Evaluation of Immune Response and Safety of RSVPreF3 OA and Raxtozinameran Co-administration in Adults Aged 50 and Above with Respiratory Syncytial Virus Infections
- Trial ID
- 2023-510196-59-00
- Protocol
- 217848
- Sponsor
- GlaxoSmithKline Biologicals
Trial statistics
Objectives
The primary objective of this study is to demonstrate the **non-inferiority** of the humoral immune response to the RSVPreF3 OA investigational vaccine when co-administered with a COVID-19 mRNA vaccine compared to when the RSVPreF3 OA investigational vaccine is administered alone. Additionally, the study aims to demonstrate the non-inferiority of the humoral immune response to a COVID-19 mRNA vaccine when co-administered with the RSVPreF3 OA investigational vaccine compared to when the COVID-19 mRNA vaccine is administered alone. This is clinically relevant as it evaluates the potential for simultaneous administration of these vaccines, which could enhance vaccination strategies, especially in adults aged 50 years and above.
Secondary objectives include:
- Evaluating the humoral immune response to the RSVPreF3 OA investigational vaccine when co-administered with a COVID-19 mRNA vaccine or administered alone.
- Evaluating the humoral immune response to a COVID-19 mRNA vaccine when co-administered with the RSVPreF3 OA investigational vaccine or administered alone.
- Assessing the safety and **reactogenicity** following administration of the RSVPreF3 OA investigational vaccine and a COVID-19 mRNA vaccine, whether co-administered or administered alone.
Participants
The clinical trial involves a total of **250 participants** who are being studied for their response to a vaccine targeting **Respiratory Syncytial Virus Infections**. The study population includes both male and female subjects aged **50 years and older**, who are medically stable at the time of the first vaccination. Participants may have chronic stable medical conditions such as diabetes, hypertension, or cardiac disease, provided these conditions are considered stable by the investigator. The trial population was selected based on their ability to comply with the study protocol, including completion of diary cards and attendance at follow-up visits. Participants are required to have received a SARS-CoV-2 vaccine at least three months prior to the study vaccination. The study does not include a vulnerable population, and participants are either living independently in the community or in an assisted-living facility with minimal assistance. Female participants of childbearing potential must practice adequate contraception and have a negative pregnancy test prior to study intervention. The trial aims to assess the non-inferiority of the humoral immune response when the investigational vaccine is co-administered with a COVID-19 mRNA vaccine compared to when each vaccine is administered alone.
Plans and Procedures
The clinical trial is a **Phase 3**, open-label, randomized, controlled study designed to evaluate the immune response, safety, and reactogenicity of the RSVPreF3 OA investigational vaccine when co-administered with a COVID-19 mRNA vaccine (Omicron XBB.1.5) in adults aged 50 years and above. The trial aims to demonstrate the non-inferiority of the humoral immune response to the RSVPreF3 OA investigational vaccine when co-administered with a COVID-19 mRNA vaccine compared to the RSVPreF3 OA investigational vaccine administered alone. Additionally, it seeks to demonstrate the non-inferiority of the humoral immune response to a COVID-19 mRNA vaccine when co-administered with the RSVPreF3 OA investigational vaccine compared to the COVID-19 mRNA vaccine administered alone.
The trial is expected to commence recruitment on July 1, 2024, and conclude by May 27, 2025. Participants will be involved in the study for a maximum treatment period of one month, with the overall study duration extending up to six months after the last study intervention administration. The study includes several key visits: an inclusion (screening) visit to assess eligibility based on criteria such as age, medical stability, and previous SARS-CoV-2 vaccination; follow-up visits to monitor immune response and safety; and an end-of-study visit to evaluate long-term outcomes. Participants will be monitored for primary endpoints, including RSV-A and RSV-B neutralization titers and SARS-CoV-2 Omicron XBB.1.5 neutralization titers, one month after vaccine administration. Secondary endpoints will assess additional immune response metrics and safety outcomes, including adverse events and serious adverse events.
Participants may be withdrawn from the study if they fail to comply with protocol requirements, experience significant adverse events, or if the investigator deems it necessary for medical reasons. The study will be conducted in accordance with ethical guidelines, and informed consent will be obtained from all participants prior to any study-specific procedures. The investigational products, Arexvy and Comirnaty Omicron XBB.1.5, will be administered intramuscularly, with a maximum daily dose of 0.5 ml and 0.3 ml, respectively. The trial is not classified as low intervention, and the data disclosure will be deferred to protect the economic interests of the sponsor.
Treatment
The clinical trial involves the administration of two experimental medications. The first medication is **Arexvy**, a **Respiratory Syncytial Virus (RSV) vaccine** (recombinant, adjuvanted), provided in the form of a powder and suspension for suspension for injection. The active substance in Arexvy is the **Respiratory Syncytial Virus, Glycoprotein F, recombinant, stabilised in the pre-fusion conformation, adjuvanted with AS01E**. This vaccine is manufactured by GlaxoSmithKline Biologicals S.A. and is administered intramuscularly. The dosage for Arexvy is 0.5 milliliters per administration, with a maximum treatment period of one day. The pharmaceutical form is a suspension for injection, and it is not a pediatric formulation.
The second medication used in the trial is **Comirnaty Omicron XBB.1.5**, a COVID-19 mRNA vaccine, provided as a dispersion for injection. The active substance in this vaccine is **Raxtozinameran**, which is a 5'-capped mRNA encoding the SARS-CoV-2 Omicron variant XBB.1.5 Spike protein, pre-fusion stabilised. This vaccine is manufactured by BioNTech Manufacturing GmbH and is also administered intramuscularly. The dosage for Comirnaty Omicron XBB.1.5 is 0.3 milliliters per administration, with a maximum treatment period of one day. The pharmaceutical form is a dispersion for injection, and it is not a pediatric formulation.
Both vaccines are administered intramuscularly, and the trial aims to evaluate the immune response, safety, and reactogenicity when these vaccines are co-administered in adults aged 50 years and above. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.
Efficacy
Efficacy in this clinical trial will be assessed through the measurement of **neutralization titers** for both Respiratory Syncytial Virus (RSV) and SARS-CoV-2 Omicron XBB.1.5 variant. The primary endpoints include the RSV-A and RSV-B neutralization titers, expressed as group Geometric Mean Titer (GMT) ratios, measured one month after the administration of the RSVPreF3 OA investigational vaccine. Additionally, the SARS-CoV-2 Omicron XBB.1.5 neutralization titers against pseudovirus bearing the S protein will be evaluated, also expressed as group GMT ratios, one month following the COVID-19 mRNA vaccine administration.
Secondary endpoints will further explore the efficacy by assessing the RSV-A and RSV-B neutralization titers expressed as GMT, Mean Geometric Increase (MGI), and Seroconversion Rate (SRR) at one month post-vaccination. The percentage of participants achieving RSV-A and RSV-B neutralizing titers equal to or above the assay cut-off at pre-vaccination and one month post-vaccination will also be determined. For the SARS-CoV-2 Omicron XBB.1.5 variant, neutralization titers will be expressed as GMT and MGI, with the percentage of participants reaching titers above the assay cut-off evaluated at similar timepoints.
Data collection will occur at specified intervals, with primary and secondary endpoints measured one month after vaccine administration. The trial will also monitor the percentage of participants reporting solicited administration site events and systemic events within four days post-vaccination, unsolicited adverse events within 30 days, and serious adverse events (SAEs) and potential immune-mediated diseases (pIMDs) up to six months after the last study intervention. These assessments will provide a comprehensive evaluation of the vaccine's efficacy and safety profile.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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, return for follow-up visits). INC#1
- Written or witnessed informed consent obtained from the participant (participant must be able to understand the informed consent) prior to performance of any study-specific procedure. INC#2
- A male/female of ≥50 YOA at the time of the first study intervention administration. INC#3
- 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 in this study if considered by the investigator as medically stable. INC#4
- 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. INC#5
- Participants who have received previously a SARS-CoV-2 vaccine, being administered at least 3 months prior to study vaccination. INC#6
- Female participants of non-childbearing potential may be enrolled in the study. Non childbearing potential is defined as hysterectomy, bilateral oophorectomy, bilateral salpingectomy, and post-menopause. INC#7
- "Female participants of childbearing potential may be enrolled in the study if the participant. INC#8 has practiced adequate contraception from 1 month prior to study intervention administration and agreed to continue adequate contraception for at least 1 month after the last vaccination. has a negative pregnancy test on the day of and prior to study intervention administration. "
Exclusion Criteria
- History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions, including a known history of severe allergic reaction (e.g., anaphylaxis). EXC#1
- 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). EXC#2
- Any history of myocarditis or pericarditis. EXC#3
- Recurrent history 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 (e.g. completion of diary cards, attend regular phone calls/study site visits). EXC#4
- Serious or unstable chronic illness. EXC#5
- Any history of dementia or any medical condition that moderately or severely impairs cognition. EXC#6
- Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study (e.g., life-threatening disease likely to limit survival up to study end). EXC#7
- Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. EXC#8
- Any SAE attributed to a previous dose of the SARS-CoV-2 mRNA vaccine. EXC#9
- Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. EXC#10
- Recent SARS-CoV-2 infection within 3 months prior to the COVID-19 vaccine dose administration. Timelines to be determined from symptoms onset or positive COVID-19 test (if infection was asymptomatic). EXC#11
- Use of any investigational or non-registered product (drug, vaccine or invasive medical device) other than the study interventions during the period beginning 30 days before the first dose of study interventions and ending 30 days after the last vaccine administration, or their planned use during the study period. EXC#12
- Planned administration of a vaccine in the period starting 30 days before the first dose and ending 30 days after the last dose of study intervention(s) administration*, with the exception of inactivated and subunit influenza vaccines which can be administered up to 14 days before or from 14 days after the study vaccination. EXC#13
- "• Chronic administration of immune-modifying drugs (defined as more than 14 consecutive days in total) and/or planned use of long-acting immune-modifying treatments at any time up to the last blood sampling visit. EXC#14 Up to 3 months prior to the study intervention administration: o For corticosteroids, this will mean prednisone equivalent ≥ 20 mg/day. Inhaled and topical steroids are allowed. o Administration of immunoglobulins and/or any blood products or plasma derivatives. Up to 6 months prior to study intervention administration: long-acting immune modifying drugs including among others immunotherapy (e.g., TNF-inhibitors), monoclonal antibodies and antitumoral medication."
- Administration of any SARS-CoV-2 vaccine during the 3 months preceding the study COVID-19 mRNA vaccine administration. EXC#15
- Previous vaccination with licensed or investigational RSV vaccine. EXC#16
- 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). EXC#17
- Pregnant or lactating female participant. EXC#18
- Female participant planning to become pregnant or planning to discontinue contraceptive precautions. EXC#19
- 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. EXC#20
- Participation of any study personnel or their immediate dependents, family, or household members. EXC#21
- Planned move during the study conduct that prohibits participation until study end. EXC#22
- Bedridden participants. EXC#23
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 01 Jul 2024 | 250 |
 The Netherlands | Not Recruiting | 01 Jul 2024 | — |
 Spain | Not Recruiting | 01 Jul 2024 | 200 |
| Netherlands | — | — | 150 |
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 | 0.5 | 1 | PRD10447046 |
Comirnaty Omicron XBB.1.5 30 micrograms/dose dispersion for injection COVID-19 mRNA Vaccine | Comparator | DISPERSION FOR INJECTION | INTRAMUSCULAR | 0.3 | 1 | PRD10813394 |