Clinical trial NCT06431607: A Study to Find the Dose and Assess the Immune Response and Safety of a Vaccine Against Influenza in Healthy Younger and Older Adults
Official title: A Phase 2a Randomized, Observer-blind, Dose-finding Study to Evaluate the Immunogenicity and Safety of mRNA-based Multivalent Seasonal Influenza Vaccine Candidates in Adults 18 Years of Age and Older
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Influenza, Human
Keywords: Influenza
Safety
Reactogenicity
Immunogenicity
mRNA vaccine
Healthy younger adults
Healthy older adults
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-05-28
Enrollment: 843
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the safety and immune response of GlaxoSmithKlines (GSK) messenger RNA (mRNA)-based multivalent vaccine (GSK4382276A) candidate against influenza, administered in healthy younger adults (YA) and older adults (OA).


Eligibility criteria: Inclusion Criteria:

1. A male or female between and including 18 and 85 years of age (YAs: 18-64; OAs: 65-85) at the time of the study intervention administration.
2. Healthy participants or medically stable patients as established by medical history and clinical examination. 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 significant change in therapy or hospitalization for worsening disease during 3 months before enrolment.
3. Body mass index (BMI) \>=18 Kilograms per meter square (kg/m²) and less than or equal to (\<=) 35kg/m2.
4. Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits), independently or with the assistance of a caregiver.
5. Written informed consent obtained from the participant prior to performance of any study-specific procedure.
6. Female participants of non-childbearing potential may be enrolled in the clinical study.
7. Female participants of childbearing potential may be enrolled in the clinical study, if the participant:

   * Has practiced adequate contraception for 1 month prior to the study intervention administration, and
   * Has a negative pregnancy test within 24 hours prior to the study intervention administration, and
   * Has agreed to continue adequate contraception for at least 1 month after study intervention administration.

Exclusion Criteria:

1. Participant tested positive for influenza by local health authority-approved testing methods within 180 days prior to Day 1.
2. Current or past malignancy, unless completely resolved without sequelae for greater than (\>) 5 years before the study intervention administration (excluding effectively treated basal cell skin cancer).
3. Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination (no laboratory testing required). 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 cluster of differentiation 4 (CD4) cell count is \>= 200/ cubic millimeter (mm³) and their viral load has been undetectable (i.e., HIV-RNA lesser than (\<) 50 copies/milliliter \[mL\]) (based on medical records, no laboratory testing required).
4. Participants with a history of, or current suspicion of myocarditis, pericarditis, or idiopathic cardiomyopathy (including a history of myocarditis or pericarditis following vaccination with an mRNA COVID-19 vaccine), or presence of any medical condition that increases risk of myocarditis or pericarditis, including cocaine abuse, cardiomyopathy, endomyocardial fibrosis, hypereosinophilic syndrome, hypersensitivity myocarditis, eosinophilic granulomatosis with polyangiitis and persistent myocardial infection will be excluded from the study.
5. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention (including polyethylene glycol, egg proteins and aminoglycoside antibiotics).
6. Hypersensitivity to latex.
7. Recurrent history or uncontrolled neurological disorders or seizures, including Guillain-Barré syndrome and Bell's palsy, with the exception of febrile seizures during childhood.
8. Any history of dementia or any medical condition that moderately or severely impairs cognition.
9. Any condition that in the judgment of the investigator would make intramuscular injection unsafe.
10. Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the clinical study.
11. Administration of an influenza vaccine within 180 days before enrollment or planned administration prior to Visit 2 (Day 29) after the study intervention administration.
12. Previous vaccination with a mRNA influenza vaccine.
13. Administration of a vaccine not foreseen by the study protocol in the period starting 30 days (Day -30) before the study intervention administration, or planned administration within 28 days (Visit 2 \[Day 29\]) after the 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, provided it is used according to the local governmental recommendations and sponsor is notified.
14. Use of any investigational or non-registered product (drug, vaccine or invasive medical device) other than the study intervention during the period beginning 30 days before the study intervention administration, or their planned use during the study period.
15. Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the study intervention administration or planned administration during the study period.
16. 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, intraarticular and topical steroids are allowed.
    * 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.
17. 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).
18. Pregnant or lactating female participant.
19. Bedridden participants.
20. Female participant planning to become pregnant or planning to discontinue contraceptive precautions within the 1-month post-dosing period.
21. History of chronic alcohol consumption and/or drug abuse in the past 5 years as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures.
22. Any study personnel or their immediate dependents, family, or household members.
23. Participants with extensive tattoos covering deltoid region on both arms that would preclude the assessment of local reactogenicity.

Primary outcomes:
measure: Geometric mean titer (GMT) of antigen 1 antibody
timeFrame: At Day 29
measure: Geometric mean increase (GMI) of Antigen 1 antibody titer
timeFrame: From Day 1 to Day 29
measure: Percentage of participants with antigen 1 seroconversion rate (SCR)
timeFrame: From Day 1 to Day 29
measure: Percentage of participants with antigen 1 titer greater than or equal to (>=) the cut off value at Day 1
timeFrame: At Day 1
measure: Percentage of participants with antigen 1 titer >= the cut off value at Day 29
timeFrame: At Day 29
Secondary outcomes:
measure: GMT of antigen 2 antibody
timeFrame: At Day 29
measure: GMI of antigen 2 antibody titer
timeFrame: From Day 1 to Day 29
measure: Percentage of participants with Antigen 2 SCR
timeFrame: From Day 1 to Day 29
measure: Percentage of participants reporting each solicited administration site event
timeFrame: Day 1 to Day 7
measure: Percentage of participants reporting each solicited systemic event
timeFrame: Day 1 to Day 7
measure: Percentage of participants reporting unsolicited adverse events (AEs)
timeFrame: Day 1 to Day 28
measure: Percentage of participants reporting serious adverse events (SAEs)
timeFrame: Day 1 to Day 183
measure: Percentage of participants reporting adverse events of special interest (AESIs)
timeFrame: Day 1 to Day 183
measure: Percentage of participants reporting medically attended adverse events (MAAEs)
timeFrame: Day 1 to Day 183
Other outcomes:
Locations:
city: Hialeah
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Valparaiso
country: United States
facility: GSK Investigational Site
state: Indiana
city: El Dorado
country: United States
facility: GSK Investigational Site
state: Kansas
city: Lenexa
country: United States
facility: GSK Investigational Site
state: Kansas
city: Newton
country: United States
facility: GSK Investigational Site
state: Kansas
city: Wichita
country: United States
facility: GSK Investigational Site
state: Kansas
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
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: Knoxville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Tomball
country: United States
facility: GSK Investigational Site
state: Texas
city: Newport News
country: United States
facility: GSK Investigational Site
state: Virginia
city: Norfolk
country: United States
facility: GSK Investigational Site
state: Virginia
Study officials:
References: