A Study on the Safety, Reactogenicity and Immune Response of a Vaccine Against Influenza in Healthy Younger and Older Adults

A Phase 1 Randomized, Dose Escalation Study to Evaluate the Safety, Reactogenicity and Immunogenicity of an mRNA-based Monovalent Influenza Vaccine Candidate in Healthy Younger and Older Adults

The purpose of this first-time-in-human (FTiH) study is to assess the safety, reactogenicity and immunogenicity of GlaxoSmithKline's (GSK) messenger RNA (mRNA)-based monovalent vaccine (GSK4382276A) candidate against influenza in healthy younger adults (YA) and older adults (OA).

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Biological: GSK4382276A Dose level 1; Biological: GSK4382276A Dose level 2; Biological: GSK4382276A Dose level 3; Biological: GSK4382276A Dose level 4; Biological: GSK4382276A Dose level 5; Biological: GSK4382276A Dose level 6; Biological: GSK4382276A Dose level 7; Biological: GSK4382276A Dose level 8; Biological: GSK4382276A Dose level 9; Biological: GSK4382276A Dose level 10; Combination product: FDQ21A-NH; Combination product: FDQ22A-NH

• Study Type: Interventional
• Enrollment (Actual): 324
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • GSK Investigational Site
  • Ghent, Belgium, 9000
    • GSK Investigational Site
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3J 3G9
      • GSK Investigational Site
  • Quebec
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • GSK Investigational Site
• Spain
  • Madrid, Spain, 28006
    • GSK Investigational Site
  • Madrid, Spain, 28046
    • GSK Investigational Site
  • Madrid, Spain, 28222
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• A male or female between and including 18 and 45 years of age (YAs) or between and including 60 and 80 years of age (OAs) at the time of the study intervention administration. The age of sentinel participants in OA category will be limited to maximum 70 years.
• Healthy or medically stable participants as established by medical history, safety laboratory assessments and clinical examination.
• Body mass index >= 18 kg/m^2 and <= 32 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

• Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or review of the participant's medical record.

• Any clinically significant hematological coagulation or urine analysis laboratory abnormality.

  * The investigator should use his/her clinical judgement to decide which abnormalities are clinically significant.

• Current or past malignancy, unless completely resolved without 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).
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention (including latex, poly-ethylene-glycol, egg protein and aminoglycoside antibiotics).
• Recurrent history or uncontrolled neurological disorders or seizures, including Guillain-Barré syndrome and Bell's palsy, with the exception of febrile seizures during childhood.
• 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.
• Significant exposure to persons with influenza or laboratory-confirmed SARS-CoV-2 within 7 days prior to Visit 1 (Day 1) and for whom a SARS-CoV-2 PCR test has not (yet) been confirmed as negative.

Prior/Concomitant therapy

• Administration of seasonal influenza vaccine within 180 days before enrollment or planned administration up to Visit 4 (Day 29).

• 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 28 days after the study intervention administration*, with the exception of vaccines authorized or approved for the prevention of COVID-19 (regardless of the type of vaccine).

  *In case emergency mass vaccination for an unforeseen public health threat is 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 mass vaccination 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 SARS-CoV-2 virus, 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 mg/day. Inhaled, topical and intraarticular steroids are allowed.
• Previous enrolment in this study.

Other exclusions

• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions within the 1-month post-dosing period.
• History of abusive alcohol and/or drug consumption in the past 5 years.
• 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.
• Previous enrollment in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Flu mRNA_Dose level 1_Younger adults (YA); On Day 1, YA adult participants received Flu mRNA at Dose Level 1, the lowest concentration evaluated in the study.	Biological: GSK4382276A Dose level 1; Single dose of intervention administered at Day 1; Other Names: Flu mRNA
Experimental: Flu mRNA_Dose level 2 _YA; On Day 1, YA participants received Flu mRNA at Dose Level 2, which corresponds to a higher concentration than Dose Level 1.	Biological: GSK4382276A Dose level 2; Single dose of intervention administered at Day 1; Other Names: Flu mRNA
Experimental: Flu mRNA_Dose level 3_YA; On Day 1, YA participants received Flu mRNA at Dose Level 3, which corresponds to a higher concentration than Dose Level 2.	Biological: GSK4382276A Dose level 3; Single dose of intervention administered at Day 1; Other Names: Flu mRNA
Experimental: Flu mRNA_Dose level 4_YA; On Day 1, YA participants received Flu mRNA at Dose Level 4, which corresponds to a higher concentration than Dose Level 3.	Biological: GSK4382276A Dose level 4; Single dose of intervention administered at Day 1; Other Names: Flu mRNA
Experimental: Flu mRNA_Dose level 5_YA; On Day 1, YA participants received Flu mRNA at Dose Level 5, which corresponds to a higher concentration than Dose Level 4.	Biological: GSK4382276A Dose level 5; Single dose of intervention administered at Day 1; Other Names: Flu mRNA
Experimental: Flu mRNA_Dose level 6_YA; On Day 1, YA participants received Flu mRNA at Dose Level 6, which corresponds to a higher concentration than Dose Level 5.	Biological: GSK4382276A Dose level 6; Single dose of intervention administered at Day 1; Other Names: Flu mRNA
Experimental: Flu mRNA_Dose level 7_YA; On Day 1, YA participants received Flu mRNA at Dose Level 7, which corresponds to a higher concentration than Dose Level 6.	Biological: GSK4382276A Dose level 7; Single dose of intervention administered at Day 1; Other Names: Flu mRNA
Experimental: Flu mRNA_ Dose level 8_YA; On Day 1, YA participants received Flu mRNA at Dose Level 8, which corresponds to a higher concentration than Dose Level 7.	Biological: GSK4382276A Dose level 8; Single dose of intervention administered at Day 1; Other Names: Flu mRNA
Experimental: Flu mRNA_Dose level 9_YA; On Day 1, YA participants received Flu mRNA at Dose Level 9, which corresponds to a higher concentration than Dose Level 8.	Biological: GSK4382276A Dose level 9; Single dose of intervention administered at Day 1; Other Names: Flu mRNA
Experimental: Flu mRNA_Dose level 10_YA; On Day 1, YA participants received Flu mRNA at Dose Level 10, the highest concentration evaluated in the study.	Biological: GSK4382276A Dose level 10; Single dose of intervention administered at Day 1; Other Names: Flu mRNA
Active Comparator: Pooled Control_YA; On Day 1, YA participants received a single dose of FDQ21A - NH or FDQ22A -NH administered as a control and were analyzed together as pooled group throughout the study.	Combination product: FDQ21A-NH; Single dose of intervention administered at Day 1; Combination product: FDQ22A-NH; Single dose of intervention administered at Day 1
Experimental: Flu mRNA_Dose level 7_Older adults (OA); On Day 1, OA participants received Flu mRNA at Dose Level 7.	Biological: GSK4382276A Dose level 7; Single dose of intervention administered at Day 1; Other Names: Flu mRNA
Active Comparator: Control_OA; On Day 1, OA participants received a single dose of FDQ21A-NH administered at as a control.	Combination product: FDQ21A-NH; Single dose of intervention administered at Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting Any Solicited Administration Site Events	Assessed solicited administration site events included pain, erythema/redness, swelling and 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.	Day 1 to Day 7
Number of Participants Reporting Any Solicited Systemic Events	Assessed solicited systemic events included fever, chills, headache, myalgia, arthralgia and fatigue. Any = occurrence of the symptom regardless of intensity grade.	Day 1 to Day 7
Number of Participants Reporting Any Unsolicited Adverse Events (AEs)	An unsolicited AEs is an AEs 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 must have been communicated by a participant who has signed the informed consent or through his/her caregiver. Unsolicited AEs include both serious and non-serious AEs. Any = occurrence of the symptom regardless of intensity grade or relation to study vaccination.	Day 1 to Day 28
Number of Participants Reporting Serious Adverse Events (SAEs)	An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, or resulted in abnormal pregnancy outcomes, or in other situations that were considered serious per medical or scientific judgment.	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).	Day 1 to Day 183
Number of Participants Reporting 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, Clinical Chemistry, Coagulation and Urine Analysis	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 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,Clinical Chemistry, Coagulation and Urine Analysis	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 Titers (GMT) of Anti-vaccine Antibody Titers		At Day 1
GMT of Anti-vaccine Antibody Titers		At Day 22
Geometric Mean Increase (GMI) of Anti-vaccine Antibody Titers From Day 1 (Baseline) to Day 22	GMI is defined as the geometric mean of the ratios of the post-dose anti-vaccine antibody titers over the Day 1 anti-vaccine antibody titers.	From Day 1 to Day 22
Percentage of Participants With Anti-vaccine 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.	From Day 1 to Day 22
Percentage of Participants With Anti-vaccine Antibody Seroprotection Rate (SPR)	SPR is defined as the percentage of dosed participants with a anti-vaccine antibody titer ≥ 1:40.	At Day 22

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMT of Anti-vaccine Antibody Titers		At Day 62 and Day 183
GMI of Anti-vaccine Antibody Titers From Day 1 (Baseline) to Day 62	GMI is defined as the geometric mean of the ratios of the post-dose anti-vaccine antibody titer over the Day 1 anti-vaccine antibody titer.	From Day 1 to Day 62
GMI of Anti-vaccine Antibody Titers From Day 1 (Baseline) to Day 183	GMI is defined as the geometric mean of the ratios of the post-dose anti-vaccine antibody titer over the Day 1 anti-vaccine antibody titer.	From Day 1 to Day 183
Percentage of Participants With Anti-vaccine Antibody SPR	SPR is defined as the percentage of dosed participants with a anti-vaccine antibody titers ≥ 1:40.	At Day 62 and Day 183

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: CureVac
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Publications and helpful links

General Publications

• Leroux-Roels I, De Coster I, Borobia AM, Langley JM, Ochoa Mazarro D, Ruiz-Antoran B, Berre S, Germain S, Knauer C, Koch SD, Mann P, Mesia Vela D, Ovbude LJ, Pardo IA, Srivastava B, Moldt B, Nordgren M. Safety and immunogenicity of an investigational mRNA-lipid nanoparticle-based monovalent influenza vaccine: Results from a phase 1, randomized, dose-escalation study. Hum Vaccin Immunother. 2026 Dec;22(1):2631804. doi: 10.1080/21645515.2026.2631804. Epub 2026 Feb 17.

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2022
• Primary Completion (Actual): March 26, 2024
• Study Completion (Actual): March 26, 2024

Study Registration Dates

• First Submitted: June 28, 2022
• First Submitted That Met QC Criteria: July 4, 2022
• First Posted (Actual): July 7, 2022

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Influenza; Immunogenicity; Reactogenicity; mRNA vaccine; Healthy older adults; Healthy younger adults
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human
• Other Study ID Numbers: 217895; 2022-000489-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No