Evaluation of Immunogenicity, Safety, and Reactogenicity of RSVPreF3 OA Vaccine in Adults Aged 60+ with Respiratory Syncytial Virus Infections

The primary objective of this study is to evaluate the **humoral immune response** following a 1-dose primary schedule of the RSVPreF3 OA investigational vaccine up to 12 months post-Dose 1. This is clinically relevant as it assesses the vaccine's ability to elicit an immune response against **Respiratory Syncytial Virus Infections**, which is crucial for determining its potential effectiveness in preventing the disease in adults aged 60 years and above.

Secondary objectives include:

• Further evaluation of the humoral immune response following a 1-dose primary schedule of the RSVPreF3 OA investigational vaccine up to 12 months post-Dose 1.
• Evaluation of the humoral immune response following 1 dose of the RSVPreF3 OA investigational vaccine and following revaccination doses, up to study end.
• Evaluation of the **CMI response** following 1 dose of the RSVPreF3 OA investigational vaccine and following revaccination doses up to study end.
• Evaluation of the safety and reactogenicity of each vaccination schedule of the RSVPreF3 OA investigational vaccine in all participants.

The clinical trial involves a total of **912 participants** who are being studied to evaluate the humoral immune response following a 1-dose primary schedule of the RSVPreF3 OA investigational vaccine. The study population includes both **male and female participants** aged 60 years and older, residing either in the community or in long-term care facilities. Participants are required to be medically stable, as determined by the investigator, and may have chronic stable medical conditions such as diabetes, hypertension, or cardiac disease. The trial does not include a vulnerable population. Participants were selected based on their ability to comply with the study protocol, including completing diary cards and attending regular phone calls or study site visits. The study does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is a **phase 3**, randomized, open-label, multi-country study designed to evaluate the **immunogenicity**, safety, reactogenicity, and persistence of a single dose of the RSVPreF3 OA investigational vaccine in adults aged 60 years and above. The trial aims to assess the humoral immune response following a one-dose primary schedule of the vaccine up to 12 months post-vaccination. The study will involve participants who are either community-dwelling or residing in long-term care facilities, provided they are medically stable and can comply with the study requirements. The trial is expected to conclude by May 21, 2026, with participant recruitment having commenced on February 22, 2021.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, medical stability, and ability to comply with the protocol. Following the initial vaccination on Day 1, participants will have follow-up visits at 30 days post-vaccination (Day 31), and at 6 and 12 months post-vaccination (Months 6 and 12) to assess the primary endpoint of humoral immune response, including neutralizing titers against RSV-A and RSV-B. Secondary endpoints will be evaluated at additional time points, including Months 18, 24, 30, 36, 42, 48, 54, and 60, as well as one month after each revaccination dose at Months 13, 25, 37, and 49. The end-of-study visit will occur at Month 60, marking the completion of the participant's involvement in the trial.

The expected length of participant involvement is approximately five years, with conditions for early termination including withdrawal of consent, non-compliance with study procedures, or any adverse events that, in the opinion of the investigator, warrant discontinuation. The investigational product, Arexvy, is administered via **intramuscular use** and is not a pediatric formulation. The study is not classified as low intervention, and the investigational product is not designated as an orphan drug. The trial is conducted under the sponsorship of GlaxoSmithKline Biologicals S.A., with the investigational product being a recombinant, adjuvanted vaccine targeting **respiratory syncytial virus infections**.

The clinical trial involves the administration of **Arexvy**, a **Respiratory Syncytial Virus (RSV) vaccine** that is recombinant and adjuvanted. The vaccine is presented as a **powder and suspension for suspension for injection**. The active substance in the vaccine is **Respiratory Syncytial Virus, Glycoprotein F, recombinant, stabilised in the pre-fusion conformation, adjuvanted with AS01E**. The vaccine is manufactured by GlaxoSmithKline Biologicals S.A. and is administered via **intramuscular use**. The dosage for the trial is set at a maximum of 120 micrograms per day, with a total maximum dose of 120 micrograms. The treatment period is limited to a single administration.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the immunogenicity, safety, reactogenicity, and persistence of the investigational vaccine. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The trial aims to assess the humoral immune response following a one-dose primary schedule of the RSVPreF3 OA investigational vaccine up to 12 months post-administration.

Efficacy in this clinical trial will be assessed by evaluating the **humoral immune response** following a single-dose primary schedule of the RSVPreF3 OA investigational vaccine. The primary endpoints include measuring neutralizing titers against RSV-A and RSV-B at pre-vaccination (Day 1), 30 days post-Dose 1 (Day 31), and at 6 and 12 months post-Dose 1 (Months 6 and 12) in a subset of participants. Secondary endpoints involve assessing RSVPreF3-binding Immunoglobulin G (IgG) antibody concentrations at the same timepoints, as well as at Months 18, 24, 30, 36, 42, 48, 54, and 60 post-Dose 1, and at 1 month after each revaccination dose (Months 13, 25, 37, and 49). Additionally, the cellular-mediated immune (CMI) response will be evaluated by measuring the frequency of RSVPreF3-specific CD4+ and/or CD8+ T cells expressing at least two activation markers, including at least one cytokine among CD40L, 4-1BB, IL-2, TNFa, IFNg, IL-13, and IL-17, at similar timepoints.

The occurrence of solicited administration site and systemic events will be monitored during a 4-day follow-up period after each vaccination, while unsolicited adverse events (AEs) will be recorded during a 30-day follow-up period. Serious adverse events (SAEs) and potential immune-mediated diseases (pIMDs) will be tracked up to 6 months after each vaccination, with fatal SAEs, related SAEs, and related pIMDs being documented from the first vaccination up to the study's end at Month 60. These assessments will be conducted using validated laboratory tests and patient-reported outcomes to ensure accurate and reliable data collection throughout the trial duration.