Clinical trial NCT05823974: A Study to Assess the Safety and Immune Response of a Vaccine Against Influenza in Healthy Younger and Older Adults
Official title: A Phase 1/2, Randomized, Dose-finding/Dose-confirmation Study to Evaluate the Reactogenicity, Safety and Immunogenicity of mRNA-based Multivalent Seasonal Influenza Vaccine Candidates Administered in Healthy Younger and Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Influenza, Human
Keywords: Influenza
Safety
Reactogenicity
Immunogenicity
mRNA vaccine
Healthy younger adults
Healthy older adults
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: CureVac
First posted: 2023-04-21
Enrollment: 1268
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 find and confirm the dose and asses the reactogenicity, safety and immune response of GlaxoSmithKline's (GSK) messenger RNA (mRNA)-based multivalent seasonal influenza vaccine (GSK4382276A) candidates administered in healthy younger and older adults (OA).


Eligibility criteria: Inclusion Criteria:

* A male or female between and including 18 and 50 years of age in Phase 1 and between and including 18 and 85 years of age (YA: 18-64; OA: 65-85) in Phase 2 at the time of the study intervention administration.
* Healthy participants or medically stable participants as established by medical history, clinical examination, and safety laboratory assessments. Participants with chronic medical conditions with or without specific treatment 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 enrollment.
* Body mass index (BMI) \>=18 kilograms per meter square (kg/m\^2) and less than or equal to (\<=) 35 kg/m\^2.
* Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* Written informed consent obtained from the participant prior to performing any study-specific procedure.
* Female participants of non-childbearing potential may be enrolled in the study.
* Female participants of childbearing potential may be enrolled in the study if the participant:
* has practiced adequate contraception for 28 days 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 for at least 1 month after study intervention administration

Exclusion Criteria:

Medical conditions

* Only in Phase 1: Any clinically significant\* hematological, biochemical, urinalysis or (hemoglobin A1c) HbA1c laboratory abnormality.

  \*The investigator should use the clinical judgment to decide which abnormalities are clinically significant.
* Participant tested positive for influenza by local health authority-approved testing methods within 180 days prior to Day 1.
* Current or past malignancy, unless completely resolved without clinically significant sequelae for \>5 years.
* 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 participants 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 (mm\^3) and their viral load has been undetectable (i.e., HIV-RNA less than (\<) 50 copies/milliliter \[mL\]) (based on medical records, no laboratory testing required).
* History of myocarditis or pericarditis less than or equal to 10 years prior to vaccine administration, including a history of myocarditis or pericarditis following vaccination with an mRNA coronavirus disease 2019 (COVID-19) vaccine.
* Participants with history of hypersensitivity or severe allergic reaction to any previous vaccine or hypersensitivity likely to be exacerbated by any component of the study intervention (including latex, polyethylene glycol, egg protein and aminoglycoside antibiotics).
* History of, or 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.
* Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
* 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

* Administration of an influenza vaccine (including any of the study investigational vaccines) within 180 days before enrollment or planned administration within 28 days (Day 29) after the study intervention administration.
* Phase 1: Administration of a vaccine not foreseen by the study protocol in the period starting 28 days (Day -28) before the study intervention administration or planned administration within 28 days (Day 29) after the study intervention administration. Phase 2: Administration of a vaccine not foreseen by the study protocol in the period starting 15 days (Day -15) before the study intervention administration or planned administration within 28 days (Day 29) after the study intervention administration.

  \*In case emergency mass vaccination for an unforeseen public health threat 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.
* 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.
* Administration of long-acting immune-modifying drugs within 90 days before enrollment or planned use at any time during the study period.
* 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. Administration of monoclonal antibodies specifically directed against the spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), for treatment of COVID-19 disease is allowed.
* 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 study intervention administration. For corticosteroids, this will mean prednisone equivalent \>=20 milligrams (mg)/day. Inhaled, topical and intraarticular steroids are allowed.

Other exclusions

* 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).
* Pregnant or lactating female.
* Bedridden participants.
* Female planning to become pregnant or planning to discontinue contraceptive precautions within the 1-month post-dosing period.
* Alcoholism or substance use disorder within the past 24 months based on the presence of 2 or more of the following abuse criteria: hazardous use, social/interpersonal problems related to use, neglect of major roles to use, withdrawal, tolerance, use of larger amounts or longer, repeated attempts to quit or control use, much time spent using, physical or psychological problems related to use, activities given up to use, craving.
* 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.

Primary outcomes:
measure: Percentage of participants reporting each solicited administration site event
timeFrame: From Day 1 to Day 7
measure: Percentage of participants reporting each solicited systemic event
timeFrame: From Day 1 to Day 7
measure: Percentage of participants reporting unsolicited adverse events (AEs)
timeFrame: From Day 1 to Day 28
measure: Percentage of participants reporting serious adverse events (SAEs)
timeFrame: From Day 1 to Day 183
measure: Percentage of participants reporting adverse events of special interest (AESIs)
timeFrame: From Day 1 to Day 183
measure: Percentage of participants reporting medically attended events (MAEs)
timeFrame: From Day 1 to Day 183
measure: Percentage of participants reporting a shift from a non-clinically significant laboratory value on Day 1 (pre-dose) to a clinically significant abnormal laboratory value on Day 8 (post-dose) and/or Day 29 (post-dose) for hematology and clinical chemistry
timeFrame: From Day 1 (pre-dose) to Day 8 (post-dose) and/or Day 29 (post-dose)
measure: Geometric mean titer (GMT) of antigen 1 antibody titer
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 >= cut off value
timeFrame: At Day 1 and Day 29
measure: GMT of antigen 2 antibody titer
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
Secondary outcomes:
measure: GMT of antigen 1 antibody titer
timeFrame: At Day 92 and Day 183
measure: GMI of antigen 1 antibody titer
timeFrame: From Day 1 to Day 92
measure: GMI of antigen 1 antibody titer
timeFrame: From Day 1 to Day 183
measure: Percentage of participants with antigen 1 titer >= cut off value
timeFrame: At Day 183
measure: GMT of antigen 2 antibody titer
timeFrame: At Day 92 and Day 183
measure: GMI of antigen 2 antibody titer
timeFrame: From Day 1 to Day 92
measure: GMI of antigen 2 antibody titer
timeFrame: From 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: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Valparaiso
country: United States
facility: GSK Investigational Site
state: Indiana
city: Lenexa
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: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Dearborn
country: United States
facility: GSK Investigational Site
state: Michigan
city: Papillion
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Denver
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Greensboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Dayton
country: United States
facility: GSK Investigational Site
state: Ohio
city: East Greenwich
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Knoxville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
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
city: Antwerpen
country: Belgium
facility: GSK Investigational Site
city: Edegem
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Ieper
country: Belgium
facility: GSK Investigational Site
city: Kluisbergen
country: Belgium
facility: GSK Investigational Site
city: Mechelen
country: Belgium
facility: GSK Investigational Site
city: Tielt
country: Belgium
facility: GSK Investigational Site
city: Zwalm
country: Belgium
facility: GSK Investigational Site
city: Halifax
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Truro
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Chicoutimi
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec
country: Canada
facility: GSK Investigational Site
city: Buffalo
country: South Africa
facility: GSK Investigational Site
city: Cape Town
country: South Africa
facility: GSK Investigational Site
city: Johannesburg
country: South Africa
facility: GSK Investigational Site
city: Tembisa
country: South Africa
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: