A Study on the Immune Response and Safety Elicited by a Vaccine Against Respiratory Syncytial Virus (RSV) When Given Alone and Together With a Vaccine Against Influenza in Adults Aged 65 Years and Above

A Phase 3, Open-label, Randomized, Controlled, Multicountry Study to Evaluate the Immune Response, Safety and Reactogenicity of RSVPreF3 OA Investigational Vaccine When Co-administered With FLU HD Vaccine in Adults Aged 65 Years and Above

The purpose of this study is to assess the immunogenicity, safety and reactogenicity of the RSVPreF3 OA investigational vaccine when co-administered with the high dose quadrivalent influenza (FLU HD) vaccine in adults aged 65 years and above compared to separate administration of the vaccines.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 1029
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • GSK Investigational Site
  • Arizona
    • Tempe, Arizona, United States, 85281
      • GSK Investigational Site
  • California
    • Canoga Park, California, United States, 91303
      • GSK Investigational Site
    • Colton, California, United States, 92324
      • GSK Investigational Site
    • Sacramento, California, United States, 95864
      • GSK Investigational Site
    • San Diego, California, United States, 92103-6204
      • GSK Investigational Site
    • Walnut Creek, California, United States, 94598
      • GSK Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80012
      • GSK Investigational Site
  • Florida
    • Coral Gables, Florida, United States, 33134
      • GSK Investigational Site
    • Fort Myers, Florida, United States, 33912
      • GSK Investigational Site
    • Hialeah, Florida, United States, 33012
      • GSK Investigational Site
    • Immokalee, Florida, United States, 34142
      • GSK Investigational Site
    • Miami, Florida, United States, 33016
      • GSK Investigational Site
    • Miami, Florida, United States, 33184
      • GSK Investigational Site
    • Orlando, Florida, United States, 32801
      • GSK Investigational Site
    • West Palm Beach, Florida, United States, 33409
      • GSK Investigational Site
  • Georgia
    • Sandy Springs, Georgia, United States, 30328
      • GSK Investigational Site
    • Savannah, Georgia, United States, 31406
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60640
      • GSK Investigational Site
  • Indiana
    • Evansville, Indiana, United States, 47714
      • GSK Investigational Site
    • Mishawaka, Indiana, United States, 46544
      • GSK Investigational Site
    • Valparaiso, Indiana, United States, 46383
      • GSK Investigational Site
  • Iowa
    • Ames, Iowa, United States, 50010
      • GSK Investigational Site
  • Kansas
    • El Dorado, Kansas, United States, 67042
      • GSK Investigational Site
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • GSK Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • GSK Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • GSK Investigational Site
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • GSK Investigational Site
    • Papillion, Nebraska, United States, 68046
      • GSK Investigational Site
  • Nevada
    • North Las Vegas, Nevada, United States, 89030
      • GSK Investigational Site
  • New Jersey
    • Warren, New Jersey, United States, 07059
      • GSK Investigational Site
  • North Carolina
    • Hickory, North Carolina, United States, 28601
      • GSK Investigational Site
    • Rocky Mount, North Carolina, United States, 27804
      • GSK Investigational Site
    • Wilmington, North Carolina, United States, 28401
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • GSK Investigational Site
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • GSK Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15243
      • GSK Investigational Site
  • South Carolina
    • Columbia, South Carolina, United States, 21045
      • GSK Investigational Site
    • North Charleston, South Carolina, United States, 29405
      • GSK Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • GSK Investigational Site
  • Tennessee
    • Jefferson City, Tennessee, United States, 37760
      • GSK Investigational Site
    • Memphis, Tennessee, United States, 38119
      • GSK Investigational Site
    • Nashville, Tennessee, United States, 37912
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78745
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78237
      • 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
• A male or female ≥65 years of age 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 vaccination. Participants with chronic stable medical conditions with or without specific treatment 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 vaccines.
• Hypersensitivity to latex.
• History of Guillain Barré syndrome, or anaphylaxis.
• Serious or unstable chronic illness.
• Any history of dementia or any medical condition that moderately or severely impairs cognition.
• Recurrent or un-controlled 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 (e.g. completion of diary cards, attend regular phone calls/study site visits).
• 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 study vaccine administration, 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.

Note: In case an emergency mass vaccination for an unforeseen public health threat (e.g.: a pandemic) is recommended and/or organized by the public health authorities, outside the routine immunization program, the time period described above can be reduced if necessary for that vaccine provided it is used according to the local governmental recommendations and that the Sponsor is notified accordingly.

• 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 first dose of study vaccine 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 vaccination 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 intervention (drug/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.
• Planned move during the study conduct that prohibits participation until 1 month post-last vaccine administration.
• Bedridden participants.
• 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-HD vaccine and one dose of RSVPreF3 OA vaccine, both doses administered at Day 1, and were followed until end of study.	Biological: RSVPreF3 OA investigational vaccine; RSVPreF3 OA investigational vaccine administered intramuscularly in the deltoid region of the non-dominant arm.; Biological: FLU HD vaccine; FLU HD vaccine administered intramuscularly in the deltoid region of the dominant arm (Co-Ad Group) or the non-dominant arm (Control Group).
Active Comparator: Control Group; Participants received one dose of FLU-HD vaccine at Day 1, followed by one dose of RSVPreF3 OA vaccine at Day 31, and were followed until the study end.	Biological: RSVPreF3 OA investigational vaccine; RSVPreF3 OA investigational vaccine administered intramuscularly in the deltoid region of the non-dominant arm.; Biological: FLU HD vaccine; FLU HD vaccine administered intramuscularly in the deltoid region of the dominant arm (Co-Ad Group) or the non-dominant arm (Control Group).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RSV-A Neutralizing Titers Expressed as Group Geometric Mean Titers (GMTs)	RSV-A neutralizing titers were given as group GMTs and expressed as Estimated Dilution 60 (ED60).	At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group)
Hemagglutinin Inhibition (HI) Titers for 4 FLU Vaccine Strains Expressed as Group GMTs	HI titers were assessed 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 strains.	At 1 month after the FLU vaccine dose (Day 31 for both groups)
RSV-B Neutralizing Titers Expressed as Group GMTs	RSV-B neutralizing titers were given as group GMTs and expressed as Estimated Dilution 60 (ED60).	At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for the Co-Ad 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 titers was 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 Neutralizing 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 Neutralizing 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)
HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT	HI titers were assessed 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 strains. HI antibodies were expressed as GMTs, in titers.	At Day 1 and 1 month after FLU vaccine dose administration (Day 31 for both groups)
HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains	SPR for HI titers was defined as the percentage of participants with a serum HI titer >= 1:40. The assessed Flu strains were: 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 and 1 month after FLU vaccine dose administration (Day 31 for both groups)
HI 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.	At 1 month after the FLU vaccine dose administration (Day 31 for both groups)
Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration	The solicited administration site events after vaccination included erythema, pain and swelling.	Within 4 days (the day of vaccination and 3 subsequent days) after each vaccination (administered on Day 1 and 31)
Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration	The solicited systemic events after vaccination include arthralgia, fatigue, fever, headache and myalgia.	Within 4 days (the day of vaccination and 3 subsequent days) after each vaccination (administered on Day 1 and 31)
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 diary. Unsolicited events must have been 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 after vaccine administration (the day of vaccination and 29 subsequent days after vaccination)
Percentage 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 disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant.	From Day 1 up to study end (6 months after last vaccination - Month 6 for Co-Ad Group and Month 7 for Control group)
Percentage of Participants Reporting 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 up to study end (6 months after last vaccination - Month 6 for Co-Ad Group and Month 7 for Control group)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Buynak R, Cannon K, DeAtkine D, Kirby J, Usdan L, Bhavsar A, Gerard C, Kuznetsova A, Jayadev A, Amare H, Valenciano S, Meyer N. Randomized, Open-Label Phase 3 Study Evaluating Immunogenicity, Safety, and Reactogenicity of RSVPreF3 OA Coadministered with FLU-QIV-HD in Adults Aged >/= 65. Infect Dis Ther. 2024 Aug;13(8):1789-1805. doi: 10.1007/s40121-024-00985-4. Epub 2024 Jun 26.

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2022
• Primary Completion (Actual): March 7, 2023
• Study Completion (Actual): August 15, 2023

Study Registration Dates

• First Submitted: September 26, 2022
• First Submitted That Met QC Criteria: September 26, 2022
• First Posted (Actual): September 29, 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; Adults aged 65 years and above; High dose quadrivalent influenza vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Respiratory Syncytial Virus Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 214489; 2021-001356-34 (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.: Yes