Evaluation of Immunogenicity and Safety of RSVPreF3 OA Vaccine in Adults Aged 60+ Following Revaccination Schedules in a Phase 3b Extension Study
- Trial ID
- 2023-509762-38-00
- Protocol
- 222090
- Sponsor
- GlaxoSmithKline Biologicals
Trial statistics
Objectives
The primary objective of this study is to evaluate the **humoral immune response** following a single revaccination dose of the RSVPreF3 OA vaccine in adults aged 60 years and above. This evaluation is conducted in two groups: the RSV_PreS4 group, which receives the vaccine at pre-Season 4, and the RSV_PreS5 group, which receives it at pre-Season 5. Understanding the immune response is clinically relevant as it provides insights into the vaccine's efficacy in inducing a protective immune response against **Respiratory Syncytial Virus Infections**, which are particularly concerning in older adults due to their increased vulnerability.
The secondary objectives include: - For the RSV_1dose group, assessing the **humoral immune persistence** induced by the initial dose of the RSVPreF3 OA vaccine administered at the start of the RSV OA=ADJ-006 study. - For all participants, evaluating the safety of each vaccination schedule. These objectives are crucial for determining the long-term effectiveness and safety profile of the vaccine, ensuring that it provides sustained protection without adverse effects.
Participants
The clinical trial involves a total of **7,382 participants** who are being studied for their response to a vaccine targeting **Respiratory Syncytial Virus Infections**. The study population includes both male and female participants, with age categories ranging from adults to older adults. Participants were selected based on their previous enrollment in the RSV OA=ADJ-006 study, where they either received a placebo or a single dose of the RSVPreF3 OA vaccine. All participants are required to be medically stable at the time of study entry, and those with chronic stable medical conditions such as diabetes, hypertension, or cardiac disease are eligible to participate. The trial does not include a vulnerable population, and participants are expected to comply with study requirements, including the completion of diary cards and attending regular study visits. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is a **phase 3b**, randomized, open-label, multi-country, multi-center study designed to evaluate the **immunogenicity** and safety of different revaccination schedules and the persistence of a single dose of the RSVPreF3 OA vaccine in adults aged 60 years and above. Participants in this study are those who previously participated in the RSV OA=ADJ-006 study. The trial aims to assess the **humoral immune response** following a single revaccination dose of the RSVPreF3 OA vaccine administered at pre-Season 4 and pre-Season 5. The study is expected to commence recruitment on August 1, 2024, and conclude by September 30, 2026.
The trial involves several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as previous participation in the RSV OA=ADJ-006 study and medical stability. Participants will then receive the vaccine via **intramuscular injection**. Follow-up visits are scheduled to monitor the **neutralizing titers** of RSV-A and RSV-B at various intervals, including 30 days post-revaccination and pre-Season 5 and 6. The primary endpoints focus on the measurement of RSV-A and RSV-B neutralizing titers and their fold increase over time. Secondary endpoints include the occurrence of unsolicited adverse events (AEs) and serious adverse events (SAEs) within specified periods post-vaccination.
Participant involvement is expected to last up to 6 months post-vaccination, with regular follow-up visits and phone calls to ensure compliance with the study protocol. Conditions that may lead to early termination from the study include non-compliance with protocol requirements or the occurrence of significant adverse events. The study is not classified as low intervention, and the trial phase is categorized as phase 3, with a focus on ensuring the safety and efficacy of the vaccine in the target population.
Treatment
The clinical trial involves the administration of **Arexvy**, a **Respiratory Syncytial Virus (RSV) vaccine** that is recombinant and adjuvanted. The pharmaceutical form of Arexvy is a **powder and suspension for suspension for injection**, specifically designed for intramuscular use. The active substance in Arexvy is the **Respiratory Syncytial Virus, Glycoprotein F, recombinant, stabilised in the pre-fusion conformation, adjuvanted with AS01E**. The maximum daily and total dose of the vaccine is 120 micrograms, administered as a single dose. The treatment period is limited to one day, and the vaccine is not formulated for pediatric use. The vaccine is manufactured by GlaxoSmithKline Biologicals S.A. and is authorized for use in the European Union under the marketing authorization number EU/1/23/1740/001.
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 and safety of different revaccination schedules and the persistence of a single dose of the RSVPreF3 OA vaccine in adults aged 60 years and above. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The study is designed as a phase 3b, randomized, open-label, multi-country, multi-center extension and crossover vaccination study, with the primary objective of assessing the humoral immune response following revaccination.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the **humoral immune response** following revaccination with the RSVPreF3 OA vaccine in adults aged 60 years and above. The primary endpoints include measuring RSV-A and RSV-B neutralizing titers at various timepoints: before revaccination (pre-Season 4 and pre-Season 5), 30 days post-revaccination, and at pre-Season 6. The fold increase in neutralizing titers from Day 1 to Day 31, pre-Season 5, and pre-Season 6 will also be assessed. Additionally, the proportion of participants achieving a ≥4-fold increase in neutralizing titers from Day 31 over Day 1 or pre-Season 5 will be evaluated.
Secondary endpoints involve assessing RSV-A and RSV-B neutralizing titers at pre-Season 4, pre-Season 5, and pre-Season 6, as well as the occurrence of unsolicited adverse events (AEs) within 30 days post-vaccination. Serious adverse events (SAEs) and potential immune-mediated diseases (pIMDs) will be monitored from the day of vaccination up to six months post-vaccination, including any fatal SAEs. These efficacy parameters will be collected and analyzed at specified intervals to determine the vaccine's immunogenicity and safety profile.
Inclusion and Exclusion Criteria
Inclusion Criteria
- '- Male or female participants who were previously enrolled in the RSV OA=ADJ-006 study and received placebo (Placebo group) or a single dose of the RSVPreF3 OA vaccine (RSV_1dose group).
- "- Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, attend regular phone calls/study site visits, ability to access and utilize a phone or other electronic communications). Note: In case of physical incapacity that would preclude the self-completion of the diary cards, either site staff can assist the participant (for activities performed during site visits) or the participant may assign a caregiver to assist him/her with this activity (for activities performed at home or in the LTCF). However, at no time, the site staff or caregiver will evaluate the participant’s health status while answering diaries or make decisions on behalf of the participant. Refer to Section 8 and Definition of Terms of the Clinical Study Protocol for the definition of caregiver. "
- "- 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 study entry. 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.
Exclusion Criteria
- '- Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., current malignancy, human immunodeficiency virus) or immunosuppressive/cytotoxic therapy (e.g., medication used during cancer chemotherapy, organ transplantation, or to treat autoimmune disorders), 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 (For details on components of study intervention administered, refer to Arexvy SmPC/Prescribing information) [Arexvy Summary of Product Characteristics, 2023; Arexvy Prescribing Information, 2023].
- '- Hypersensitivity to latex.
- '- Serious or unstable chronic illness.
- '- 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 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. Note: If deemed necessary for clinical evaluation, the investigator can use tools such as Mini-Mental State Exam (MMSE), Mini-Cog or Montreal Cognitive Assessment (MoCA) to determine cognition levels of the participant. "
- '- Participants who experienced an SAE or pIMD from first study intervention administration in the RSV OA=ADJ-006 study until enrollment in this study that was considered to be possibly or probably related to the study vaccine or non-study concomitant vaccines, either by the investigator or the sponsor, including hypersensitivity reactions.
- '- Participants with a new onset of a pIMD or exacerbation of a pIMD from first study intervention administration in the RSV OA=ADJ-006 study until enrollment in this study, that, in the opinion of the investigator, exposes the participant to unacceptable risk from subsequent vaccination.
- '- Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study vaccine during the period beginning 30 days before the first study visit, or their planned use during the study period.
- '- Previous vaccination with an RSV vaccine (investigational or licensed vaccine) and/or planned administration of an RSV vaccine during the study period other than the RSVPreF3 OA vaccine administered during the RSV OA=ADJ-006 study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 01 Aug 2024 | 460 |
 Estonia | Not Recruiting | 01 Aug 2024 | 429 |
 Finland | Not Recruiting | 01 Aug 2024 | 540 |
 Germany | Not Recruiting | 01 Aug 2024 | 1575 |
 Italy | Not Recruiting | 01 Aug 2024 | 80 |
 Poland | Not Recruiting | 01 Aug 2024 | 1180 |
 Spain | Not Recruiting | 01 Aug 2024 | 654 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Arexvy powder and suspension for suspension for injection
Respiratory Syncytial Virus (RSV) vaccinerecombinant, adjuvanted | Test | POWDER AND SUSPENSION FOR SUSPENSION FOR INJECTION | INTRAMUSCULAR USE | 120 | 1 | PRD10447046 |