A Study to Assess the Safety and Immune Response of a Vaccine Against Influenza in Healthy Younger and Older Adults

Phase 1

Completed

Conditions: Influenza, Human

Interventions: Biological: F2C22C/DL001Z
Biological: F2B22A/DL001Z
Biological: F2B22B/DL001Z
Biological: F2B22C/DL001Z
Biological: F2B22D/DL001Z
Biological: F2B22E/DL001Z
Biological: F2F22A/DL001Z
Biological: F2F22B/DL001Z
Biological: F2F22C/DL001Z
Biological: F2F22D/DL001Z
Biological: F2F22E/DL001Z
Biological: F2F22F/DL001Z
Combination Product: Control 1
Biological: F2F23D/DL001Z-NH
Biological: F2F23A/DL001Z-NH
Biological: F2F23B/DL001Z-NH
Combination Product: Control 2
Biological: F2F23C/DL001Z-NH
Combination Product: Control 3

Registration Number: NCT05823974

Lead Sponsor: GlaxoSmithKline

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1275

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Flu mRNA_Ph1_1 Younger Adults (YA) Group	F2C22C/DL001Z	YA Participants received a single dose of Flu mRNA study intervention F2C22C/DL001Z (GSKVx000000039714) administered in Phase 1, at Day 1.
Flu mRNA_Ph1_2 YA Group	F2B22A/DL001Z	YA participants received a single dose of Flu mRNA study intervention F2B22A/DL001Z (GSKVx000000040038) administered in Phase 1, at Day 1.
Flu mRNA_Ph1_3 YA Group	F2B22B/DL001Z	YA participants received a single dose of Flu mRNA study intervention F2B22B/DL001Z (GSKVx000000040668) administered in Phase 1, at Day 1.
Flu mRNA_Ph1_4 YA Group	F2B22C/DL001Z	YA participants received a single dose of Flu mRNA study intervention F2B22C/DL001Z (GSKVx000000040671) administered in Phase 1, at Day 1.
Flu mRNA_Ph1_5 YA Group	F2B22D/DL001Z	YA participants received a single dose of Flu mRNA study intervention F2B22D/DL001Z (GSKVx000000040674) administered in Phase 1, at Day 1.
Flu mRNA_Ph1_6 YA Group	F2B22E/DL001Z	YA participants received a single dose of Flu mRNA study intervention F2B22E/DL001Z (GSKVx000000040677) administered in Phase 1, at Day 1.
Flu mRNA_Ph1_7 YA Group	F2F22A/DL001Z	YA participants received a single dose of Flu mRNA study intervention F2F22A/DL001Z (GSKVx000000040641) administered in Phase 1, at Day 1.
Flu mRNA_Ph1_8 YA Group	F2F22B/DL001Z	YA participants received a single dose of Flu mRNA study intervention F2F22B/DL001Z (GSKVx000000040644) administered in Phase 1, at Day 1.
Flu mRNA_Ph1_9 YA Group	F2F22C/DL001Z	YA participants received a single dose of Flu mRNA (GSK4382276A) study intervention F2F22C/DL001Z (GSKVx000000040647) administered in Phase 1, at Day 1.
Flu mRNA_Ph1_10 YA Group	F2F22D/DL001Z	YA participants received a single dose of Flu mRNA study intervention F2F22D/DL001Z (GSKVx000000040650) administered in Phase 1, at Day 1.
Flu mRNA_Ph1_11 YA Group	F2F22E/DL001Z	YA participants received a single dose of Flu mRNA study intervention F2F22E/DL001Z (GSKVx000000040996) administered in Phase 1, at Day 1.
Flu mRNA_Ph1_12 YA Group	F2F22F/DL001Z	YA participants received a single dose of Flu mRNA study intervention F2F22F/DL001Z (GSKVx000000040999) administered in Phase 1, at Day 1.
Control Ph1_YA Group	Control 1	YA participants received a single dose of Control 1 administered in Phase 1, at Day 1.
Flu mRNA_Ph2_1_YA Group	F2F23D/DL001Z-NH	YA participants received a single dose of Flu mRNA study intervention F2F23D/DL001Z-NH administered in Phase 2, at Day 1.
Flu mRNA_Ph2_2_YA Group	F2F23A/DL001Z-NH	YA participants received a single dose of Flu mRNA study intervention F2F23A/DL001Z-NH administered in Phase 2, at Day 1.
Flu mRNA_Ph2_3_YA Group	F2F23B/DL001Z-NH	YA participants received a single dose of Flu mRNA study intervention F2F23B/DL001Z-NH administered in Phase 2, at Day 1.
Control_Ph2_YA Group	Control 2	YA participants received single dose of Control 2 vaccine administered in Phase 2, at Day 1.
Flu mRNA_Ph2_1_Older adults (OA) Group	F2F23A/DL001Z-NH	OA participants received a single dose of Flu mRNA study intervention F2F23A/DL001Z-NH administered in Phase 2, at Day 1.
Flu mRNA_Ph2_2_OA Group	F2F23B/DL001Z-NH	OA participants received a single dose of Flu mRNA study intervention F2F23B/DL001Z-NH administered in Phase 2, at Day 1.
Flu mRNA_Ph2_3_OA Group	F2F23C/DL001Z-NH	OA participants received a single dose of Flu mRNA study intervention F2F23C/DL001Z-NH administered in Phase 2, at Day 1.
Control_Ph2_OA Group	Control 3	OA participants received a single dose of Control 3 vaccine administered in Phase 2, at Day 1.

Primary Outcome Measures

Name	Time	Method
Number of Participants Reporting Any Solicited Administration Site Adverse Events (AEs)	Day 1 to Day 7	Assessed solicited administration site events included pain, redness (Erythema), swelling, lymphadenopathy (defined as localized axillary, cervical or supraclavicular swelling or tenderness ipsilateral to the injection arm). Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.
Number of Participants Reporting Any Solicited Systemic AEs	Day 1 to Day 7	Assessed solicited systemic events included fever (defined as axillary temperature greater than or equal to (\>=) 38.0°C/100.4°F), chills, headache, fatigue, myalgia, and arthralgia. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.
Number of Participants Reporting Any Unsolicited AEs	Day 1 to Day 28	An unsolicited AE is defined as an AE that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow up for solicited events. Unsolicited AEs include both serious and non-serious AEs. Any = occurrence the event regardless of intensity grade or relation to the study vaccination.
Number of Participants Reporting Serious Adverse Events (SAEs)	Day 1 to Day 183	An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, is an abnormal pregnancy outcome, or is a suspected transmission of any infectious agent via an authorized medicinal product. Any = occurrence the event regardless of intensity grade or relation to the study vaccination.
Number of Participants Reporting AEs of Special Interest (AESIs)	Day 1 to Day 183	The following events were considered as AESI in this study: severe hypersensitivity reactions within 24 hours after study intervention administration, myocarditis/pericarditis and potential immune-mediated diseases (pIMDs). Any = occurrence the event regardless of intensity grade or relation to the study vaccination.
Number of Participants Reporting Medically Attended Events (MAEs)	Day 1 to Day 183	MAE is defined as an AE that results in an unscheduled visit to a medical professional (e.g., physician's office visits, emergency room visits or hospitalization). Any = occurrence the event regardless of intensity grade or relation to the study vaccination.
Number of Participants Reporting a Shift From Abnormal Non-clinically Significant and Normal or Missing Laboratory Value on Day 1 to Clinically Significant Abnormal Laboratory Value on Day 8 for Hematology, and Clinical Chemistry	At Day 8 compared to baseline (Day 1)	Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participants condition. Normal or missing values refer to laboratory values that were within normal range or missing at baseline.
Number of Participants Reporting a Shift From Abnormal Non-clinically Significant and Normal or Missing Laboratory Value on Day 1 to Clinically Significant Abnormal Laboratory Value on Day 29 for Hematology, and Clinical Chemistry	At Day 29 compared to baseline (Day 1)	Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participants condition. Normal or missing values refer to laboratory values that were within normal range or missing at baseline.
Geometric Mean Titer (GMT) of Antigen 1 Antibody Titer	At Day 29	Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Geometric Mean Increase (GMI) of Antigen 1 Antibody Titers From Day 1 to Day 29	From Day 1 (baseline) to Day 29	GMI is defined as the geometric mean of the ratios of the post dosing titer over the Day 1 titer. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Percentage of Participants With Antigen 1 Antibody Seroconversion Rate (SCR)	From Day 1 to Day 29	SCR is defined as the percentage of dosed participants who have either an anti-vaccine antibody pre-dose titer \< 1:10 and a post-dose anti-vaccine antibody titer \>= 1:40 or a pre-dose anti-vaccine antibody titer \>= 1:10 and at least a 4-fold increase in post-dose anti-vaccine antibody titer. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Percentage of Participants With Antigen 1 Antibody Seroprotection Rate (SPR)	At Day 1	SPR is defined as the percentage of dosed participants with a anti-vaccine antibody titer \>= 1:40. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Percentage of Participants With Antigen 1 Antibody SPR	At Day 29	Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
GMT of Antigen 2 Antibody Titer	At Day 29
GMI of Antigen 2 Antibody Titer From Day 1 to Day 29	From Day 1 (baseline) to Day 29
Percentage of Participants With Antigen 2 Antibody SCR	From Day 1 to Day 29

Secondary Outcome Measures

Name	Time	Method
GMT of Antigen 1 Antibody Titer	At Day 183	Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
GMI of Antigen 1 Antibody Titer From Day 1 to Day 92	From Day 1 (baseline) to Day 92	Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
GMI of Antigen 1 Antibody Titer From Day 1 to Day 183	From Day 1 (baseline) to Day 183	Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Percentage of Participants With Antigen 1 Antibody SPR	At Day 183	Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
GMT of Antigen 2 Antibody Titer	At Day 92 and Day 183
GMI of Antigen 2 Antibody Titer	From Day 1 to Day 92 and Day 1 to Day 183