A Study on the Safety, Effectiveness and Immune Response of Meningococcal Combined ABCWY Vaccine in Healthy Adolescents and Adults

A Phase I/II, Randomised, Controlled Study to Assess the Safety, Effectiveness and Immune Response of Meningococcal Combined ABCWY Vaccine When Administered to Healthy Adults (Phase I) and to Healthy Adolescents and Adults (Phase II)

The purpose of this study was to assess the safety, effectiveness, and immune response of the meningococcal combined ABCWY vaccine (GSK4023393A) intended to protect against invasive meningococcal disease (IMD) caused by all 5 meningococcal serogroups. The first time-in-human (FTIH), Phase I part of this study was conducted in healthy adults in a dose-escalating fashion with 2 formulations of the investigational MenABCWY-2Gen vaccine and served as a safety lead-in to the Phase II study. The Phase II part of the study was conducted in 2 parts: The 'formulation and schedule-finding' part followed in healthy adolescents and young adults and was designed to select the vaccine formulation and the schedule to be tested in Phase III. The 'blood sourcing' part was conducted in healthy adults in order to collect sufficient serum samples for the development of assays to be used in the MenABCWY-2Gen vaccine clinical development program.

Inclusion Criteria:

All inclusion criteria are applicable for both study phases, except where specified otherwise.

• Participants and/or participants' parent(s)/Legally Acceptable Representative(s) (LAR) who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the eDiaries, return for follow-up visits).

• Written or witnessed/thumb printed informed consent obtained from the participant or /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.

• Phase I only: A male or female between, and including, 18 and 40 years of age (i.e. 40 years + 364 days) at the time of the first study intervention administration.

• Phase II (Formulation and Schedule-finding) only: A male or female between, and including, 10 and 25 years of age (i.e. 25 years + 364 days) at the time of the first study intervention administration.

• Phase II (Sourcing) only: A male or female between, and including, 18 and 50 years of age (i.e. 50 years + 364 days) at the time of the first study intervention administration.

• Participants who are either unvaccinated with MenACWY vaccine or have received a single previous dose of MenACWY vaccine can participate in the study, if they have received it at least 4 years prior to informed consent and assent as applicable (with the exception of meningococcal C vaccination, if the last dose of MenC was received at ≤24 months of age).

• Healthy participants as established by medical history and clinical examination 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, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.

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

  • has practiced adequate contraception for 1 month prior to study intervention administration, and
  • has a negative pregnancy test on the day of study intervention administration, and
  • has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the study intervention administration.

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.

• Are obese at enrolment (e.g. for participants from 20 years of age a body mass index (BMI) ≥ 30 kg/m2, for participants up to 19 years of age a BMI ≥ 95th percentile for age and gender or as applicable per country recommendations).

• Any neuroinflammatory (including but not limited to: demyelinating disorders, encephalitis or myelitis of any origin), congenital neurological conditions, encephalopathies, seizures (including all subtypes such as: absence seizures, generalised tonic-clonic seizures, partial complex seizures, partial simple 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 study interventions.

• 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 (including, but not limited to: blood, endocrine, hepatic, muscular, nervous system or skin autoimmune disorders; lupus erythematosus and associated conditions; rheumatoid arthritis and associated conditions; scleroderma and associated disorders) or immunodeficiency syndromes (including, but not limited to: acquired immunodeficiency syndromes and primary immunodeficiency syndromes).
  • Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 3 months prior to study vaccination until the last blood sampling visit for Phase I and Phase II (Sourcing) and Visit 5 (Day 211) for Phase II (Formulation and Schedule-finding). 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.
  • 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 (e.g. infliximab).

• 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 intervention(s) during the period beginning 30 days before the first dose of study intervention(s) (Day -29 to Day 1), or their planned use during the study period.
• Previous vaccination against any group B meningococcal vaccine at any time prior to informed consent and assent as applicable.
• Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the administration of the first dose of study intervention(s) or planned administration until the last blood sampling visit for Phase I and Phase II (Sourcing) and Visit 5 (Day 211) for Phase II (Formulation and Schedule-finding).
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first study intervention dose(s) until the last blood sampling visit for Phase I and Phase II (Sourcing) and Visit 5 (Day 211) for Phase II (Formulation and Schedule-finding). 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 intervention (drug/invasive medical device).

Other exclusions

• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.
• History of /current chronic alcohol abuse and/or drug abuse as determined by the investigator.
• Any study personnel or immediate dependents, family, or household member.
• Phase II (Formulation and Schedule-finding): Child in care.