A Study on the Immune Response and Safety Elicited by a Vaccine Against Respiratory Syncytial Virus (RSV) When Given Alone and Together With a Vaccine Against Influenza in Adults Aged 65 Years and Above

Study Overview
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Brief Summary
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The purpose of this study is to assess the immunogenicity, safety and reactogenicity of the RSVPreF3 OA investigational vaccine when co-administered with the high dose quadrivalent influenza (FLU HD) vaccine in adults aged 65 years and above compared to separate administration of the vaccines.

Official Title
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A Phase 3, Open-label, Randomized, Controlled, Multicountry Study to Evaluate the Immune Response, Safety and Reactogenicity of RSVPreF3 OA Investigational Vaccine When Co-administered With FLU HD Vaccine 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 HD 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 A male or female ≥65 years of age 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 vaccination. Participants with chronic stable medical conditions with or without specific treatment 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 vaccines. Hypersensitivity to latex. History of Guillain Barré syndrome, or anaphylaxis. Serious or unstable chronic illness. Any history of dementia or any medical condition that moderately or severely impairs cognition. 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 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 study vaccine administration, 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. Note: In case an emergency mass vaccination for an unforeseen public health threat (e.g.: a pandemic) is recommended and/or organized by the public health authorities, outside the routine immunization program, the time period described above can be reduced if necessary for that vaccine provided it is used according to the local governmental recommendations and that the Sponsor is notified accordingly. 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 first dose of study vaccine 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 vaccination 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 intervention (drug/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. Planned move during the study conduct that prohibits participation until 1 month post-last vaccine administration. Bedridden participants. 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 HD at Day 1 and are followed up until the study end. | Biological: RSVPreF3 OA investigational vaccine<br>* RSVPreF3 OA investigational vaccine administered intramuscularly in the deltoid region of the non-dominant arm.<br>Biological: FLU HD vaccine<br>* FLU HD vaccine administered intramuscularly in the deltoid region of the dominant arm (Co-Ad Group) or the non-dominant arm (Control Group).<br>|
| Active Comparator: Control Group<br>Participants randomized to Control Group receive 1 dose of FLU HD at Day 1, followed by 1 dose of RSVPreF3 OA investigational vaccine at Day 31 and are followed up until the study end. | Biological: RSVPreF3 OA investigational vaccine<br>* RSVPreF3 OA investigational vaccine administered intramuscularly in the deltoid region of the non-dominant arm.<br>Biological: FLU HD vaccine<br>* FLU HD vaccine administered intramuscularly in the deltoid region of the dominant arm (Co-Ad Group) or the non-dominant arm (Control Group).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RSV-A neutralization antibody titers expressed as group geometric mean titer (GMT) ratio |  | 1 month after the RSVPreF3 OA investigational vaccine dose | 
| Hemagglutinin inhibition (HI) antibody titers for each of the FLU vaccine strains, expressed as group GMT ratio |  | 1 month after the FLU vaccine dose | 
| RSV-B neutralization antibody titers expressed as group GMT ratio |  | 1 month after the RSVPreF3 OA investigational vaccine dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HI seroconversion rate (SCR) for each of the FLU vaccine strains | The HI SCR was measured to evaluate the non-inferiority of FLU vaccine when co-administered with the RSVPreF3 OA investigational vaccine, compared to FLU vaccine administered alone, and to evaluate the humoral immune response to the FLU vaccine when co-administered with the RSVPreF3 OA investigational vaccine or administered alone. | 1 month after the FLU vaccine dose | 
| RSV-A neutralization antibody titers expressed as mean geometric increase (MGI) |  | 1 month after the RSVPreF3 OA investigational vaccine dose | 
| RSV-B neutralization antibody titers expressed as MGI |  | 1 month after the RSVPreF3 OA investigational vaccine dose | 
| HI antibody titers for each of the FLU vaccine strains, expressed as GMT |  | At Day 1 and 1 month after vaccination (Day 31) | 
| HI seroprotection rate (SPR) for each of the FLU vaccine strains |  | At Day 1 and 1 month after vaccination (Day 31) | 
| HI antibody titers for each of the FLU vaccine strains, expressed as MGI |  | 1 month after the FLU vaccine dose | 
| Percentage of participants with solicited administration site events | The solicited administration site events after vaccination include pain, erythema/redness and swelling. | Within 4 days (the day of vaccination and 3 subsequent days) after each vaccination (administered on Day 1 and 31) | 
| Percentage of participants with solicited systemic events | The solicited systemic events after vaccination include fever, headache, fatigue, myalgia and arthralgia. | Within 4 days (the day of vaccination and 3 subsequent days) after each vaccination (administered on Day 1 and 31) | 
| Percentage of participants with unsolicited adverse events (AEs) (potential immune-mediated disease (pIMD), non-serious AE or serious AE) | An unsolicited AEs is an AE that was not included in a list of solicited events using a Participant Diary. Unsolicited events must have been spontaneously communicated by a participant who has signed the informed consent. Unsolicited AEs include both serious, non-serious AEs and pIMDs. | Within 30 days (the day of vaccination and 29 subsequent days) after each vaccination | 
| Percentage of participants with serious adverse events (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, is a congenital anomaly/birth defect in the offspring of a study participant. | From Day 1 up to study end (6 months after last vaccination) | 
| Percentage of participants with 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 up to study end (6 months after last vaccination) | 

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