Clinical trial NCT04886154: A Study on the Safety, Effectiveness and Immune Response of Meningococcal Combined ABCWY Vaccine in Healthy Adolescents and Adults
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Infections, Meningococcal
Keywords: Bexsero
Menveo
Boostrix
MenABCWY-2Gen
Effectiveness
Safety
Invasive Meningococcal Disease
Adolescents and Adults
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2021-05-13
Enrollment: 1440
Sex: ALL
Minimum age (years): 10
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Solicited Administration Site Events in Study Phase I (Safety Lead-in)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 1
measure: Number of Participants With Solicited Administration Site Events in Study Phase I (Safety Lead-in)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 31
measure: Number of Participants With Solicited Systemic Events in Study Phase I (Safety Lead-in)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 1
measure: Number of Participants With Solicited Systemic Events in Study Phase I (Safety Lead-in)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 31
measure: Number of Participants With Any Unsolicited Adverse Events (AEs), Including All Serious Adverse Events (SAEs), AEs Leading to Withdrawal and AEs of Special Interest (AESIs) in Study Phase I (Safety Lead-in)
timeFrame: During the 30 days (including the day of vaccination) following vaccination at Day 1
measure: Number of Participants With Any Unsolicited AEs, Including All SAEs, AEs Leading to Withdrawal and AESIs in Study Phase I (Safety Lead-in)
timeFrame: During the 30 days (including the day of vaccination) following vaccination at Day 31
measure: Number of Participants With SAEs, AEs Leading to Withdrawal and AESIs in Study Phase I (Safety Lead-in)
timeFrame: Throughout the Phase 1 study period (Day 1 through Day 211)
measure: Number of Participants With Change From Baseline in Haematological and Biochemical Laboratory Values, in Study Phase I (Safety Lead-in)
timeFrame: At Day 8 (7 days after the first vaccination)
measure: Number of Participants With Clinically Significant Haematological and Biochemical Laboratory Values, in Study Phase I (Safety Lead-in)
timeFrame: At Day 8 (7 days after the first vaccination)
measure: Percentage of Blood Samples With Bactericidal Serum Activity Using Enc-hSBA Against a Panel of 110 Randomly Selected Endemic US N. Meningitidis Serogroup B Invasive Disease Strains at Study Phase II (Formulation and Schedule-finding)
timeFrame: At Day 211 (1 month after the last vaccination)
measure: Number of Participants With a 4-fold Rise in hSBA Titers Against Serogroups A, C, W and Y in Study Phase II (Formulation and Schedule-finding)
timeFrame: At Day 211 for ABCWY groups (1 month after the last MenABCWY-2Gen vaccination) and at Day 31 for Control group (1 month after the last MenACWY vaccination)
measure: Number of Participants With Solicited Administration Site Events in Study Phase II (Formulation and Schedule-finding)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 1
measure: Number of Participants With Solicited Administration Site Events in Study Phase II (Formulation and Schedule-finding)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 121
measure: Number of Participants With Solicited Administration Site Events in Study Phase II (Formulation and Schedule-finding)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 181
measure: Number of Participants With Solicited Systemic Events in Study Phase II (Formulation and Schedule-finding)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 1
measure: Number of Participants With Solicited Systemic Events in Study Phase II (Formulation and Schedule-finding)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 121
measure: Number of Participants With Solicited Systemic Events in Study Phase II (Formulation and Schedule-finding)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 181
measure: Number of Participants With Any Unsolicited AEs (Including All SAEs, AEs Leading to Withdrawal, and AESIs) in Study Phase II (Formulation and Schedule-finding)
timeFrame: During the 30 days (including the day of vaccination) following vaccination at Day 1
measure: Number of Participants With Any Unsolicited AEs (Including All SAEs, AEs Leading to Withdrawal, and AESIs) in Study Phase II (Formulation and Schedule-finding)
timeFrame: During the 30 days (including the day of vaccination) following vaccination at Day 121
measure: Number of Participants With Any Unsolicited AEs (Including All SAEs, AEs Leading to Withdrawal, and AESIs) in Study Phase II (Formulation and Schedule-finding)
timeFrame: During the 30 days (including the day of vaccination) following vaccination at Day 181
measure: Number of Participants With SAEs, AEs Leading to Withdrawal and AESIs in Study Phase II (Formulation and Schedule-Finding)
timeFrame: Throughout the Phase II FSF study period (Day 1 through Day 541)
measure: Number of Participants With Solicited Administration Site Events in Study Phase II (Sourcing)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 1
measure: Number of Participants With Solicited Administration Site Events in Study Phase II (Sourcing)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 31
measure: Number of Participants With Solicited Administration Site Events in Study Phase II (Sourcing)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 61
measure: Number of Participants With Solicited Administration Site Events in Study Phase II (Sourcing)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 181
measure: Number of Participants With Solicited Systemic Events in Study Phase II (Sourcing)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 1
measure: Number of Participants With Solicited Systemic Events in Study Phase II (Sourcing)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 31
measure: Number of Participants With Solicited Systemic Events in Study Phase II (Sourcing)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 61
measure: Number of Participants With Solicited Systemic Events in Study Phase II (Sourcing)
timeFrame: During the 7 days (including the day of vaccination) following vaccination at Day 181
measure: Number of Participants With Any Unsolicited AEs (Including All SAEs, AEs Leading to Withdrawal, and AESIs) in Study Phase II (Sourcing)
timeFrame: During the 30 days (including the day of vaccination) following vaccination at Day 1
measure: Number of Participants With Any Unsolicited AEs (Including All SAEs, AEs Leading to Withdrawal, and AESIs) in Study Phase II (Sourcing)
timeFrame: During the 30 days (including the day of vaccination) following vaccination at Day 31
measure: Number of Participants With Any Unsolicited AEs (Including All SAEs, AEs Leading to Withdrawal, and AESIs) in Study Phase II (Sourcing)
timeFrame: During the 30 days (including the day of vaccination) following vaccination at Day 61
measure: Number of Participants With Any Unsolicited AEs (Including All SAEs, AEs Leading to Withdrawal, and AESIs) in Study Phase II (Sourcing)
timeFrame: During the 30 days (including the day of vaccination) following vaccination at Day 181
measure: Number of Participants With SAEs, AEs Leading to Withdrawal and AESIs in Study Phase II (Sourcing)
timeFrame: Throughout the study period (Day 1 through Day 211)
measure: Number of Participants With SAEs, AEs Leading to Withdrawal and AESIs in Study Phase II (Sourcing)
timeFrame: Throughout the study period (Day 1 through Day 241)
measure: Number of Participants With SAEs, AEs Leading to Withdrawal and AESIs in Study Phase II (Sourcing)
timeFrame: Throughout the study period (Day 1 through Day 361)
Secondary outcomes:
measure: Percentage of Participants Classified by Percentages of Serogroup B Invasive Disease Strains Killed Using Enc-hSBA in Each Participant in Study Phase II (Formulation and Schedule-finding)
timeFrame: At Day 211 (1 month after the last vaccination)
measure: Number of Participants With hSBA Titers ≥ LLOQ for Each and All Serogroup B Indicator Strains in Study Phase II (Formulation and Schedule-finding)
timeFrame: At Day 1 in ABCWY (0,6-months) and Control groups, Day 31 in ABCWY groups (0,2-months) and Day 211 in all study groups
measure: Number of Participants With 4-fold Rise in hSBA Titers Against Serogroup B Indicator Strains in Study Phase II (Formulation and Schedule-finding)
timeFrame: At Day 211 (1 month after the last vaccination)
measure: hSBA Geometric Mean Titers (GMTs) Against Serogroup B Indicator Strains in Study Phase II (Formulation and Schedule-finding)
timeFrame: At Day 1 in ABCWY groups (0,6-months) and Control groups, Day 31 in ABCWY groups (0,2-months) and Day 211 in all study groups
measure: hSBA Geometric Mean Ratios (GMRs) Against Serogroup B Indicator Strains in Study Phase II (Formulation and Schedule-finding)
timeFrame: At Day 211 in all study groups versus Day 1 in ABCWY (0,6-months) and Control groups and Day 31 in ABCWY groups (0,2-months)
measure: Number of Participants With hSBA Titers ≥ LLOQ for Serogroups A, C, W and Y in Study Phase II (Formulation and Schedule-finding)
timeFrame: Day 1 in ABCWY (0,6 Months) & Control; Day 31 pre-vaccination in ABCWY (0,2 Months); Day 31 post-first MenABCWY-2Gen in ABCWY (0,6 Months); Day 211 post-last MenABCWY-2Gen in all ABCWY; Day 31 post-MenACWY in Control
measure: Number of Participants With a 4-fold Rise in hSBA Titers Against Serogroups A, C, W and Y in Study Phase II (Formulation and Schedule-finding)
timeFrame: At Day 31 (1 month after the first MenABCWY-2Gen vaccination) in ABCWY (0,6-months) groups
measure: hSBA GMTs Against Serogroups A, C, W and Y in Study Phase II (Formulation and Schedule-finding)
timeFrame: Day 1 in ABCWY (0,6 Months) & Control; Day 31 pre-vaccination in ABCWY (0,2 Months); Day 31 post-first MenABCWY-2Gen in ABCWY (0,6 Months); Day 211 post-last MenABCWY-2Gen in all ABCWY; Day 31 post-MenACWY in Control
measure: hSBA GMRs Against Serogroups A, C, W and Y in Study Phase II (Formulation and Schedule-finding)
timeFrame: At Day 31 [for ABCWY (0,6-months) and Control group compared to Day 1 (Baseline)], at Day 211 [for ABCWY (0,6-months) groups compared to Day 1 (baseline) and for ABCWY (0,2-months) groups compared to Day 31]
measure: Immunoglobulin G (IgG) Antibodies Against Serogroups A, C, W and Y in Study Phase II (Formulation and Schedule-finding)
timeFrame: Day 1 in ABCWY (0,6 Months) & Control; Day 31 pre-vaccination in ABCWY (0,2 Months); Day 31 post-first MenABCWY-2Gen in ABCWY (0,6 Months); Day 211 post-last MenABCWY-2Gen in all ABCWY; Day 31 post-MenACWY in Control
Other outcomes:
Locations:
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Longmont
country: United States
facility: GSK Investigational Site
state: Colorado
city: Doral
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami Lakes
country: United States
facility: GSK Investigational Site
state: Florida
city: Meridian
country: United States
facility: GSK Investigational Site
state: Idaho
city: Nampa
country: United States
facility: GSK Investigational Site
state: Idaho
city: Springfield
country: United States
facility: GSK Investigational Site
state: Missouri
city: Lincoln
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Darlinghurst
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Fortitude Valley
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Taringa
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Tarragindi
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Nedlands
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Spearwood
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Brussels
country: Belgium
facility: GSK Investigational Site
city: Edegem
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Linkebeek
country: Belgium
facility: GSK Investigational Site
city: Rio de Janeiro
country: Brazil
facility: GSK Investigational Site
city: Salvador
country: Brazil
facility: GSK Investigational Site
city: Sao Jose Do Rio Preto
country: Brazil
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Elblag
country: Poland
facility: GSK Investigational Site
city: Katowice
country: Poland
facility: GSK Investigational Site
city: Katowice
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Lubon
country: Poland
facility: GSK Investigational Site
city: Siemianowice Slaskie
country: Poland
facility: GSK Investigational Site
city: Tarnow
country: Poland
facility: GSK Investigational Site
city: Torun
country: Poland
facility: GSK Investigational Site
city: Trzebnica
country: Poland
facility: GSK Investigational Site
city: Warsaw
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Boras
country: Sweden
facility: GSK Investigational Site
city: Karlskrona
country: Sweden
facility: GSK Investigational Site
city: Orebro
country: Sweden
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: Umea
country: Sweden
facility: GSK Investigational Site
city: Istanbul
country: Turkey
facility: GSK Investigational Site
city: Kocaeli
country: Turkey
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: