Completion Date: February 26, 2027
• Estimated Study Completion Date: February 26, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: ABCWY-24 Group; Participants receive 2 doses of the MenABCWY vaccine at Day 1 and Day 721, 1 dose of Placebo at Day 1441.	Combination Product: MenABCWY vaccine; Two doses of the MenABCWY vaccine, administered intramuscularly in the deltoid region of the non-dominant arm, on a 0-, 24-month schedule in the ABCWY-24 Group, and a 0-, 48-month schedule in the ABCWY-48 Group.; Combination Product: Placebo; Single dose of Placebo (saline solution in pre-filled syringe), administered intramuscularly in the deltoid region of the non-dominant arm, at Day 1441 in the ABCWY-24 Group, and at Day 721 in the ABCWY-48 Group.
Experimental: ABCWY-48 Group; Participants receive 2 doses of the MenABCWY vaccine at Day 1 and Day 1441, 1 dose of Placebo at Day 721.	Combination Product: MenABCWY vaccine; Two doses of the MenABCWY vaccine, administered intramuscularly in the deltoid region of the non-dominant arm, on a 0-, 24-month schedule in the ABCWY-24 Group, and a 0-, 48-month schedule in the ABCWY-48 Group.; Combination Product: Placebo; Single dose of Placebo (saline solution in pre-filled syringe), administered intramuscularly in the deltoid region of the non-dominant arm, at Day 1441 in the ABCWY-24 Group, and at Day 721 in the ABCWY-48 Group.

Outcome Measures

Primary Outcome Measures :

1. Percentage of participants with human serum bactericidal assay (hSBA) titers ≥ lower limit of quantitation (LLOQ) for each N. meningitidis serogroup B indicator strains [ Time Frame: At Baseline (Day 1) ]
   The immune response to 2 doses of the MenABCWY vaccine administered on a 0-, 24-month schedule, and a 0-, 48-month schedule is evaluated against each N. meningitidis serogroup B indicator strains.
2. Percentage of participants with hSBA titers ≥ LLOQ for each N. meningitidis serogroup B indicator strains [ Time Frame: At 1 month after the second dose of MenABCWY (Day 751 for the ABCWY-24 Group and Day 1471 for the ABCWY-48 Group) ]
   The immune response to 2 doses of the MenABCWY vaccine administered on a 0-, 24-month schedule, and a 0-, 48-month schedule is evaluated against each N. meningitidis serogroup B indicator strains.
3. Percentage of participants with solicited administration site events [ Time Frame: During the 7 days (including the day of vaccination) following each vaccination (Vaccines administered at Day 1, Day 721 and Day 1441) ]
   The solicited administration site events include pain, redness, swelling and induration. Redness, swelling, and induration are summarized according to defined severity grading scales: None (0 to 24mm); Mild (25 to 50mm); Moderate (51 to 100mm); Severe (>100mm). Injection site pain is summarized according to "mild", "moderate" or "severe".
4. Percentage of participants with solicited systemic events [ Time Frame: During the 7 days (including the day of vaccination) following each vaccination (Vaccines administered at Day 1, Day 721 and Day 1441) ]
   The solicited systemic events include fever, headache, nausea, myalgia, arthralgia and fatigue. Fever is defined as body temperature 38.0°C (100.4°F). The preferred location for measuring temperature in this study is the oral route. Solicited systemic events (except fever) are summarized according to "mild", "moderate" or "severe".
5. Percentage of participants with any unsolicited adverse events (AEs) including all serious adverse events (SAEs), AEs leading to withdrawal, adverse events of special interest (AESIs) and medically attended AEs [ Time Frame: During the 30 days (including the day of vaccination) following each vaccination (Vaccines administered at Day 1, Day 721 and Day 1441) ]
   An unsolicited AE is an AE that was not included in a list of solicited events and must have been spontaneously communicated by a participant/participant's parent(s)/ Legally Acceptable Representative(s) who has signed the informed consent. An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject or is an abnormal pregnancy outcome. AESIs are predefined 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 in order to characterise and understand it. Medically attended AEs are symptoms or illnesses requiring a hospitalisation, or an emergency room visit, or visit to/by a health care provider.
6. Percentage of participants with SAEs, AEs leading to withdrawal, AESIs and medically attended AEs [ Time Frame: During the 6 months (including the day of vaccination) following the first vaccination (Vaccine administered at Day 1) ]
   An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject or is an abnormal pregnancy outcome. 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 in order to characterise and understand it. Medically attended AEs are symptoms or illnesses requiring a hospitalisation, or an emergency room visit, or visit to/by a health care provider.
7. Percentage of participants with SAEs, AEs leading to withdrawal, AESIs and medically attended AEs [ Time Frame: During the 6 months (including the day of vaccination) following the second vaccination (Vaccine administered at Day 721) ]
   An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject or is an abnormal pregnancy outcome. 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 in order to characterise and understand it. Medically attended AEs are symptoms or illnesses requiring a hospitalisation, or an emergency room visit, or visit to/by a health care provider.

Secondary Outcome Measures :

1. Percentage of participants with hSBA titers ≥ LLOQ for N. meningitidis serogroups A, C, W and Y [ Time Frame: At Baseline (Day 1), 1 month after the first dose of MenABCWY (Day 31) and 1 month after second dose of MenABCWY (Day 751 for the ABCWY-24 Group and Day 1471 for the ABCWY-48 Group) ]
   The immune response to 1 and 2 doses of the MenABCWY vaccine administered on a 0-, 24-month schedule, and a 0-, 48-month schedule is evaluated against N. meningitidis serogroups A, C, W and Y.
2. Percentage of participants with hSBA titers ≥ LLOQ for each N. meningitidis serogroup B indicator strains and for serogroups A, C, W and Y [ Time Frame: At 25 months after the second dose of MenABCWY (Day 1471 for the ABCWY-24 Group) ]
   The antibody persistence at 25 months after the second dose of the MenABCWY vaccine administered on a 0-, 24-month schedule is evaluated against each N. meningitidis serogroup B indicator strains and serogroups A, C, W and Y.

Eligibility Criteria

• Ages Eligible for Study: 11 Years to 14 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Participants or/and participants' 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 participant/parent(s)/LAR(s) of the participant prior to performance of any study specific procedure.
• Written informed assent obtained from the participant (if applicable) prior to performing any study specific procedure.
• A male or female between, and including, 11 and 14 years of age (i.e. 14 years + 364 days) at the time of the first vaccination.
• Healthy participants as established by medical history, physical examination and clinical judgment of the investigator before entering into the study.
• Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, hysterectomy, bilateral-salpingectomy or bilateral ovariectomy.

• Female participants of childbearing potential may be enrolled in the study, if the participant:

  • has practiced adequate contraception for 30 days prior to first vaccination, and
  • has a negative pregnancy test* on the day of vaccination, and
  • has agreed to follow adequate contraception for 30 days before each of the 2 subsequent vaccinations and for 30 days after each vaccination * Urine samples for pregnancy testing will be collected from female participants of childbearing potential at Visit 1, Visit 3 and Visit 5 prior to the vaccination.

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 (CRM197) 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. This will mean prednisone equivalent ≥20 mg/day for adult participants / ≥0.5 mg/kg/day with maximum 20 mg/day for paediatric participants. 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.
• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.

Prior/Concomitant therapy

• Use of any investigational or non-registered product (drug, vaccine or medical device) 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 with any meningococcal (MenB or MenACWY) vaccine at any time prior to informed consent/ assent (as applicable) with the exception of meningococcal C (conjugated or polysaccharide) vaccination, if the last dose of MenC was received at ≤24 months of age.
• Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the administration of study vaccine/product or planned administration before the next blood sampling visit.
• 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 first vaccine/product dose(s). For corticosteroids, this will mean prednisone equivalent ≥20 mg/day for adult participants / ≥0.5 mg/kg/day with maximum of 20 mg/day for paediatric participants. 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 participant has been or will be exposed to an investigational or a non-investigational vaccine/product (drug or medical device).

Other exclusions

• Child in care.
• Pregnant or lactating female.
• Female planning to become pregnant / planning to discontinue contraceptive precautions during the windows reported in the inclusion criterion.
• History of /current chronic alcohol abuse and/or drug abuse as determined by the investigator.
• Any study personnel or immediate dependants, family, or household members.

Contacts and Locations

Locations

United States, Alabama

GSK Investigational Site

Birmingham, Alabama, United States, 35205

United States, Colorado

GSK Investigational Site

Grand Junction, Colorado, United States, 80216

United States, District of Columbia

GSK Investigational Site

Washington, District of Columbia, United States, 20016

United States, Florida

GSK Investigational Site

Miami, Florida, United States, 33156

GSK Investigational Site

Miami, Florida, United States, 33174

United States, Georgia

GSK Investigational Site

Macon, Georgia, United States, 31210

United States, Kentucky

GSK Investigational Site

Lexington, Kentucky, United States, 40503

United States, Louisiana

GSK Investigational Site

Haughton, Louisiana, United States, 71037

United States, Montana

GSK Investigational Site

Missoula, Montana, United States, 59804

United States, Nebraska

GSK Investigational Site

Hastings, Nebraska, United States, 68901

GSK Investigational Site

Lincoln, Nebraska, United States, 68510

GSK Investigational Site

Omaha, Nebraska, United States, 68134

United States, New York

GSK Investigational Site

Binghamton, New York, United States, 13901

GSK Investigational Site

Endwell, New York, United States, 13760

United States, North Carolina

GSK Investigational Site

Charlotte, North Carolina, United States, 28226

United States, Oregon

GSK Investigational Site

Gresham, Oregon, United States, 97030

United States, South Carolina

GSK Investigational Site

Charleston, South Carolina, United States, 29414

United States, Tennessee

GSK Investigational Site

Kingsport, Tennessee, United States, 37660

United States, Texas

GSK Investigational Site

Galveston, Texas, United States, 77555 1115

GSK Investigational Site

Plano, Texas, United States, 75024

United States, Utah

GSK Investigational Site

Kaysville, Utah, United States, 84037

Germany

GSK Investigational Site

Mannheim, Baden-Wuerttemberg, Germany, 68161

GSK Investigational Site

Schoenau Am Koenigssee, Bayern, Germany, 83471

GSK Investigational Site

Leipzig, Brandenburg, Germany, 16269

GSK Investigational Site

Herxheim, Rheinland-Pfalz, Germany, 76863

GSK Investigational Site

Bramsche, Germany, 49565

GSK Investigational Site

Schweigen-Rechtenbach, Germany, 76889

Sponsors and Collaborators

GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT05087056
• Other Study ID Numbers: 215344; 2021-001670-33 ( EudraCT Number )
• First Posted: October 21, 2021
• Last Update Posted: January 25, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

MenABCWY; Safety; Tolerability; Immunogenicity; Healthy adolescents; Invasive meningococcal disease

Additional relevant MeSH terms:

Meningitis, Meningococcal; Meningitis; Central Nervous System Diseases; Nervous System Diseases; 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