A Study on the Immune Response and Safety of a Vaccine Against Respiratory Syncytial Virus Given to Adults 50-59 Years of Age, Including Adults at Increased Risk of Respiratory Syncytial Virus Lower Respiratory Tract Disease, Compared to Older Adults 60 Years of Age and Above

NCT05590403 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 2192382022-001981-36
• Study Type: interventional
• Target: 1,544
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of this study is to demonstrate the non-inferiority (NI) of the immune response and evaluate safety of RSVPreF3 older adults (OA) investigational vaccine in adults 50-59 years of age (YOA), including those who are at increased risk (AIR) of respiratory syncytial virus (RSV)-lower respiratory tract disease (LRTD), versus adults \>=60 YOA

Conditions

Respiratory Syncytial Virus Infections

Keywords

Respiratory syncytial virus; Immunogenicity; Safety; Increased risk of respiratory syncytial virus lower respiratory tract disease; Adults aged 50-59 years of age; Older adults 60 years of age and above

Outcome Measures

Primary Outcomes (8)

• RSV-A Neutralization Titers Expressed as Group Geometric Mean Titer (GMT) in Healthy Participants Compared to OA-RSV Group

  Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. The corresponding antibody titers were expressed in Estimated Dilution 60 (ED60) and were measured on blood samples collected from vaccinated subjects. The ANCOVA model used to calculate the adjusted GMTs for RSV-A neutralizing antibodies included the baseline value as covariate (i.e. GMTs are adjusted for the PRE timepoint values) and only included Adult HA-RSV and OA-RSV groups in the model as fixed effect, as specified in Statistical Analysis Plan.

  At 1 month after the RSVPreF3 OA vaccine administration (Day 31)

• RSV-A Neutralization Titers Expressed as Group Seroresponse Rate (SRR) Difference in Healthy Participants Compared to OA-RSV Group

  The SRR is defined as the proportion of participants having a fold increase in neutralization titers (1 month post-study intervention administration over pre-study intervention administration) greater than or equal to 4 (\>=4).

  At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31) compared to baseline (Day 1)

• RSV-B Neutralization Titers Expressed as Group GMT in Healthy Participants Compared to OA-RSV Group

  Serological assays for the determination of antibodies against RSV-B were performed by neutralization assay. The corresponding antibody titers were expressed in ED60. The ANCOVA model used to calculate the adjusted GMTs for RSV-B neutralizing antibodies included the baseline value as covariate (i.e. GMTs are adjusted for the PRE timepoint values) and only included Adult HA-RSV and OA-RSV groups in the model as fixed effect, as specified in Statistical Analysis Plan.

  At 1 month after the RSVPreF3 OA vaccine administration (Day 31)

• RSV-B Neutralization Titers Expressed as Group SRR in Healthy Participants Compared to OA-RSV Group

  The SRR is defined as the proportion of participants having a fold increase in neutralization titers (1 month post-study intervention administration over pre-study intervention administration) \>=4.

  At 1 month after the RSVPreF3 OA vaccine administration (Day 31) compared to baseline (Day 1)

• RSV-A Neutralization Titers Expressed as Group GMT Titer in Participants at Increased Risk of RSV-LRTD (Adults-AIR-RSV Group) Compared to OA-RSV Group

  Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay. The corresponding antibody titers were expressed in ED60. The ANCOVA model used to calculate the adjusted GMTs for RSV-A neutralizing antibodies included the baseline value as covariate (i.e. GMTs are adjusted for the PRE timepoint values) and only included Adult AIR-RSV and OA-RSV groups in the model as fixed effect, as specified in Statistical Analysis Plan.

  At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31)

• RSV-A Neutralization Titers Expressed as Group SRR in Participants at Increased Risk of RSV-LRTD (Adults-AIR-RSV Group) Compared to OA-RSV Group

  The SRR is defined as the proportion of participants having a fold increase in neutralization titers (1 month post-study intervention administration over pre-study intervention administration) \>=4.

  At 1 month after the RSVPreF3 OA vaccine administration (Day 31) compared to baseline (Day 1)

• RSV-B Neutralization Titers Expressed as Group GMT in Participants at Increased Risk of RSV-LRTD (Adults-AIR-RSV Group) Compared to OA-RSV Group

  Serological assays for the determination of antibodies against RSV-B are performed by neutralization assay. The corresponding antibody titers were expressed in ED60. The ANCOVA model used to calculate the adjusted GMTs for RSV-B neutralizing antibodies included the baseline value as covariate (i.e. GMTs are adjusted for the PRE timepoint values) and only included Adult AIR-RSV and OA-RSV groups in the model as fixed effect, as specified in Statistical Analysis Plan.

  At 1 month after the RSVPreF3 OA vaccine administration (Day 31)

• RSV-B Neutralization Titers Expressed as Group SRR in Participants at Increased Risk of RSV-LRTD (Adults-AIR-RSV Group) Compared to OA-RSV Group

  The SRR is defined as the proportion of participants having a fold increase in neutralization titers (1 month post-study intervention administration over pre-study intervention administration) \>=4.

  At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31) compared to baseline (Day 1)

Secondary Outcomes (16)

• Percentage of Participants Reporting Each Solicited Administration Site Event (Pain, Redness and Swelling)

  During the 4-day follow up period after vaccination (vaccine or placebo administered on Day 1)

• Percentage of Participants Reporting Each Solicited Systemic Event (Fever, Headache, Muscle Pain, Joint Pain, Tiredness)

  During the 4-day follow up period after vaccination (vaccine or placebo administered on Day 1)

• Percentage of Participants Reporting Any Unsolicited Adverse Events (AEs)

  During the 30-day follow up period after vaccination (vaccine or placebo administered on Day 1)

• Percentage of Participants Reporting Any Serious Adverse Events (SAEs) Within 6 Months of Vaccination

  From the day of the vaccination up to 6 months after vaccination (vaccine or placebo administered on Day 1)

• Percentage of Participants Reporting Any Onset Potential Immune Mediated Diseases (pIMDs) Within 6 Months of Vaccination

  From the day of the vaccination up to 6 months after vaccination (vaccine or placebo administered on Day 1)

Study Arms (5)

Adults HA-RSV Group

EXPERIMENTAL

Healthy adults or adults with chronic stable conditions with or without treatment that do not lead to an increased risk of RSV-Lower respiratory tract disease (RSV-LRTD), aged 50-59 years old received 1 dose of RSVPreF3 OA vaccine at Day 1 and were followed until study end.

Biological: RSVPreF3 OA investigational vaccine

Adults HA-Placebo Group

PLACEBO COMPARATOR

Healthy adults or adults with chronic stable conditions with or without treatment that do not lead to an increased risk of RSV-LRTD, aged 50-59 years old received 1 dose of placebo at Day 1 and were followed until study end.

Drug: Placebo

Adults AIR-RSV Group

EXPERIMENTAL

Adults at increased risk of RSV-Lower respiratory tract disease (RSV-LRTD) aged 50-59 years old received 1 dose of RSVPreF3 OA vaccine at Day 1 and were followed until study end.

Biological: RSVPreF3 OA investigational vaccine

Adults AIR-Placebo Group

PLACEBO COMPARATOR

Adults at increased risk of RSV-LRTD aged 50-59 years old received 1 dose of placebo at Day 1 and were followed until study end.

Drug: Placebo

OA-RSV Group

EXPERIMENTAL

Older adults aged 60 years old and above received 1 dose of RSVPreF3 OA vaccine at Day 1 and were followed until study end.

Biological: RSVPreF3 OA investigational vaccine

Interventions

RSVPreF3 OA investigational vaccine BIOLOGICAL

One dose administered intramuscularly at Day 1.

Adults AIR-RSV Group; Adults HA-RSV Group; OA-RSV Group

Placebo DRUG

One dose administered intramuscularly at Day 1.

Adults AIR-Placebo Group; Adults HA-Placebo Group

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol
• Written or witnessed informed consent obtained from the participant prior to performance of any study-specific procedure.
• A male or female participant 50-59 YOA at the time of the study intervention administration.
• Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as hysterectomy, bilateral oophorectomy, bilateral salpingectomy or post-menopause.
• Female participants of childbearing potential may be enrolled in the study, if the participant:
• has practiced adequate contraception from 1 month prior to study intervention administration until study end for this study, and
• has a negative pregnancy test on the day of study intervention administration.
• Healthy participants as established by medical history and clinical examination before entering into the study.
• Participants with chronic stable medical conditions with or without specific treatment, such as hypertension, hypercholesterolemia, or hypothyroidism, and who are not at increased risk for RSV-LRTD , are allowed to participate in this study if considered by the investigator as medically stable (no changes in the treatment or disease severity in the past 3 months).
• Participants should be diagnosed with at least 1 of the following medical conditions and have a stable condition (no changes in the treatment or disease severity in the past 3 months):
• Chronic pulmonary disease resulting in activity restricting symptoms or use of long-term medication
• Chronic cardiovascular disease
• Diabetes mellitus: types 1 and 2
• Other diseases at increased risk for RSV-LRTD disease
• Chronic kidney disease

You may not qualify if:

• 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 intervention.
• Hypersensitivity to latex.
• 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. Study participants may decide to assign a caregiver to help them complete the study procedures.
• 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 intervention during the period beginning 30 days before the dose of study intervention (Day -29 to Day 1), or planned use during the study period (up to Visit 4, Month 12).
• Planned or actual administration of a vaccine not foreseen by the study protocol in the period starting 30 days before and ending 30 days after the dose of study intervention administration, with the exception of inactivated and subunit influenza vaccines or COVID-19 vaccines (fully licensed or with EUA) which can be administered up to 14 days before or from 14 days after the study intervention administration.
• Note: In case an emergency mass vaccination for an unforeseen public health threat 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, including investigational RSV vaccines.
• Chronic administration of immune-modifying drugs (defined as more than 14 consecutive days in total) and/or administration of long-acting immune modifying treatments or planned administration at any time up to the end of the study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Related Publications (2)

• Ferguson M, Schwarz TF, Nunez SA, Rodriguez-Garcia J, Mital M, Zala C, Pek B, Schmitt B, Toursarkissian N, Ochoa Mazarro D, Grosskopf J, Voors-Pette C, Mehta H, Amare Hailemariam H, Gerard C, Damaso S, David MP, Descamps D, Hill J, Vandermeulen C, Hulstrom V. Immune persistence and safety of the AS01E-adjuvanted respiratory syncytial virus prefusion F protein-based vaccine in adults 50-59 years of age, including at-increased-risk adults: A randomized controlled trial. Hum Vaccin Immunother. 2025 Dec;21(1):2579335. doi: 10.1080/21645515.2025.2579335. Epub 2025 Nov 5.

  PMID: 41194599 DERIVED

• Ferguson M, Schwarz TF, Nunez SA, Rodriguez-Garcia J, Mital M, Zala C, Schmitt B, Toursarkissian N, Mazarro DO, Grosskopf J, Voors-Pette C, Mehta H, Hailemariam HA, de Heusch M, Salaun B, Damaso S, David MP, Descamps D, Hill J, Vandermeulen C, Hulstrom V; RSV OA=ADJ-018 Study Group. Noninferior Immunogenicity and Consistent Safety of Respiratory Syncytial Virus Prefusion F Protein Vaccine in Adults 50-59 Years Compared to >/=60 Years of Age. Clin Infect Dis. 2024 Oct 15;79(4):1074-1084. doi: 10.1093/cid/ciae364.

  PMID: 39099093 DERIVED

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Observer-blind for Cohort 1 (Day1-Day 31) and single-blind afterwards and open-label for Cohort 2
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2022
• First Posted: October 21, 2022
• Study Start: October 28, 2022
• Primary Completion: March 13, 2023
• Study Completion: February 12, 2024
• Last Updated: March 6, 2025
• Results First Posted: May 21, 2024

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.