Immunogenicity of Adjuvanted RSVPreF3 Vaccine in Elderly Patients Aged 80+ and 60-65 with RSV Infection: An Open-Label Phase IIIb Study

Trial ID: 2024-520141-23-01
Protocol: RISE
Sponsor: Karolinska Institutet

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Diseases & Conditions

Respiratory syncytial virus infection

Objectives

The primary objective of this study is to describe the induction of **neutralizing antibodies** against **RSV A** and **B** following the first dose of Arexvy in older adults aged 80 years and older, as well as those aged 60 to 65 years. This is clinically relevant as it evaluates the vaccine's potential to elicit an immune response in a population at high risk for severe **RSV infection**.

Secondary objectives include:

Evaluating the reactogenicity of Arexvy by recording the occurrence of solicited adverse events (AEs) in the study participants.
Assessing the safety of Arexvy in terms of the incidence of unsolicited AEs, serious adverse events (SAEs), potential immune-mediated diseases (pIMDs), and fatal SAEs.

These objectives are crucial for understanding the vaccine's safety profile and its potential side effects in the target population.

Participants

The clinical trial focuses on evaluating the induction of neutralizing antibodies against **RSV infection** in older adults. The study population includes both male and female participants, specifically targeting two age groups: individuals aged 80 years and older, and those aged 60 to 65 years. 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 involve a vulnerable population. Participants must be able to understand and read Swedish, and they must provide written consent to receive the Arexvy vaccine. The sponsor has not provided information regarding the total number of participants in the trial.

Plans and Procedures

The clinical trial is designed to evaluate the **immunogenicity** of a vaccine targeting **RSV infection** in older adults. This is a Phase IIIb, open-label study focusing on individuals aged 60 to 65 years and those aged 80 years and older. The trial aims to assess the induction of neutralizing antibodies against RSV A and B following the administration of the Arexvy vaccine. The study is structured to include a prime dose followed by a revaccination, with the primary endpoint being the measurement of neutralizing antibody titers one month after the initial dose. Secondary endpoints include the assessment of adverse events (AEs), both solicited and unsolicited, as well as serious adverse events (SAEs) and potential immune-mediated diseases (pIMDs) over a six-month period.

The trial employs a controlled design, with participants being randomly assigned to receive the vaccine via **injection**. The study is not blinded, allowing for open observation of outcomes. The trial is expected to commence recruitment on April 14, 2025, and conclude by June 30, 2027, with a maximum treatment period of 12 months. Participants will be involved in the study for the duration of the trial, with specific visits scheduled for screening, vaccination, follow-up, and an end-of-study assessment. The inclusion visit will confirm eligibility based on criteria such as age, ability to provide informed consent, and medical stability. Follow-up visits will monitor the occurrence and intensity of AEs, while the end-of-study visit will evaluate the overall safety and efficacy of the vaccine.

Participant involvement is expected to last up to 12 months, with conditions for early termination including withdrawal of consent, non-compliance with the protocol, or any adverse health developments deemed significant by the investigator. The study is conducted under strict adherence to ethical guidelines, ensuring the safety and well-being of all participants throughout the trial duration.

Treatment

The clinical trial involves the administration of an **experimental medication** known as the **Respiratory Syncytial Virus (RSV) Vaccine**, which contains the active substance **respiratory syncytial virus, glycoprotein F, recombinant, stabilised in the pre-fusion conformation, adjuvanted with AS01E**. This vaccine is designed to induce neutralizing antibodies against RSV A and B in older adults. The pharmaceutical form of the vaccine is denoted as PHF00243MIG. The vaccine is administered via **injection**. The dosage regimen includes a maximum daily dose of 0.5 ml and a total maximum dose of 1.0 ml over the course of the treatment period. The maximum treatment period is 12 months. The vaccine is not a paediatric formulation and is classified under the ATC code J07BX05, which pertains to respiratory syncytial virus vaccines.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of the RSV vaccine to evaluate its immunogenicity in the specified population. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The trial aims to assess the vaccine's ability to induce an immune response in the most elderly and frail population, specifically targeting individuals aged 80 years and older, as well as those aged 60 to 65 years.

Efficacy

Efficacy in this clinical trial will be assessed by evaluating the induction of neutralizing antibodies against **Respiratory Syncytial Virus (RSV)** A and B following the administration of the Arexvy vaccine. The primary endpoint involves measuring the neutralizing antibody titers one month after the prime dose (day 31) in study participants aged 60 to 65 years and those aged 80 years and older. This assessment will provide insights into the immunogenic response elicited by the vaccine in these age groups.

Secondary endpoints will include the occurrence, intensity, and duration of solicited adverse events (AEs) at the administration site and systemic AEs within a 4-day follow-up period post-vaccination. Additionally, the incidence of unsolicited AEs will be monitored during a 30-day follow-up period after each vaccination. Serious adverse events (SAEs) or potential immune-mediated diseases (pIMDs) will be tracked from the day of vaccination until six months post-vaccination. The occurrence of any fatal SAEs will be recorded from day 1 up to the study's conclusion. These endpoints will be systematically collected and analyzed to ensure a comprehensive evaluation of the vaccine's safety and efficacy profile.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Male or female individuals who were born between 1965 and 1960 or 1945 and before, at the time of the first vaccination, who live in the community or in a long-term care facility.
Individuals who can understand and read Swedish.
Individuals who can provide written consent and agree (by written consent) to receive the Arexvy vaccine.
Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
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, such as diabetes, hypertension or cardiac disease, are allowed to participate if considered by the investigator as medically stable.

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Exclusion Criteria

Individuals who are medically immunocompromised, less than 2 years since hematopoietic stem cell transplantation (HSCT) or graft-versus-host disease (GVHD), solid-organ transplanted, other immunosuppressive drugs for treatment of cancer and inflammatory mediated or autoimmune conditions, as judged by the Investigator.
Individuals who have already received an RSV vaccine dose at any time in the past.
Any known or suspected reaction, hypersensitivity or allergies to be exacerbated by any product or component included in the vaccine and trial
Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of participation in the trial.
Treatment or disease which, according to the investigator, can affect treatment or trial results.
Any of the following medical conditions: - Unstable chronic illness - Recurrent or un-controlled neurological disorders or seizures - Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study - Any other 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 - Any history of dementia or any medical condition that moderately or severely impairs cognition and understanding of the informed consent form and/or study procedures - 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
Participation in another clinical trial during the study period, or any previous clinical trials with RSV- or hMPV-vaccine or other prophylaxis.
Planned move during the study period that will prohibit participating in the study until study end.
Participation of any study personnel or their immediate dependents, family or household members as well as any family relations to Sponsor or PI.
Co-administration of other vaccines less than 14 days before or after study vaccination. A period of less than 30 days before or after study vaccination applies in the case of Shingrix.