A Study on the Immune Response and Safety of a Vaccine Against Respiratory Syncytial Virus (RSV) When Given Alone or Co-administered With an Adjuvanted Vaccine Against Influenza in Adults Aged 65 Years and Above

Study Overview
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Brief Summary
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The aim of this study is to assess the immunogenicity, safety and reactogenicity of the RSV PreFusion protein 3 older adult (RSVPreF3 OA) investigational vaccine when co-administered with an adjuvanted quadrivalent influenza (FLU aQIV) vaccine, in adults aged 65 years of age (YOA).

Official Title
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A Phase III, Open-label, Randomized, Controlled, Multi-country Study to Evaluate the Immune Response, Safety and Reactogenicity of an RSVPreF3 OA Investigational Vaccine When Co-administered With FLU aQIV (Inactivated Influenza Vaccine - Adjuvanted) in Adults Aged 65 Years and Above

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Biological: RSVPreF3 OA investigational vaccine
* Biological: FLU vaccine


Participation Criteria
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Eligibility Criteria
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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 electronic diary cards [eDiaries], return for follow-up visits, ability to access and utilize a phone or other electronic communications). A male or female ≥ 65 YOA at the time of the first study intervention administration. 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. 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 the time of first study intervention administration. 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. Exclusion Criteria: Medical conditions Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy, 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 interventions, in particular any history of severe allergic reaction to egg protein or to a previous influenza vaccine. Hypersensitivity to latex. Guillain-Barré syndrome that occurred within 6 weeks of receipt of prior influenza vaccine. Serious or unstable chronic illness. Any history of dementia or any medical condition that moderately or severely impairs cognition. Recurrent 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. Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study. Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. Prior/Concomitant therapy Use of any investigational or non-registered product (drug, vaccine, or medical device) other than the study interventions during the period beginning 30 days before the first dose of study interventions, or planned use during the study period. Administration of an influenza vaccine during the 6 months preceding the study FLU vaccine administration. Planned or actual administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first study intervention administration and ending 30 days after the last study intervention administration. In the case of COVID-19 vaccines, this time window can be decreased to 14 days before and after each study intervention administration provided this COVID-19 vaccine use is in line with local governmental recommendations. Previous vaccination with an RSV vaccine. Administration of long-acting immune-modifying drugs or planned administration at any time during the study period. Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the administration of first dose of study interventions or planned administration during the study period. Chronic administration (defined as more than 14 consecutive days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the first study intervention dose or planned administration during the study period. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed. Prior/Concurrent clinical study experience • 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 vaccine/product (drug or invasive medical device). Other exclusions 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. Bedridden participants. Planned move during the study conduct that prohibits participation until study end. Participation of any study personnel or their immediate dependents, family, or household members.

Ages Eligible for Study
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Minimum Age: 65 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: Co-Ad Group<br>Participants randomized to Co-Ad Group receive 1 dose of RSVPreF3 OA investigational vaccine and 1 dose of FLU aQIV vaccine (Flu vaccine) at Day 1. | Biological: RSVPreF3 OA investigational vaccine<br>* One dose of RSVPreF3 OA investigational vaccine administered intramuscularly.<br>Biological: FLU vaccine<br>* One dose of FLU vaccine administered intramuscularly.<br>* Other names: Fluad Tetra, FLUAD QUADRIVALENT, Fluad Quad;|
| Active Comparator: Control Group<br>Participants randomized to Control Group receive 1 dose of FLU vaccine at Day 1, followed by 1 dose of RSVPreF3 OA investigational vaccine at Day 31. | Biological: RSVPreF3 OA investigational vaccine<br>* One dose of RSVPreF3 OA investigational vaccine administered intramuscularly.<br>Biological: FLU vaccine<br>* One dose of FLU vaccine administered intramuscularly.<br>* Other names: Fluad Tetra, FLUAD QUADRIVALENT, Fluad Quad;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemagglutination inhibition (HI) antibody titers for each of the FLU vaccine strains, expressed as group geometric mean titer (GMT) ratio |  | At 1 month after the FLU vaccine dose (Day 31 for both groups) | 
| RSV-A neutralization antibody titers expressed as group GMT ratio |  | At 1 month after the RSVPreF3 OA investigational vaccine dose (Day 31 for the CoAd Group and Day 61 for the Control Group) | 
| RSV-B neutralization antibody titers expressed as group GMT ratio |  | At 1 month after the RSVPreF3 OA investigational vaccine dose (Day 31 for the Co Ad Group and Day 61 for the Control Group) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HI seroconversion rate (SCR) for each of the FLU vaccine strains | HI SCR is defined as the percentage of participants who have either a HI predose titer less than (<) 1:10 and a post-dose titer greater than or equal to (≥) 1:40, or a pre-dose titer ≥ 1:10 and at least a 4-fold increase in post-dose titer. | At 1 month after the FLU vaccine dose (Day 31 for both groups) | 
| RSV-A neutralization antibody titers expressed as mean geometric increase (MGI) | MGI is defined as the geometric mean of the within-participant ratios of the post-dose titer over the pre-dose titer. | At 1 month after the RSVPreF3 OA investigational vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group) | 
| RSV-B neutralization antibody titers expressed as group GMT ratio |  | At 1 month after the RSVPreF3 OA investigational vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group) | 
| RSV-B neutralization antibody titers expressed as MGI | MGI is defined as the geometric mean of the within-participant ratios of the post-dose titer over the pre-dose titer. | At 1 month after the RSVPreF3 OA investigational vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group) | 
| HI antibody titers for each of the FLU vaccine strains, expressed as GMT |  | At Day 1 and Day 31 | 
| HI SCR for each of the FLU vaccine strains | HI SCR is defined as the percentage of participants who have either a HI predose titer < 1:10 and a post-dose titer ≥ 1:40 or a pre-dose titer ≥ 1:10 and at least a 4-fold increase in post-dose titer. | From Day 1 to Day 31 | 
| HI seroprotection rate (SPR) for each of the FLU vaccine strains | HI SPR is defined as the percentage of participants with a serum HI titer ≥ 1:40. | At Day 1 and Day 31 | 
| HI antibody titers for each of the FLU vaccine strains, expressed as MGI | MGI is defined as the geometric mean of the within-participant ratios of the post-dose titer over the pre-dose titer. | At 1 month after the FLU vaccine dose (Day 31 for both groups) | 
| Percentage of participants reporting each solicited administration site event | The solicited administration site events after vaccination include pain, erythema/redness and swelling. | Within 7 days (the day of vaccination and 6 subsequent days) after vaccine administration | 
| Percentage of participants reporting each solicited systemic event | The solicited systemic events after vaccination include fever, headache, fatigue, myalgia and arthralgia. | Within 7 days (the day of vaccination and 6 subsequent days) after vaccine administration | 
| Percentage of participants reporting unsolicited adverse events (AEs) | An unsolicited AEs is an AE that is not included in a list of solicited events using a Participant Diary. Unsolicited events must be spontaneously communicated by a participant who signs the informed consent. Unsolicited AEs include both serious, non-serious AEs and potential immune-mediated diseases (pIMDs). | Within 30 days (the day of vaccination and 29 subsequent days) after vaccine administration | 
| Percentage of participants reporting SAEs | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study participant. | From Day 1 until 6 months after last vaccination (Month 6 for the Co-Ad Group, Month 7 for the Control group) | 
| Percentage of participants reporting pIMDs | pIMDs are a subset of AEs of special interest that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. The investigator must exercise his/her medical/scientific judgment to determine whether other diseases have an autoimmune origin (i.e., pathophysiology involving systemic or organ-specific pathogenic autoantibodies) and should also be recorded as a pIMD. | From Day 1 until 6 months after last vaccination (Month 6 for the Co-Ad Group, Month 7 for the Control group) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Reactogenicity, Adults aged 65 years and above, Respiratory syncytial virus, Adjuvanted quadrivalent influenza vaccine, Immunogenicity, Safety