A Study on the Immune Response and Safety of a Vaccine Against Respiratory Syncytial Virus (RSV) When Given Alone or Co-administered With an Adjuvanted Vaccine Against Influenza in Adults Aged 65 Years and Above

A Phase III, Open-label, Randomized, Controlled, Multi-country Study to Evaluate the Immune Response, Safety and Reactogenicity of an RSVPreF3 OA Investigational Vaccine When Co-administered With FLU aQIV (Inactivated Influenza Vaccine - Adjuvanted) in Adults Aged 65 Years and Above

The aim of this study is to assess the immunogenicity, safety and reactogenicity of the RSV PreFusion protein 3 older adult (RSVPreF3 OA) investigational vaccine when co-administered with an adjuvanted quadrivalent influenza (FLU aQIV) vaccine, in adults aged 65 years of age (YOA).

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus Infections
• Intervention / Treatment: Biological: FLU vaccine; Biological: RSVPreF3 OA vaccine

• Study Type: Interventional
• Enrollment (Actual): 1045
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • GSK Investigational Site
  • Erpent, Belgium, 5101
    • GSK Investigational Site
  • Genk, Belgium, 3600
    • GSK Investigational Site
  • Ieper, Belgium, 8900
    • GSK Investigational Site
• Finland
  • Espoo, Finland, 02230
    • GSK Investigational Site
  • Helsinki, Finland, 00100
    • GSK Investigational Site
  • Kokkola, Finland, 67100
    • GSK Investigational Site
  • Oulu, Finland, 90220
    • GSK Investigational Site
  • Seinajoki, Finland, 60100
    • GSK Investigational Site
  • Tampere, Finland, 33100
    • GSK Investigational Site
• France
  • Angers, France, 49000
    • GSK Investigational Site
  • Clermont-Ferrand Cedex 1, France, 63003
    • GSK Investigational Site
  • Limoges Cedex, France, 87042
    • GSK Investigational Site
  • Lyon cedex 04, France, 69317
    • GSK Investigational Site
  • Montpellier cedex 5, France, 34295
    • GSK Investigational Site
  • Nîmes cedex 9, France, 30029
    • GSK Investigational Site
  • Paris, France, 75679
    • GSK Investigational Site
  • Pierre-Bénite, France, 69495
    • GSK Investigational Site
• Spain
  • Benalmádena, Málaga, Spain, 29630
    • GSK Investigational Site
  • Boadilla Del Monte (Madrid), Spain, 28660
    • GSK Investigational Site
  • Burgos, Spain, 09006
    • GSK Investigational Site
  • Centelles, Spain, 08540
    • GSK Investigational Site
  • La Roca Del Valles (Barcelona), Spain, 08430
    • GSK Investigational Site
  • Madrid, Spain, 28006
    • GSK Investigational Site
  • Madrid, Spain, 28040
    • GSK Investigational Site
  • Salamanca, Spain, 37007
    • GSK Investigational Site
  • Santander (Cantabria), Spain, 39008
    • GSK Investigational Site
  • Valladolid, Spain, 47005
    • GSK Investigational Site
  • Vic, Spain, 28500
    • GSK Investigational Site
  • Andalucia
    • Marbella - Málaga, Andalucia, Spain, 29603
      • GSK Investigational Site
• United Kingdom
  • Blackpool, United Kingdom, FY3 7EN
    • GSK Investigational Site
  • Bristol, United Kingdom, BS37 4AX
    • GSK Investigational Site
  • Chippenham, United Kingdom, SN14 6GT
    • GSK Investigational Site
  • Peterborough, United Kingdom, PE8 6PL
    • GSK Investigational Site
  • Cambridgeshire
    • Soham, Cambridgeshire, United Kingdom, CB7 5JD
      • GSK Investigational Site
  • Cheshire
    • Bollington, Cheshire, United Kingdom, SK10 5JH
      • GSK Investigational Site
  • Wiltshire
    • Chippenham, Wiltshire, United Kingdom, SN15 2SB
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the electronic diary cards [eDiaries], return for follow-up visits, ability to access and utilize a phone or other electronic communications).
• A male or female ≥ 65 YOA at the time of the first study intervention administration.
• Participants living in the general community or in an assisted-living facility that provides minimal assistance, such that the participant is primarily responsible for self-care and activities of daily living.
• Written or witnessed informed consent obtained from the participant prior to performance of any study-specific procedure.
• Participants who are medically stable in the opinion of the investigator at the time of first study intervention administration. Participants with chronic stable medical conditions with or without specific treatment, such as diabetes, hypertension or cardiac disease, are allowed to participate in this study if considered by the investigator as medically stable.

Exclusion Criteria:

Medical conditions

• Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy, 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 interventions, in particular any history of severe allergic reaction to egg protein or to a previous influenza vaccine.
• Hypersensitivity to latex.
• Guillain-Barré syndrome that occurred within 6 weeks of receipt of prior influenza vaccine.
• Serious or unstable chronic illness.
• Any history of dementia or any medical condition that moderately or severely impairs cognition.
• Recurrent or uncontrolled neurological disorders or seizures. Participants with medically-controlled active or chronic neurological diseases can be enrolled in the study as per investigator assessment, provided that their condition will allow them to comply with the requirements of the protocol.
• Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study.
• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.

Prior/Concomitant therapy

• Use of any investigational or non-registered product (drug, vaccine, or medical device) other than the study interventions during the period beginning 30 days before the first dose of study interventions, or planned use during the study period.
• Administration of an influenza vaccine during the 6 months preceding the study FLU vaccine administration.
• Planned or actual administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first study intervention administration and ending 30 days after the last study intervention administration. In the case of COVID-19 vaccines, this time window can be decreased to 14 days before and after each study intervention administration provided this COVID-19 vaccine use is in line with local governmental recommendations.
• Previous vaccination with an RSV vaccine.
• Administration of long-acting immune-modifying drugs or planned administration 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 administration of first dose of study interventions or planned administration during the study period.
• Chronic administration (defined as more than 14 consecutive days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the first study intervention dose or planned administration during the study period. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed.

Prior/Concurrent clinical study experience

• 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 vaccine/product (drug or invasive medical device).

Other exclusions

• History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures.
• Bedridden participants.
• Planned move during the study conduct that prohibits participation until study end.
• Participation of any study personnel or their immediate dependents, family, or household members.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Co-Ad Group; Participants received one dose of FLU-aQIV vaccine and one dose of RSVPreF3 OA vaccine, both doses administered at Day 1, and were followed until end of study.	Biological: FLU vaccine; One dose of FLU vaccine administered intramuscularly.; Other Names: Fluad Tetra, FLUAD QUADRIVALENT, Fluad Quad; Biological: RSVPreF3 OA vaccine; One dose of RSVPreF3 OA vaccine administered intramuscularly.
Active Comparator: Control Group; Participants received one dose of FLU-aQIV vaccine at Day 1, followed by one dose of RSVPreF3 OA vaccine at Day 31, and were followed until end of study.	Biological: FLU vaccine; One dose of FLU vaccine administered intramuscularly.; Other Names: Fluad Tetra, FLUAD QUADRIVALENT, Fluad Quad; Biological: RSVPreF3 OA vaccine; One dose of RSVPreF3 OA vaccine administered intramuscularly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titers for Hemagglutination Inhibition (HI) Antibodies Against 4 FLU Vaccine Strains Expressed as Group Geometric Mean Titers (GMTs) at 1 Month After FLU Vaccine Dose	HI antibodies assessed were antibodies against the Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata flu strains.	At 1 month after the FLU vaccine dose (Day 31 for both groups)
RSV-A Neutralizing Antibody Titers Expressed as GMTs	RSV-A neutralizing antibodies were given as GMTs and expressed as Estimated Dilution 60 (ED60).	At 1 month after the RSVPreF3 OA dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group)
RSV-B Neutralizing Antibody Titers Expressed as GMTs	RSV B neutralizing antibodies are given as GMTs and expressed as Estimated Dilution 60 (ED60).	At 1 month after the RSVPreF3 OA dose (Day 31 for the CoAd Group and Day 61 for the Control Group)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains	SCR for HI antibody is defined as the percentage of participants who have either a HI predose titer less than (<) 1:10 and a post-dose titer greater than or equal to (>=) 1:40, or a pre-dose titer >= 1:10 and at least a 4-fold increase in post-dose titer. The assessed Flu strains were: Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata.	At 1 month after the FLU vaccine dose (Day 31 for both groups)
RSV-A Neutralization Antibody Titers Expressed as Mean Geometric Increase (MGI)	MGI was defined as the geometric mean of the within-participant ratios of the post-dose titer over the pre-dose titer.	At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group) compared to pre-vaccination (Day 1 for Co-Ad group and Day 31 for Control group)
RSV-B Neutralization Antibody Titers Expressed as MGI	MGI was defined as the geometric mean of the within-participant ratios of the post-dose titer over the pre-dose titer.	At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group) compared to pre-vaccination (Day 1 for Co-Ad group and Day 31 for Control group)
Titers for HI Antibodies Against 4 FLU Vaccine Strains	HI antibodies assessed were antibodies against the Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata flu strains. HI antibodies were expressed as GMT, in titers.	At Day 1 (Baseline) and Day 31
HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains	SPR for HI antibody was defined as the percentage of participants with a serum HI titer >= 1:40. The assessed Flu strains were: Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata.	At Day 1 (Baseline) and Day 31
HI Antibody Titers for 4 FLU Vaccine Strains Expressed as MGI	MGI was defined as the geometric mean of the within-participant ratios of the post-dose titer over the pre-dose titer. The assessed Flu strains were: Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata.	At 1 month after the FLU dose (Day 31 for both groups) compared to pre-vaccination (Day 1 for both groups)
Percentage of Participants Reporting Each Solicited Administration Site Event After Each Vaccine Dose Administration	The solicited administration site events after vaccination include erythema, pain and swelling.	Within 7 days (the day of vaccination and 6 subsequent days) after each vaccine administration (vaccines administered at Day 1 for CoAd Group and at Day 1 and Day 31 for Control group)
Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration	The solicited systemic events after vaccination include fever, headache, fatigue, myalgia and arthralgia.	Within 7 days (the day of vaccination and 6 subsequent days) after each vaccine administration (vaccines administered at Day 1 and Day 31 for C-oAd Group and at Day 1 and Day 31 for Control group)
Percentage of Participants Reporting Unsolicited Adverse Events (AEs)	An unsolicited AEs is an AE that is not included in a list of solicited events using a Participant Electronic Diary. Unsolicited events must be spontaneously communicated by a participant who signs the informed consent. Unsolicited AEs include both serious, non-serious AEs and potential immune-mediated diseases (pIMDs).	Within 30 days (the day of vaccination and 29 subsequent days) after each vaccine administration
Percentage of Participants Reporting at Least One Serious Adverse Event (SAEs)	An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study participant.	From Day 1 until 6 months after last vaccination (Month 6 for the Co-Ad Group, Month 7 for the Control group)
Percentage of Participants Reporting at Least One Potential Immune-mediated Disease (pIMDs)	pIMDs are a subset of AEs of special interest that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. The investigator must exercise his/her medical/scientific judgment to determine whether other diseases have an autoimmune origin (i.e., pathophysiology involving systemic or organ-specific pathogenic autoantibodies) and should also be recorded as a pIMD.	From Day 1 until 6 months after last vaccination (Month 6 for the Co-Ad Group, Month 7 for the Control group)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Clark R, Davies S, Labrador J, Loubet P, Natalini Martinez S, Morinigo HM, Nicolas JF, Vera MP, Ramet M, Rebollo-Rodrigo MH, Sanz-Munoz I, Dezutter N, Germain S, David MP, Jayadev A, Hailemariam HA, Kotb S, Meyer N. Safety and Immunogenicity of Respiratory Syncytial Virus Prefusion F Protein Vaccine when Co-administered with Adjuvanted Seasonal Quadrivalent Influenza Vaccine in Older Adults: A Phase 3 Randomized Trial. Clin Infect Dis. 2024 Aug 5:ciae365. doi: 10.1093/cid/ciae365. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2022
• Primary Completion (Actual): February 17, 2023
• Study Completion (Actual): July 17, 2023

Study Registration Dates

• First Submitted: October 3, 2022
• First Submitted That Met QC Criteria: October 3, 2022
• First Posted (Actual): October 6, 2022

Study Record Updates

• Last Update Posted (Actual): September 24, 2024
• Last Update Submitted That Met QC Criteria: September 9, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Respiratory syncytial virus; Reactogenicity; Adjuvanted quadrivalent influenza vaccine; Adults aged 65 years and above
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Paramyxoviridae Infections; Mononegavirales Infections; Orthomyxoviridae Infections; Pneumovirus Infections; Influenza, Human; Respiratory Syncytial Virus Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 218350; 2022-000623-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: GSK will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf
• IPD Sharing Time Frame: Anonymized IPD is 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No