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

NCT05823974 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2178842022-502308-66-00
• Study Type: interventional
• Target: 1,275
• Locations: 4 countries
• Sites: 41

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).

Conditions

Influenza, Human

Keywords

Influenza; Safety; Reactogenicity; Immunogenicity; mRNA vaccine; Healthy younger adults; Healthy older adults

Outcome Measures

Primary Outcomes (16)

• Number of Participants Reporting Any Solicited Administration Site Adverse Events (AEs)

  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.

  Day 1 to Day 7

• Number of Participants Reporting Any Solicited Systemic AEs

  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.

  Day 1 to Day 7

• Number of Participants Reporting Any Unsolicited AEs

  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.

  Day 1 to Day 28

• Number of Participants Reporting Serious Adverse Events (SAEs)

  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.

  Day 1 to Day 183

• Number of Participants Reporting AEs of Special Interest (AESIs)

  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.

  Day 1 to Day 183

• Number of Participants Reporting Medically Attended Events (MAEs)

  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.

  Day 1 to Day 183

• 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

  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.

  At Day 8 compared to baseline (Day 1)

• 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

  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.

  At Day 29 compared to baseline (Day 1)

• Geometric Mean Titer (GMT) of Antigen 1 Antibody Titer

  Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.

  At Day 29

• Geometric Mean Increase (GMI) of Antigen 1 Antibody Titers From Day 1 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.

  From Day 1 (baseline) to Day 29

• Percentage of Participants With Antigen 1 Antibody Seroconversion Rate (SCR)

  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.

  From Day 1 to Day 29

• Percentage of Participants With Antigen 1 Antibody Seroprotection Rate (SPR)

  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.

  At Day 1

• Percentage of Participants With Antigen 1 Antibody SPR

  Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.

  At Day 29

• 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 Outcomes (7)

• GMT of Antigen 1 Antibody Titer

  At Day 92

• GMT of Antigen 1 Antibody Titer

  At Day 183

• GMI of Antigen 1 Antibody Titer From Day 1 to Day 92

  From Day 1 (baseline) to Day 92

• GMI of Antigen 1 Antibody Titer From Day 1 to Day 183

  From Day 1 (baseline) to Day 183

• Percentage of Participants With Antigen 1 Antibody SPR

  At Day 183

Study Arms (21)

Flu mRNA_Ph1_1 Younger Adults (YA) Group

EXPERIMENTAL

YA Participants received a single dose of Flu mRNA study intervention F2C22C/DL001Z (GSKVx000000039714) administered in Phase 1, at Day 1.

Biological: F2C22C/DL001Z

Flu mRNA_Ph1_2 YA Group

EXPERIMENTAL

YA participants received a single dose of Flu mRNA study intervention F2B22A/DL001Z (GSKVx000000040038) administered in Phase 1, at Day 1.

Biological: F2B22A/DL001Z

Flu mRNA_Ph1_3 YA Group

EXPERIMENTAL

YA participants received a single dose of Flu mRNA study intervention F2B22B/DL001Z (GSKVx000000040668) administered in Phase 1, at Day 1.

Biological: F2B22B/DL001Z

Flu mRNA_Ph1_4 YA Group

EXPERIMENTAL

YA participants received a single dose of Flu mRNA study intervention F2B22C/DL001Z (GSKVx000000040671) administered in Phase 1, at Day 1.

Biological: F2B22C/DL001Z

Flu mRNA_Ph1_5 YA Group

EXPERIMENTAL

YA participants received a single dose of Flu mRNA study intervention F2B22D/DL001Z (GSKVx000000040674) administered in Phase 1, at Day 1.

Biological: F2B22D/DL001Z

Flu mRNA_Ph1_6 YA Group

EXPERIMENTAL

YA participants received a single dose of Flu mRNA study intervention F2B22E/DL001Z (GSKVx000000040677) administered in Phase 1, at Day 1.

Biological: F2B22E/DL001Z

Flu mRNA_Ph1_7 YA Group

EXPERIMENTAL

YA participants received a single dose of Flu mRNA study intervention F2F22A/DL001Z (GSKVx000000040641) administered in Phase 1, at Day 1.

Biological: F2F22A/DL001Z

Flu mRNA_Ph1_8 YA Group

EXPERIMENTAL

YA participants received a single dose of Flu mRNA study intervention F2F22B/DL001Z (GSKVx000000040644) administered in Phase 1, at Day 1.

Biological: F2F22B/DL001Z

Flu mRNA_Ph1_9 YA Group

EXPERIMENTAL

YA participants received a single dose of Flu mRNA (GSK4382276A) study intervention F2F22C/DL001Z (GSKVx000000040647) administered in Phase 1, at Day 1.

Biological: F2F22C/DL001Z

Flu mRNA_Ph1_10 YA Group

EXPERIMENTAL

YA participants received a single dose of Flu mRNA study intervention F2F22D/DL001Z (GSKVx000000040650) administered in Phase 1, at Day 1.

Biological: F2F22D/DL001Z

Flu mRNA_Ph1_11 YA Group

EXPERIMENTAL

YA participants received a single dose of Flu mRNA study intervention F2F22E/DL001Z (GSKVx000000040996) administered in Phase 1, at Day 1.

Biological: F2F22E/DL001Z

Flu mRNA_Ph1_12 YA Group

EXPERIMENTAL

YA participants received a single dose of Flu mRNA study intervention F2F22F/DL001Z (GSKVx000000040999) administered in Phase 1, at Day 1.

Biological: F2F22F/DL001Z

Control Ph1_YA Group

ACTIVE COMPARATOR

YA participants received a single dose of Control 1 administered in Phase 1, at Day 1.

Combination Product: Control 1

Flu mRNA_Ph2_1_YA Group

EXPERIMENTAL

YA participants received a single dose of Flu mRNA study intervention F2F23D/DL001Z-NH administered in Phase 2, at Day 1.

Biological: F2F23D/DL001Z-NH

Flu mRNA_Ph2_2_YA Group

EXPERIMENTAL

YA participants received a single dose of Flu mRNA study intervention F2F23A/DL001Z-NH administered in Phase 2, at Day 1.

Biological: F2F23A/DL001Z-NH

Flu mRNA_Ph2_3_YA Group

EXPERIMENTAL

YA participants received a single dose of Flu mRNA study intervention F2F23B/DL001Z-NH administered in Phase 2, at Day 1.

Biological: F2F23B/DL001Z-NH

Control_Ph2_YA Group

ACTIVE COMPARATOR

YA participants received single dose of Control 2 vaccine administered in Phase 2, at Day 1.

Combination Product: Control 2

Flu mRNA_Ph2_1_Older adults (OA) Group

EXPERIMENTAL

OA participants received a single dose of Flu mRNA study intervention F2F23A/DL001Z-NH administered in Phase 2, at Day 1.

Biological: F2F23A/DL001Z-NH

Flu mRNA_Ph2_2_OA Group

EXPERIMENTAL

OA participants received a single dose of Flu mRNA study intervention F2F23B/DL001Z-NH administered in Phase 2, at Day 1.

Biological: F2F23B/DL001Z-NH

Flu mRNA_Ph2_3_OA Group

EXPERIMENTAL

OA participants received a single dose of Flu mRNA study intervention F2F23C/DL001Z-NH administered in Phase 2, at Day 1.

Biological: F2F23C/DL001Z-NH

Control_Ph2_OA Group

ACTIVE COMPARATOR

OA participants received a single dose of Control 3 vaccine administered in Phase 2, at Day 1.

Combination Product: Control 3

Interventions

F2C22C/DL001Z BIOLOGICAL

Study intervention was administered intramuscularly in Phase 1, at Day 1.

Flu mRNA_Ph1_1 Younger Adults (YA) Group

F2B22A/DL001Z BIOLOGICAL

Study intervention was administered intramuscularly in Phase 1, at Day 1.

Flu mRNA_Ph1_2 YA Group

F2B22B/DL001Z BIOLOGICAL

Study intervention was administered intramuscularly in Phase 1, at Day 1.

Flu mRNA_Ph1_3 YA Group

F2B22C/DL001Z BIOLOGICAL

Study intervention was administered intramuscularly in Phase 1, at Day 1.

Flu mRNA_Ph1_4 YA Group

F2B22D/DL001Z BIOLOGICAL

Study intervention was administered intramuscularly in Phase 1, at Day 1.

Flu mRNA_Ph1_5 YA Group

F2B22E/DL001Z BIOLOGICAL

Study intervention was administered intramuscularly in Phase 1, at Day 1.

Flu mRNA_Ph1_6 YA Group

F2F22A/DL001Z BIOLOGICAL

Study intervention was administered intramuscularly in Phase 1, at Day 1.

Flu mRNA_Ph1_7 YA Group

F2F22B/DL001Z BIOLOGICAL

Study intervention was administered intramuscularly in Phase 1, at Day 1.

Flu mRNA_Ph1_8 YA Group

F2F22C/DL001Z BIOLOGICAL

Study intervention was administered intramuscularly in Phase 1, at Day 1.

Flu mRNA_Ph1_9 YA Group

F2F22D/DL001Z BIOLOGICAL

Study intervention was administered intramuscularly in Phase 1, at Day 1.

Flu mRNA_Ph1_10 YA Group

F2F22E/DL001Z BIOLOGICAL

Study intervention was administered intramuscularly in Phase 1, at Day 1.

Flu mRNA_Ph1_11 YA Group

Control 1 COMBINATION_PRODUCT

Control vaccine was administered intramuscularly in Phase 1, at Day 1.

Control Ph1_YA Group

F2F23D/DL001Z-NH BIOLOGICAL

Study intervention was administered intramuscularly in Phase 2, at Day 1.

Flu mRNA_Ph2_1_YA Group

F2F23A/DL001Z-NH BIOLOGICAL

Study intervention was administered intramuscularly in Phase 2, at Day 1.

Flu mRNA_Ph2_1_Older adults (OA) Group; Flu mRNA_Ph2_2_YA Group

F2F23B/DL001Z-NH BIOLOGICAL

Study intervention was administered intramuscularly in Phase 2, at Day 1.

Flu mRNA_Ph2_2_OA Group; Flu mRNA_Ph2_3_YA Group

Control 2 COMBINATION_PRODUCT

Control vaccine was administered intramuscularly in Phase 2, at Day 1.

Control_Ph2_YA Group

F2F23C/DL001Z-NH BIOLOGICAL

Study intervention was administered intramuscularly in Phase 2, at Day 1.

Flu mRNA_Ph2_3_OA Group

Control 3 COMBINATION_PRODUCT

Control vaccine was administered intramuscularly in Phase 2, at Day 1.

Control_Ph2_OA Group

F2F22F/DL001Z BIOLOGICAL

Study intervention was administered intramuscularly in Phase 1, at Day 1.

Flu mRNA_Ph1_12 YA Group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• CureVac: collaborator

Study Sites (41)

GSK Investigational Site

Hialeah, Florida, 33012, United States

Location

GSK Investigational Site

Miami, Florida, 33186, United States

Location

GSK Investigational Site

Chicago, Illinois, 60640, United States

Location

GSK Investigational Site

Valparaiso, Indiana, 46383, United States

Location

GSK Investigational Site

Lenexa, Kansas, 66219, United States

Location

GSK Investigational Site

Wichita, Kansas, 67207, United States

Location

GSK Investigational Site

Lexington, Kentucky, 40509, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02215, United States

Location

GSK Investigational Site

Dearborn, Michigan, 48127, United States

Location

GSK Investigational Site

Papillion, Nebraska, 68046, United States

Location

GSK Investigational Site

Rochester, New York, 14609, United States

Location

GSK Investigational Site

Syracuse, New York, 13057, United States

Location

GSK Investigational Site

Denver, North Carolina, 80110, United States

Location

GSK Investigational Site

Greensboro, North Carolina, 27408, United States

Location

GSK Investigational Site

Raleigh, North Carolina, 27612, United States

Location

GSK Investigational Site

Wilmington, North Carolina, 28401, United States

Location

GSK Investigational Site

Dayton, Ohio, 33147, United States

Location

GSK Investigational Site

East Greenwich, Rhode Island, 02818, United States

Location

GSK Investigational Site

Knoxville, Tennessee, 37909, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76135, United States

Location

GSK Investigational Site

Houston, Texas, 48076, United States

Location

GSK Investigational Site

Tomball, Texas, 77375, United States

Location

GSK Investigational Site

Newport News, Virginia, 23606, United States

Location

GSK Investigational Site

Norfolk, Virginia, 23502, United States

Location

GSK Investigational Site

Antwerp, 2000, Belgium

Location

GSK Investigational Site

Edegem, 2610, Belgium

Location

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Ieper, 8900, Belgium

Location

GSK Investigational Site

Kluisbergen, 9690, Belgium

Location

GSK Investigational Site

Mechelen, 2800, Belgium

Location

GSK Investigational Site

Tielt, Belgium

Location

GSK Investigational Site

Zwalm, 9630, Belgium

Location

GSK Investigational Site

Halifax, Nova Scotia, B3K 6R8, Canada

Location

GSK Investigational Site

Truro, Nova Scotia, B2N 1L2, Canada

Location

GSK Investigational Site

Chicoutimi, Quebec, G7H 7Y8, Canada

Location

GSK Investigational Site

Québec, Quebec, G1W 4R4, Canada

Location

GSK Investigational Site

Sherbrooke, Quebec, J1L 0H8, Canada

Location

GSK Investigational Site

Buffalo, 5201, South Africa

Location

GSK Investigational Site

Cape Town, 7530, South Africa

Location

GSK Investigational Site

Johannesburg, 2113, South Africa

Location

GSK Investigational Site

Tembisa, 1632, South Africa

Location

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Phase 2 of this study will be observer blind.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2023
• First Posted: April 21, 2023
• Study Start: April 27, 2023
• Primary Completion: July 2, 2024
• Study Completion: December 18, 2024
• Last Updated: July 23, 2025
• Results First Posted: July 23, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

US (24); CA (5); BE (8); ZA (4)