A Study on the Immune Response and Safety of an RSV Vaccine When Given to Adults 18 Years of Age and Above Who Received Lung or Kidney Transplant and Are at an Increased Risk of Respiratory Syncytial Virus Lower Respiratory Tract Disease and Compared to Healthy Adults 50 Years of Age and Above

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immunogenicity, safety, and reactogenicity of the RSVPreF3 OA investigational vaccine in an immunocompromised (lung and renal transplant recipients) population and assess whether a second dose of the vaccine increases the immune response.

Official Title
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A Phase 2b, Randomized, Controlled, Open-label Study to Evaluate the Immune Response and Safety of the RSVPreF3 OA Investigational Vaccine in Adults (>=18 Years of Age) When Administered to Lung and Renal Transplant Recipients Comparing 1 Versus 2 Doses and Compared to Healthy Controls (>=50 Years of Age) Receiving 1 Dose

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Biological: RSVPreF3 OA Investigational Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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)/LAR(s) (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. Specific inclusion criteria for renal/lung transplant patients: A male or female, >=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 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: History of any reaction/ hypersensitivity likely to be exacerbated by any component of the study intervention. Acute or chronic clinically significant cardiovascular or hepatic functional abnormality as determined by physical examination or laboratory screening tests. Recurrent/uncontrolled neurological disorders or seizures. Participants with medically controlled chronic neurological diseases can be enrolled in the study if their condition will allow them to comply with the requirements of the protocol, with the help of a caregiver if needed. Any history of dementia or any medical condition that moderately or severely impairs cognition. Any condition which would make IM injection unsafe. Significant underlying illness that would prevent completion of the study). Acute disease and/or fever at the time of study intervention administration (>=38°C /100.4°F, oral or axillary). Participants with a minor illness without fever may be enrolled at the discretion of the investigator. Bedridden participants. Prior/Concomitant therapy: Use of any other investigational or non-registered product (drug, vaccine, or medical device) up to 30 days before the first dose administration (Day -30 to Day 1), or their planned use during the study period (up to Visit 6). Previous vaccination with the study antigen (RSV), including investigational RSV vaccines. Unexpected vaccine administration during a study should not occur 30 days prior to the first dose or 30 days after the last dose. For COVID-19 and inactivated/subunit/split influenza vaccines, this window is shortened to 14 days. Prior/Concurrent clinical study experience: • Concurrently participating in another active clinical study Other exclusion criteria: 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 Participation of any study personnel or their immediate dependents. 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. Dual organ is allowed. History of events that may put the participant at increased risk for chronic allograft dysfunction. Participant with an episode of allograft rejection over the previous 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 may put the participant at increased risk. Any confirmed or suspected HIV infection, primary immunodeficiency disease or ongoing CMV infection with a viremia >200 IU/mL. Use of anti-CD20 or other B-cell monoclonal antibody agents for the prevention of allograft rejection within 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 in process of approval, approved in other countries and locally available. Evidence/high suspicion\ of noncompliance/nonadherence to use of induction and/or maintenance immunosuppressive therapies. Any clinically significant hematologic and/or biochemical laboratory abnormality. Specific exclusion criteria for RTx patients: Previous allograft loss secondary to recurrent primary kidney disease. Multiple consecutive kidney transplants are allowed if the reason is not recurrent primary kidney disease. Evidence of significant proteinuria/albuminuria. Specific exclusion criteria for LTx patients: At study intervention administration visit, diagnosis of documented acute pulmonary infection within the 2 prior weeks. Patients with diagnosis of chronic lung allograft dysfunction (decrement of >=20% in FEV1 compared to post-transplant baseline FEV1). Specific exclusion criteria for healthy participants: Any confirmed/suspected immunosuppressive/immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy, based on medical history and physical examination. Unstable serious chronic illness. Chronic administration of immune-modifying drugs (>14 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 -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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RSV_IC_1 group<br>Immunocompromised (IC) patients receiving 1 dose of RSVPreF3 OA investigational vaccine at Visit 1 (Day 1). | Biological: RSVPreF3 OA Investigational Vaccine<br>* The investigational vaccine will be administered intramuscularly as 1 dose to RSV_IC_1 and RSV_HA groups, and 2 doses to RSV_IC_2 group).<br>|
| Experimental: RSV_IC_2 group<br>Immunocompromised (IC) patients receiving 2 doses of RSVPreF3 OA investigational vaccine at Visit 1 (Day 1) and Visit 3 (Visit 1 + 30-60 days). | Biological: RSVPreF3 OA Investigational Vaccine<br>* The investigational vaccine will be administered intramuscularly as 1 dose to RSV_IC_1 and RSV_HA groups, and 2 doses to RSV_IC_2 group).<br>|
| Active Comparator: RSV_HA group<br>Healthy participants receiving 1 dose of RSVPreF3 OA investigational vaccine at Visit 1 (Day 1). | Biological: RSVPreF3 OA Investigational Vaccine<br>* The investigational vaccine will be administered intramuscularly as 1 dose to RSV_IC_1 and RSV_HA groups, and 2 doses to RSV_IC_2 group).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RSV-A serum neutralizing titers expressed as mean geometric increase (MGI) post Dose 2 over post-Dose 1 | The analysis is performed on the renal and lung SOT patients in the 2-dose group. | At Visit 4 (Visit 3 + 30-42 days) versus Visit 3 (Day 30-60) | 
| RSV-B serum neutralizing titers expressed as MGI post-Dose 2 over post-Dose 1 | The analysis is performed on the renal and lung SOT patients in the 2-dose group. | At Visit 4 (Visit 3 + 30-42 days) versus Visit 3 (Day 30-60) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RSV-A serum neutralizing titers expressed as Geometric Mean Titers | The analysis is performed on the renal and lung SOT patients and healthy participants. | At Visit 2 in a subset of participants (7-14 days post-dose 1), Visit 3 (30-60 days post dose-1), Visit 4 (Visit 3+30-42 days), Visit 5 (180-210 days post last-dose) and at Visit 6 (350-380 days post last dose) | 
| RSV-B serum neutralizing titers expressed as Geometric Mean Titers | The analysis is performed on the renal and lung SOT patients and healthy participants. | At Visit 2 in a subset of participants (7-14 days post-dose 1), Visit 3 (30-60 days post dose-1), Visit 4 (Visit 3+30-42 days), Visit 5 (180-210 days post last-dose) and at Visit 6 (350-380 days post last dose) | 
| RSV-A serum neutralizing titers expressed as group geometric mean titers (GMT) ratio | Group GMT ratio of RSV_HA group over RSV_IC group (pooled RSV_IC_1 and RSV_IC_2 groups) is assessed at Visit 2 (in a subset of participants) and Visit 3, and RSV_IC_2 over RSV_IC_1, RSV_HA over RSV_IC_1 and RSV_HA over RSV_IC_2 at Visit 4, Visit 5 and Visit 6. | At Day 1 (dose 1), at Visit 2 (7-14 days post-dose 1), Visit 3 (30-60 days post dose-1, dose 2 for the RSV_IC_2 group), Visit 4 (Visit 3+30-42 days), Visit 5 (180-210 days post last-dose) and at Visit 6 (350-380 days post last dose) | 
| RSV-B serum neutralizing titers expressed as group geometric mean titers (GMT) ratio | Group GMT ratio of RSV_HA group over RSV_IC group (pooled RSV_IC_1 and RSV_IC_2 groups) is assessed at Visit 2 (in a subset of participants) and Visit 3, and RSV_IC_2 over RSV_IC_1, RSV_HA over RSV_IC_1 and RSV_HA over RSV_IC_2 at Visit 4, Visit 5 and Visit 6. | At Day 1 (dose 1), at Visit 2 (7-14 days post-dose 1), Visit 3 (30-60 days post dose-1, dose 2 for the RSV_IC_2 group), Visit 4 (Visit 3+30-42 days), Visit 5 (180-210 days post last-dose) and at Visit 6 (350-380 days post last dose) | 
| RSV-A serum neutralizing titers expressed as mean geometric increase (MGI) | MGI is assessed at Visit 2 (in a subset of participants) over Visit 1 and Visit 3 over Visit 1 in RSV_HA and RSV_IC (pooled RSV_IC_1 and RSV_IC_2 groups), and at Visit 4, Visit 5 and Visit 6 over Visit 1 in RSV_IC_1, RSV_2, RSV_HA groups. | At Day 1 (dose 1), at Visit 2 (7-14 days post-dose 1), Visit 3 (30-60 days post dose-1, dose 2 for the RSV_IC_2 group), Visit 4 (Visit 3+30-42 days), Visit 5 (180-210 days post last-dose) and at Visit 6 (350-380 days post last dose) | 
| RSV-B serum neutralizing titers expressed as mean geometric increase (MGI) | MGI is assessed at Visit 2 (in a subset of participants) over Visit 1 and Visit 3 over Visit 1 in RSV_HA and RSV_IC (pooled RSV_IC_1 and RSV_IC_2 groups), and at Visit 4, Visit 5 and Visit 6 over Visit 1 in RSV_IC_1, RSV_2, RSV_HA groups. | At Day 1 (dose 1), at Visit 2 (7-14 days post-dose 1), Visit 3 (30-60 days post dose-1, dose 2 for the RSV_IC_2 group), Visit 4 (Visit 3+30-42 days), Visit 5 (180-210 days post last-dose) and at Visit 6 (350-380 days post last dose) | 
| Cell Mediated Immunity (CMI) response in a subset of participants | CMI response is expressed as group geometric mean of the frequency of RSVPreF3-specific CD4+ and/or CD8+ T cells expressing at least 2 activation markers including at least one cytokine among CD40L, 4-1BB, IL-2, TNF-α, IFN-γ, IL- 13 and IL-17. The CMI is measured in a subgroup consisting of participants with renal and lung SOT (from 1-dose group and 2-dose group) and healthy participants. | At Day 1 (dose 1), at Visit 2 (7-14 days post-dose 1), Visit 3 (30-60 days post dose-1, dose 2 for the RSV_IC_2 group), Visit 4 (Visit 3+30-42 days), Visit 5 (180-210 days post last-dose) and at Visit 6 (350-380 days post last dose) | 
| Percentage of participants with solicited administration site events | Assessed solicited administration site events included pain, redness and swelling, at the injection site. | Within 7 days post-study intervention administration (i.e., the day of vaccination and 6 subsequent days, vaccine administered on Day 1 for all groups and Day 30-60 for RSV_IC_2) | 
| Percentage of participants with solicited systemic events | Assessed solicited systemic events included fever, myalgia, arthralgia, headache, and fatigue. | Within 7 days post-study intervention administration (i.e., the day of vaccination and 6 subsequent days, vaccine administered on Day 1 for all groups and Day 30-60 for RSV_IC_2) | 
| Percentage of participants with unsolicited adverse events (AEs) | An unsolicited AE is an AE that was not included in the list of solicited events. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited AE. | Within 30 days post-study intervention administration (i.e., the day of vaccination and 29 subsequent days, vaccine administered on Day 1 for all groups and Day 30-60 for RSV_IC_2) | 
| Percentage of participants with any serious adverse events (SAEs) after study intervention, SAEs related to study intervention and fatal SAEs | A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study participant. | From Day 1 up to study end (Day 350-380 post last dose, vaccine administered on Day 1 for all groups and Day 30-60 for RSV_IC_2) | 
| Percentage of participants with any potential immune-mediated disease (pIMDs) after study intervention and pIMDs related to study intervention | Potential immune-mediated diseases (pIMDs) are a subset of AEs of special interest (AESIs) that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. | From Day 1 up to study end (Day 350-380 post last dose, vaccine administered on Day 1 for all groups and Day 30-60 for RSV_IC_2) | 
| Percentage of participants with any AESIs | AESIs are AEs of special interest. Along with pIMDs, they include also the acute rejection (specific to renal and lung SOT patients) and Atrial fibrillation (AF). | From Day 1 up to study end (Day 350-380 post last dose, vaccine administered on Day 1 for all groups and Day 30-60 for RSV_IC_2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory syncytial virus, Vaccine, Immunogenicity, Safety