Clinical trial NCT06382311: A Study to Find and Confirm the Dose and Assess Safety, Reactogenicity and Immune Response of a Vaccine Against Pandemic H5N1 Influenza Virus in Healthy Younger and Older Adults
Official title: A PHASE 1/2, RANDOMIZED, PARTIALLY-BLIND, DOSE-FINDING/DOSE-CONFIRMATION STUDY TO EVALUATE THE SAFETY, REACTOGENICITY AND IMMUNOGENICITY OF THE MRNA-BASED INVESTIGATIONAL PANDEMIC H5 INFLUENZA VACCINE CANDIDATE ADMINISTERED IN HEALTHY YOUNGER AND OLDER ADULTS
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Influenza, Human
Keywords: Influenza A virus
Avian influenza
Flu pandemic
Healthy younger adults
Healthy older adults
Safety
Reactogenicity
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-04-24
Enrollment: 996
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: The aim of this study is to evaluate the safety, reactogenicity and immunogenicity of the Flu Pandemic messenger RNA (mRNA) vaccine (including dose-finding and dose-confirmation) administered in healthy adults 18 to 85 years of age.

Detailed description: Phase 1 (Ph1) of the study aims to evaluate the reactogenicity, safety, and immunogenicity of 5 dose levels of the investigational vaccine, compared with a placebo, in both younger adults (YA) and older adults (OA). Participants will receive two doses, 21 days apart, with safety data collected up to Day 29. The data from this phase will support the safety evaluation of the assessed dose levels and enable further assessment in higher number of participants in Phase 2 Part A.

Phase 2 (Ph2) Part A will assess the immunogenicity, reactogenicity, and safety of the same 5 dose levels evaluated in Phase 1, with the aim of identifying the doses to proceed to Phase 2 Part B.

Phase 2 Part B will descriptively characterize the dose level of the Flu Pandemic mRNA vaccine candidate selected from Phase 2 Part A, comparing it to an influenza vaccine in a 2-dose schedule. It will also assess safety, reactogenicity, and the immune response induced by the influenza vaccine.

Eligibility criteria: Inclusion Criteria:

* A male or female between and including 18 and 64 yoa (i.e., 64 years + 364 days; YAs) or between and including 65 and 85 yoa (i.e., 85 years + 364 days; OAs) at the time of the first study intervention administration.
* Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the eDiary, return for follow-up visits).
* Body mass index (BMI) more than or equal to (≥)18 kilogram per square meter (kg/m²) and less than or equal to (≤) 35kg/m².
* Written informed consent obtained from the participant prior to performance of any study-specific procedure.
* Healthy participants or medically stable patients as established by medical history, clinical examination, and screening safety laboratory assessments (Where applicable) Participants with chronic medical conditions with or without specific treatment (e.g., chronic metabolic, cardiac, pulmonary, renal, hepatic, neurologic, and hematologic diseases) are allowed to participate in this study, if considered by the investigator as medically stable. A stable medical condition is defined as disease not requiring change in therapy or hospitalization for worsening disease during 3 months before enrollment.
* Females of nonchildbearing potential may be enrolled in the study.
* Females 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 at Screening Visit (if applicable) and on the day of each study intervention administration, and
  * has agreed to continue adequate contraception for at least 1 month after completion of the last dose of study intervention.

Exclusion Criteria:

Medical conditions

* Where applicable, FDA toxicity grades will be exclusionary.
* Planned administration of an influenza vaccine before Day 43 time point.
* Current or past malignancy, unless completely resolved without clinically significant sequelae (e.g., no evidence of disease following successful treatment of basal cell carcinoma cases are allowed) for \>5 years.
* Has any medical disease or psychiatric condition that, in the opinion of the investigator, precludes study participation because it would place the participant at an unacceptable risk of injury, would render them unable to meet the requirements of the protocol, or may interfere with successful completion of the study.
* Has a bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following intramuscular (IM) injections.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection, based on medical history and physical examination (no laboratory testing required). However, in Phase 2, HIV-infected individuals may be enrolled if they have been stable on antiretroviral therapy for the past 6 consecutive months, i.e., their treatment has not been modified, their CD4 cell count is ≥200/mm³ and their viral load has been undetectable (i.e., HIV-RNA \<50 copies/mL) (based on medical records, no laboratory testing required).
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s) (including polyethylene glycol, aminoglycoside antibiotics and egg products).
* History of uncontrolled neurological disorders or seizures, including Guillain-Barré syndrome and Bell's palsy, with the exception of febrile seizures during childhood.
* Any history of dementia or any medical condition that moderately or severely impairs cognition.
* History of or current suspicion of myocarditis or pericarditis (including following administration, of an mRNA vaccine); or idiopathic cardiomyopathy, or presence of any medical condition that increases the risk myocarditis or pericarditis, including cocaine abuse, cardiomyopathy, endomyocardial fibrosis, hypereosinophilic syndrome, hypersensitivity myocarditis, eosinophilic granulomatosis with polyangiitis and persistent myocardial infection.
* 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 invasive medical device) other than the study intervention(s) during the period beginning 28 days before the dose of study intervention(s) (Day -28 to Day 1), or their planned use during the study period.
* Administration of a vaccine not foreseen by the study protocol in the period starting 28 days before the study intervention administration or planned administration within 21 days after the (last) study intervention administration\*.

  \*If emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) is recommended and/or organized by public health authorities outside the routine immunization program, the time period described above can be reduced to 7 days if, necessary for that vaccine, provided it is used according to the local governmental recommendations and that the Sponsor is notified accordingly.
* Chronic administration of immune-modifying drugs (defined as more than 14 consecutive days in total) and/or planned use of long-acting immune-modifying treatments at any time up to the end of the study.

  * Up to 3 months prior to the study intervention administration:
  * For corticosteroids, this will mean prednisone equivalent 20 mg/day. Inhaled, intra-articular and topical corticosteroids are allowed. If systemic corticosteroids have been administered short term (\<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 28 days before study vaccine administration.
  * Up to 3 months prior to study intervention administration: long-acting immune-modifying drugs including among others immunotherapy (e.g., TNF-inhibitors), monoclonal antibodies, antitumoral medication.
* Administration of immunoglobulins and/or any blood products or plasma derivatives within 3 months before study intervention administration through end of study.

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).
* Participated in an A(H5) influenza vaccine study in the past or have a history of A(H5) influenza infection prior to dosing in this study. This includes influenza subtypes A(H5N1), A(H5N8), A(H5N6).

Other exclusion criteria

* Pregnant or lactating female participant.
* Female planning to become pregnant or planning to discontinue contraceptive precautions within 1 months after completion of the vaccination series.
* Has a history of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures.
* Any study personnel or their immediate dependents, family, or household members.
* Participants with extensive tattoos covering deltoid region on both arms that would preclude the assessment of local reactogenicity.
* Planned move during the study period that will prohibit participating in the study until study end.
* Donation of blood 3 months prior to the study intervention administration and during the study period.

Primary outcomes:
measure: Percentage of participants with solicited administration site events [Phase 1 and Phase 2 Part A]
timeFrame: From Day 1 to Day 7
measure: Percentage of participants with solicited administration site events [Phase 1 and Phase 2 Part A]
timeFrame: From Day 22 to Day 28
measure: Percentage of participants with solicited systemic events [Phase 1 and Phase 2 Part A]
timeFrame: From Day 1 to Day 7
measure: Percentage of participants with solicited systemic events [Phase 1 and Phase 2 Part A]
timeFrame: From Day 22 to Day 28
measure: Percentage of participants with unsolicited adverse events (AEs) [Phase 1 and Phase 2 Part A]
timeFrame: From Day 1 to Day 21
measure: Percentage of participants with unsolicited adverse events (AEs) [Phase 1 and Phase 2 Part A]
timeFrame: From Day 22 to Day 42
measure: Percentage of participants with medically attended adverse events (MAAEs) [Phase 1 and Phase 2 Part A]
timeFrame: From Day 1 to Day 203
measure: Percentage of participants with serious adverse events (SAEs) [Phase 1 and Phase 2 Part A]
timeFrame: From Day 1 to Day 203
measure: Percentage of participants with adverse events of special interest (AESIs) [Phase 1 and Phase 2 Part A]
timeFrame: From Day 1 to Day 203
measure: Phase 1: Percentage of participants with increase in FDA toxicity grading for hematology and clinical chemistry laboratory parameters from baseline to any level of FDA toxicity grading at Day 8
timeFrame: Baseline (Day 1), Day 8
measure: Phase 1: Percentage of participants with increase in FDA toxicity grading in hematology and clinical chemistry laboratory parameters from baseline to any level of FDA toxicity grading at Day 29
timeFrame: Baseline (Day 1), Day 29
measure: Phase 1: Percentage of participants with increase in haematology and clinical chemistry laboratory parameters from normal values at baseline to abnormal values at Day 8
timeFrame: Baseline (Day 1), Day 8
measure: Phase 1: Percentage of participants with increase in hematology and clinical chemistry laboratory parameters from normal values at baseline to abnormal values at Day 29
timeFrame: Baseline (Day 1), Day 29
measure: Percentage of participants with anti- hemagglutinin inhibition (HI) titers ≥ 1:40 at Day 43 [Phase 1 and Phase 2 Part A]
timeFrame: At Day 43
measure: Percentage of participants with solicited administration site events [Phase 2 Part B]
timeFrame: From Day 1 to Day 7
measure: Percentage of participants with solicited administration site events [Phase 2 Part B]
timeFrame: From Day 22 to Day 28
measure: Percentage of participants with solicited systemic events [Phase 2 Part B]
timeFrame: From Day 1 to Day 7
measure: Percentage of participants with solicited systemic events [Phase 2 Part B]
timeFrame: From Day 22 to Day 28
measure: Percentage of participants with unsolicited AEs [Phase 2 Part B]
timeFrame: From Day 1 to Day 21
measure: Percentage of participants with unsolicited AEs [Phase 2 Part B]
timeFrame: From Day 22 to Day 42
measure: Percentage of participants with MAAEs [Phase 2 Part B]
timeFrame: From Day 1 to Day 203
measure: Percentage of participants with SAEs [Phase 2 Part B]
timeFrame: From Day 1 to Day 203
measure: Percentage of participants with AESIs [Phase 2 Part B]
timeFrame: From Day 1 to Day 203
measure: Percentage of participants with increase in FDA toxicity grading for clinical chemistry laboratory parameters from baseline to any level of FDA toxicity grading at Day 8 [Phase 2 Part B]
timeFrame: Baseline (Day 1), Day 8
measure: Percentage of participants with increase in FDA toxicity grading for clinical chemistry laboratory parameters from baseline to any level of FDA toxicity grading at Day 29 [Phase 2 Part B]
timeFrame: Baseline (Day 1), Day 29
measure: Percentage of participants with increase in clinical chemistry laboratory parameters from normal values at baseline to abnormal values at Day 8 [Phase 2 Part B]
timeFrame: Baseline (Day 1), Day 8
measure: Percentagev of participants with increase in clinical chemistry laboratory parameters from normal values at baseline to abnormal values at Day 29 [Phase 2 Part B]
timeFrame: Baseline (Day 1), Day 29
measure: Percentage of participants with anti-HI titers ≥ 1:40 at Day 43 [Phase 2 Part B]
timeFrame: At Day 43
measure: Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B]
timeFrame: At Day 43 compared to pre-vaccination (Day 1, pre-dosing)
measure: GMT Ratio of anti-HI antibody titers [Phase 2 Part B]
timeFrame: At Day 43
Secondary outcomes:
measure: Geometric mean titers (GMTs) of HI antibody titers [Phase 1 and Phase 2 Part A]
timeFrame: At Day 1, Day 22, Day 29, Day 43, and Day 203
measure: Geometric mean increase (GMI) of HI antibody titers [Phase 1 and Phase 2 Part A]
timeFrame: At Day 22 compared to pre-vaccination (Day 1, pre-dosing)
measure: Geometric mean increase (GMI) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]
timeFrame: At Day 29 compared to pre-vaccination (Day 1, pre-dosing)
measure: Geometric mean increase (GMI) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]
timeFrame: At Day 43 compared to pre-vaccination (Day 1, pre-dosing)
measure: Geometric mean increase (GMI) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]
timeFrame: At Day 203 compared to pre-vaccination (Day 1, pre-dosing)
measure: Percentage of participants with HI antibody Seroconversion rate (SCR) [Phase 1 and Phase 2 Part A]
timeFrame: At Day 22 compared to pre-vaccination (Day 1, pre-dosing)
measure: Seroconversion rate (SCR) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]
timeFrame: At Day 29 compared to pre-vaccination (Day 1, pre-dosing)
measure: Seroconversion rate (SCR) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]
timeFrame: At Day 43 compared to pre-vaccination (Day 1, pre-dosing)
measure: Seroconversion rate (SCR) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]
timeFrame: At Day 203 compared to pre-vaccination (Day 1, pre-dosing)
measure: Percentage of participants with anti-HI antibody titers >= 1:40 [Phase 1 and Phase 2 Part A]
timeFrame: At Day 22, Day 29, and Day 203
measure: Percentage of seropositive participants for the HA antibody titers [Phase 1 and Phase 2 Part A]
timeFrame: At Day 1, Day 22, Day 29, Day 43, and Day 203
measure: GMT of Anti-HI antibody titers [Phase 2 Part B]
timeFrame: At Day 1, Day 22, Day29, Day 43 and Day 203
measure: GMI of anti-HI antibody titers [Phase 2 Part B]
timeFrame: At Day 22 compared to pre-vaccination (Day 1, pre-dosing)
measure: GMI of anti-HI antibody titers [Phase 2 Part B]
timeFrame: At Day 29 compared to pre-vaccination (Day 1, pre-dosing)
measure: GMI of anti-HI antibody titers [Phase 2 Part B]
timeFrame: At Day 43 compared to pre-vaccination (Day 1, pre-dosing)
measure: GMI of anti-HI antibody titers [Phase 2 Part B]
timeFrame: At Day 203 compared to pre-vaccination (Day 1, pre-dosing)
measure: Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B]
timeFrame: At Day 22 compared to pre-vaccination (Day 1, pre-dosing)
measure: Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B]
timeFrame: At Day 29 compared to pre-vaccination (Day 1, pre-dosing)
measure: Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B]
timeFrame: At Day 43 compared to pre-vaccination (Day 1, pre-dosing)
measure: Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B]
timeFrame: At Day 203 compared to pre-vaccination (Day 1, pre-dosing)
measure: Percentage of participants with anti-HI antibody >= 1:40 [Phase 2 Part B]
timeFrame: At Day 1, Day 22, Day 29, Day 43 and Day 203
measure: Percentage of participants with seropositivity of anti-HI antibody titers [Phase 2 Part B]
timeFrame: At Day 1, Day 22, Day 29, Day 43 and Day 203
Other outcomes:
Locations:
city: Anniston
country: United States
facility: GSK Investigational Site
state: Alabama
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Fort Collins
country: United States
facility: GSK Investigational Site
state: Colorado
city: Fort Myers
country: United States
facility: GSK Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Chamblee
country: United States
facility: GSK Investigational Site
state: Georgia
city: El Dorado
country: United States
facility: GSK Investigational Site
state: Kansas
city: Lenexa
country: United States
facility: GSK Investigational Site
state: Kansas
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Greensboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Edmond
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Yukon
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Norfolk
country: United States
facility: GSK Investigational Site
state: Virginia
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
References: