Evaluation of Immune Response and Safety of RSVPreF3 OA Vaccine in Lung and Renal Transplant Recipients and Healthy Controls
- Trial ID
- 2023-503951-81-00
- Protocol
- 219900
- Sponsor
- GlaxoSmithKline Biologicals
Trial statistics
Objectives
The primary objective of this study is to evaluate the **humoral immune response** against Respiratory Syncytial Virus (RSV) subtypes A and B following the administration of the RSVPreF3 OA investigational vaccine in renal and lung solid organ transplant (SOT) patients. This evaluation will be conducted after both the first and second doses within the 2-dose group. Understanding the immune response in this population is clinically relevant as these patients are at increased risk for severe RSV infections, and effective vaccination could significantly reduce morbidity and mortality associated with RSV.
Secondary objectives include: - Evaluating the **humoral immune response** to the RSVPreF3 OA investigational vaccine up to 12 months post-administration in all groups, and assessing the cell-mediated immune (CMI) response in a subset of participants. - Evaluating the safety and reactogenicity of the RSVPreF3 OA investigational vaccine in all groups. These secondary objectives are crucial for determining the long-term efficacy and safety profile of the vaccine, which is essential for its potential use in vulnerable populations.
Participants
The clinical trial involves a total of **245 participants** who are being evaluated for their humoral immune response to the RSVPreF3 OA investigational vaccine. The study population includes both male and female subjects, with age ranges starting from 18 years for renal and lung transplant patients and 50 years for healthy participants. The participants are either renal or lung transplant patients who have received an ABO compatible allograft more than 12 months prior to the study and are on maintenance immunosuppressive therapy, or they are healthy individuals with stable chronic conditions such as diabetes mellitus, hypertension, or cardiac disease. The trial population was selected based on specific inclusion criteria, ensuring that participants are medically stable and capable of complying with study requirements. Lifestyle considerations such as diet and physical activity are not specified, but participants are expected to be primarily responsible for their self-care and daily activities. The study does not involve a vulnerable population, and both genders are equally represented.
Plans and Procedures
The clinical trial is a **Phase 2b**, randomized, controlled, open-label study designed to evaluate the immune response and safety of the RSVPreF3 OA investigational vaccine in adults aged 18 years and older who have undergone lung or renal transplantation. The study aims to compare the effects of one versus two doses of the vaccine in transplant recipients and to assess the response in healthy controls aged 50 years and above receiving a single dose. The trial is expected to commence recruitment on November 7, 2023, and conclude by August 13, 2025.
Participants will be randomly assigned to receive either one or two doses of the vaccine, administered via **intramuscular injection**. The study will include several key visits: an initial screening visit to determine eligibility, followed by vaccination visits, and subsequent follow-up visits to monitor immune response and safety. The primary endpoints focus on measuring RSV-A and RSV-B serum neutralizing titers post-vaccination in transplant recipients. Secondary endpoints include additional immunogenicity assessments and safety evaluations, such as the frequency of adverse events and serious adverse events.
The expected duration of participant involvement is approximately one year, with conditions for early termination including non-compliance with study procedures or the occurrence of significant adverse events. Participants will be required to comply with study protocols, including attending all scheduled visits and completing necessary documentation. The study will ensure that participants are medically stable and capable of adhering to the trial requirements, with specific inclusion criteria for transplant recipients and healthy controls. The trial will provide valuable insights into the vaccine's efficacy and safety in a population at increased risk for **Respiratory Syncytial Virus Infections**.
Treatment
The clinical trial involves the administration of **Arexvy**, a **Respiratory Syncytial Virus (RSV) vaccine** that is recombinant and adjuvanted. The vaccine is 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**, which is recombinant and stabilized in the pre-fusion conformation, adjuvanted with AS01E. The vaccine is administered via **intramuscular use**. The maximum daily dose is 120 micrograms, with a total maximum dose of 240 micrograms. The treatment period is limited to one day. The vaccine is manufactured by GlaxoSmithKline Biologicals S.A. and is not a pediatric formulation.
In this study, Arexvy is compared to standard-of-care therapy, which includes a control group receiving a single dose of the vaccine. The trial is designed to evaluate the immune response and safety of the investigational vaccine in adults aged 18 years and older, specifically targeting lung and renal transplant recipients. The study also includes healthy controls aged 50 years and older who receive one dose of the vaccine. Compliance with the dosing schedule is monitored throughout the trial to ensure accurate assessment of the vaccine's efficacy and safety.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the humoral immune response against **Respiratory Syncytial Virus (RSV)**. The primary endpoints include measuring RSV-A and RSV-B serum neutralizing titers, expressed as Mean Geometric Increase (MGI) post-Dose 2 over post-Dose 1 in renal and lung solid organ transplant (SOT) patients within the 2-dose group. Secondary endpoints will further assess immunogenicity by evaluating RSV-A and RSV-B serum neutralizing titers expressed as Geometric Mean Titers (GMT) at pre-study and all post-study intervention visits in all participants. Additionally, the Cellular Mediated Immunity (CMI) response will be measured as group GMT of the frequency of RSVPreF3-specific CD4+ and/or CD8+ T cells at pre- and all post-study visits in a subset of participants.
Inclusion and Exclusion Criteria
Inclusion Criteria
- "Inclusion criteria for all participants: • Participants and/or participant’s parent(s)/LAR(s) who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the paper diary cards, return for follow-up visits, ability to access and utilize a phone or other electronic communications, have regular contact to allow evaluation during the study). • Participants living in the general community or in an assisted-living facility that provides minimal assistance can be enrolled, such that the participant is primarily responsible for self-care and activities of daily living. •Written or witnessed informed consent obtained from the participant/participant’s parent(s)/LARs (participant must be able to understand the informed consent) prior to performance of any study-specific procedure. • Female participants of nonchildbearing potential may be enrolled in the study. Non childbearing potential is defined as hysterectomy, bilateral oophorectomy, bilateral salpingectomy, and 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 and agreed to continue adequate contraception until study end for this study, and - has a negative pregnancy test on the day of and prior to study intervention administration. Refer to protocol section 10.4.1 for definitions of women of childbearing potential, non childbearing potential, menarche and menopause and protocol section 10.4.2 on adequate contraception. "
- "Specific inclusion criteria for renal/lung transplant patients: •A male or female participant, ≥18 YoA at the time of signing the Informed consent form (ICF) or Informed assent form (IAF). •Written informed assent obtained from the participant (participant must be able to understand the informed assent) if he/she is less than legal age of consent*, or written informed consent obtained from the participant if the participant has achieved legal age of consent. • Participant who has received an ABO compatible allogeneic renal or lung transplant (allograft) more than 12 months (365 days) prior to the first study intervention administration. • Participant receiving maintenance immunosuppressive therapy for the prevention of allograft rejection. "
- Specific inclusion criteria for renal transplant (RTx) patients: Participant with stable renal function, stability defined as less than 20% variability between last two results of eGFR or in the opinion of the investigator after investigator review of more than the last two results of eGFRs and based on medical history.
- Specific inclusion criteria for lung transplant (LTx) patients: Participant with stable lung function, with stability defined as the stability in the FEV1 compared to post-transplant baseline FEV1 and based on medical history of the last 3 months, in the opinion of the investigator.
- "Specific inclusion criteria for healthy participants: • A male or female, ≥50 YoA at the time of signing the Informed consent form (ICF). • Healthy participants as established by medical history and clinical examination before entering the study. • Participants who are medically stable in the opinion of the investigator at the time of first study intervention administration. • Participants with chronic stable medical conditions with or without specific treatment, such as diabetes mellitus, hypertension, or cardiac disease, are allowed to participate in this study if considered by the investigator as medically stable. "
Exclusion Criteria
- "Medical conditions for all: •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 the study protocol and Arexvy SmPC/Prescribing information). • Acute or chronic clinically significant cardiovascular or hepatic functional abnormality as determined by physical examination or laboratory screening tests. • Recurrent or uncontrolled neurological disorders or seizures. Participants with medically controlled 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 the diary cards, attend study site visits). Study participants may decide to assign a caregiver to help them complete some of the study procedures (Refer protocol section 8). • Any history of dementia or any medical condition that moderately or severely impairs cognition. • Any condition which, in the judgment of the investigator, would make IM injection unsafe. • 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). • Acute disease and/or fever at the time of study intervention administration. Fever is defined as temperature ≥ 38°C /100.4°F determined by oral or axillary route. However, participants with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator. • Bedridden participants. • Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study."
- "Prior/Concomitant therapy for all: • Use of any investigational or non-registered product (drug, vaccine, or medical device) other than the study intervention administration during the period beginning 30 days before the first dose of study intervention administration (Day -30 to Day 1), or their planned use during the study period (up to Visit 6). • Previous vaccination with the same antigen (RSV) containing vaccine as that of the study intervention, including investigational RSV vaccines. • Planned or actual administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose of study intervention administration and ending 30 days after the last dose of study intervention administration*. In the case of COVID-19 and inactivated/subunit/split influenza vaccines, this time window can be decreased to 14 days before and after each study intervention administration."
- "Prior/Concurrent clinical study experience for all: • 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). "
- "Other exclusion criteria for all: • Pregnant or lactating female participant. • Female participant planning to become pregnant or planning to discontinue contraceptive precautions. • 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 of any study personnel or their immediate dependents, family, or household members. • Planned move during the study period that will prohibit participating in the study until study end. "
- "Specific exclusion criteria for renal/lung transplant patients: • More than one organ transplanted (i.e., kidney-liver or kidney-other organ(s) transplanted). Dual organ is allowed (double kidney or double lung). • History of events that, in the opinion of the investigator, may put the participant at increased risk for chronic allograft dysfunction. • Participant with an episode of allograft rejection over the previous 3 months (90 days) prior to the first study intervention administration. • Histologic evidence of chronic allograft injury. • Active treatment for acute rejection. • Current diagnosis of malignancy (except non-melanoma skin cancer that does not require systemic therapy). • Any autoimmune conditions or pIMDs that in the opinion of the investigator may put the participant at increased risk. • Any confirmed or suspected HIV infection or primary immunodeficiency disease or ongoing CMV infection with a viremia > 200 IU/mL. • Use of anti-CD20 or other B-cell monoclonal antibody agents (e.g., rituximab) as induction, maintenance and/or therapeutic immunosuppressive therapy for the prevention of allograft rejection within 9 months (274 days) of first dose of study. • Use of investigational and non-registered immunosuppressants at the local/country level, unless specifically prescribed for the prevention of allograft rejection, and which are non-registered and: available locally through compassionate use programs, submitted for and pending local/country registration, approved and registered for use in other countries with well-documented SmPC or Prescribing Information. The name of the active component(s) of these immunosuppressants must be provided in the concomitant medication listing. • Evidence or high suspicion, in the opinion of the investigator, of noncompliance or nonadherence to use of induction and/or maintenance immunosuppressive therapies. • Any clinically significant* hematologic (hemoglobin level, white blood cell, lymphocyte, neutrophil, eosinophil, platelet red blood cell count and erythrocyte mean corpuscular volume) and/or biochemical (ALT, AST, creatinine, blood urea nitrogen) laboratory abnormality. Specific exclusion criteria for renal transplant (RTx) patients: • Previous allograft loss secondary to recurrent primary kidney disease. Multiple consecutive kidney transplants are allowed if the reason for a previous allograft loss is not recurrent primary kidney disease. • Evidence of significant proteinuria/albuminuria in the opinion of the investigator. Specific exclusion criteria for lung transplant (LTx) patients: • At study intervention administration visit, diagnosis of documented acute pulmonary infection within the 2 prior weeks, based on the following: clinical, radiological, and physiological deterioration; OR isolation of an organism from a clinically relevant BAL fluid culture. • Patients with diagnosis of chronic lung allograft dysfunction, defined as a decrement of 20% or more in FEV1 compared to post-transplant baseline FEV1. "
- "Specific exclusion criteria for healthy participants: • Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., current malignancy, HIV) 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). • Unstable serious chronic illness. • 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. Up to 3 months prior to the study intervention administration: *For corticosteroids, this will mean prednisone equivalent ≥20 mg/day, or equivalent. Inhaled, topical and intra-articular steroids are allowed. **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, antitumoral medication."
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 07 Nov 2023 | 21 |
 Italy | Not Recruiting | 07 Nov 2023 | 32 |
 Spain | Not Recruiting | 07 Nov 2023 | 77 |
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 | PRD10447593 |