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 60 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 seasonal quadrivalent influenza vaccine (FLU-QIV) in adults aged 60 years and above compared to separate administration of the vaccines.

Official Title
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A Phase 3, Open-label, Randomized, Controlled, Multi-country Study to Evaluate the Immune Response, Safety and Reactogenicity of RSVPreF3 OA Investigational Vaccine When Co-administered With FLU-QIV Vaccine in Adults Aged 60 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-QIV


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 ≥60 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 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. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. Hypersensitivity to latex. History of GBS, anaphylaxis, febrile seizures, Bell's palsy and narcolepsy. 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 dose of study vaccines and ending 30 days after the last vaccine administration, or planned use during the study period. Administration of an influenza vaccine during the 6 months preceding the study FLU-QIV 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 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: 60 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 received 1 dose of RSV_PreF3 Older Adult (OA) investigational vaccine and 1 dose of FLU-QIV at Day 1 and were 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-QIV<br>* FLU-QIV administered intramuscularly in the deltoid region of the dominant (Co-Ad Group) arm or the non-dominant (Control Group) arm.<br>|
| Active Comparator: Control Group<br>Participants received 1 dose of FLU-QIV at Day 1 and 1 dose of RSV_PreF3 OA investigational vaccine at Day 31 and were 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-QIV<br>* FLU-QIV administered intramuscularly in the deltoid region of the dominant (Co-Ad Group) arm or the non-dominant (Control Group) arm.<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 Geometric Mean Titers (GMTs) | The serum neutralization assay is a functional assay that measures the ability of serum antibodies to neutralize RSV-A entry and replication in a host cell line. The serum neutralizing antibody titer is expressed in ED60 (Estimated Dilution 60) and corresponds to the inverse of the interpolated serum dilution that yields a 60% reduction of the signal compared to a control without serum. | At 1 month after the RSV_PreF3 OA investigational vaccine dose (at Day 31 for the Co-Ad Group and at Day 61 for the Control Group) | 
| Hemagglutinin Inhibition (HI) Antibody Titers for Each of the FLU Vaccine Strains Expressed as Group GMTs | HI antibody titers were assessed for each of the Flu vaccine strains, namely Flu A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria). The serum HI antibody titers are expressed in 1/Dilution (DIL) where DIL corresponds to the highest dilution that shows complete HI. | 1 month after the FLU vaccine dose (at Day 31) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary: HI Seroconversion Status for Each of the Flu Vaccine Strains Expressed as Seroconversion Rate (SCR) | SCR for HI antibody response was defined as the percentage of vaccinees who have either a HI pre-dose titer < 1:10 and a post-dose titer >= 1:40 or a pre-dose titer >= 1:10 and at least a four-fold increase in post-dose titer. HI antibody titers were assessed for each of the Flu vaccine strains, namely Flu A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria). | 1 month after the FLU vaccine dose (at Day 31) | 
| RSV-A Neutralization Antibody Titers Expressed as Mean Geometric Increase (MGI) | MGI was defined as the geometric mean of the within participant ratios of the post dose titer over the pre-dose titer. | 1 month after the RSV_PreF3 OA investigational vaccine dose (at Day 31 for the Co-Ad Group and at Day 61 for the Control Group) | 
| RSV-B Neutralization Antibody Titers Expressed as Geometric Mean Titers (GMT) | The serum neutralization assay is a functional assay that measures the ability of serum antibodies to neutralize RSV-B entry and replication in a host cell line. The serum neutralizing antibody titer is expressed in ED60 (Estimated Dilution 60) and corresponds to the inverse of the interpolated serum dilution that yields a 60% reduction of the signal compared to a control without serum. | 1 month after the RSV_PreF3 OA investigational vaccine dose (at Day 31 for the Co-Ad Group and at Day 61 for the Control Group) | 
| RSV-B Neutralization Antibody Titers Expressed as MGI | MGI was defined as the geometric mean of the within participant ratios of the post-dose titer over the pre-dose titer. | 1 month after the RSV_PreF3 OA investigational vaccine dose (at Day 31 for the Co-Ad Group and at Day 61 for the Control Group) | 
| HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | HI antibody titers were assessed for each of the Flu vaccine strains, namely A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria). The serum HI antibody titers are expressed in 1/DIL where DIL corresponds to the highest dilution that shows complete HI. | At baseline (at Day 1) and 1 month after the FLU vaccine dose (at Day 31) | 
| HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | SPR for HI antibody response was defined as percentage of vaccinees with a serum HI titer >= 1:40 that usually is accepted as indicating protection. HI antibody titers were assessed for each of the Flu vaccine strains, namely A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria). | At baseline (at Day 1) and 1 month after the FLU vaccine dose (at Day 31) | 
| HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as MGI | MGI was defined as the geometric mean of the within participant ratios of the post-dose titer over the pre-dose titer. HI antibody were assessed for each of the FLUvaccine strain, namely A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria). | 1 month after the FLU vaccine dose (at Day 31) | 
| Percentage of Participants With Solicited Administration Site Events | Solicited administration site adverse events(AEs) assessed were erythema, pain and swelling. Any = occurrence of the adverse event regardless of intensity grade. | Within 4 days (the day of vaccination and 3 subsequent days) after each vaccination | 
| Percentage of Participants With Solicited Systemic Events | Solicited systemic events assessed were arthralgia, fatigue, fever [defined as temperature equal to or above (>=) 38 degrees Celsius (C)/100.4 degrees Fahrenheit (F)], headache and myalgia. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination. | Within 4 days (the day of vaccination and 3 subsequent days) after each vaccination | 
| Percentage of Participants Reporting at Least One Unsolicited Adverse Event | An unsolicited AEs is any AE reported in addition to those solicited during the clinical study and that was not included in a list of solicited events using a Participant Diary. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event. Unsolicited AEs include serious, non-serious AEs and potential immune-mediated diseases (pIMDs). Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. | Within 30 days (the day of vaccination and 29 subsequent days) after each vaccination | 
| Percentage of Participants Reporting at Least One Serious Adverse Event (SAE) | An 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. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination. | From Day 1 up to study end (6 months after last vaccination) | 
| Percentage of Participants Reporting at Least One Potential Immune-mediated Disease (pIMD) | 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. | From Day 1 up to study end (6 months after last vaccination) |