A Study to Learn About Two or More Vaccines That Are Put Together as One Shot Against Infectious Lung Illnesses, Including COVID-19 and Respiratory Syncytial Virus (RSV).

Study Overview
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Brief Summary
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The purpose of the study is tolearn about the safety and effects of a combined vaccine for RSV and COVID-19 when given with a seasonal flu vaccine or when given alone. A combined vaccine will help to reduce the number of vaccinations given when trying to prevent respiratory infections. This study is seeking participants who: are 65 years of age or older. are healthy or have well-controlled chronic conditions. in the past have received at least 3 US-authorized mRNA COVID 19 vaccines, with the most recent vaccine being an updated booster vaccine given at least more than or equal to 150 days before Visit A101 (Day 1). have not had a flu shot in the last 120 days. agree to be present for all study visits, procedures, and blood draws. Participants will be involved in this study for 6 months. During this time, participants will have 2 study visits at the study clinic and a 6-month telephone contact.

Official Title
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A STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF COMBINED VACCINE CANDIDATE(S) AGAINST INFECTIOUS RESPIRATORY ILLNESSES, INCLUDING COVID-19 AND RSV, IN HEALTHY INDIVIDUALS

Conditions
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Healthy Participants

Intervention / Treatment
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* Biological: Combination [RSVpreF+BNTb162b2]
* Biological: Bivalent BNT162b2 (original/Omi BA.4/BA.5)
* Biological: RSVpreF
* Biological: QIV
* Biological: Normal Saline Placebo


Participation Criteria
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Eligibility Criteria
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Substudy A Inclusion Criteria: Male or female participants ≥65 years of age at Visit 1 (Day 1). Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures. Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study. Capable of giving signed informed consent as described in the protocol, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. Participants who have received at least 3 prior US authorized mRNA COVID 19 vaccines, with the last dose being an updated (bivalent) vaccine given at least ≥150 days before Visit A101 (Day 1). Substudy A Exclusion Criteria: A confirmed diagnosis of COVID 19, RSV infection, or influenza ≤120 days before study intervention administration. History of severe adverse reaction associated with any vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s). Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection. Allergy to egg proteins (egg or egg products) or chicken proteins. Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Receipt of chronic systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days before enrollment through conclusion of the study. Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or planned receipt throughout the study. Receipt of any RSV vaccine at any time prior to enrollment, or planned receipt throughout the study. Receipt of any influenza vaccine ≤120 days before study enrollment. Participation in other studies involving a study intervention within 28 days before randomization. Anticipated participation in other studies within 28 days after receipt of study intervention in this study. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Combination [RSVpreF+BNT162b2] + Quadrivalent influenza vaccine (QIV) | Biological: Combination [RSVpreF+BNTb162b2]<br>* Combination of RSVpreF and Bivalent BNT162b2 given as a single intramuscular injection<br>Biological: QIV<br>* Licensed QIV given as an intramuscular injection<br>|
| Experimental: Group 2<br>Combination [RSVpreF+BNT162b2] + placebo | Biological: Combination [RSVpreF+BNTb162b2]<br>* Combination of RSVpreF and Bivalent BNT162b2 given as a single intramuscular injection<br>Biological: Normal Saline Placebo<br>* Normal saline (0.9% sodium chloride solution for injection)<br>|
| Active Comparator: Group 3<br>BNT162b2 + placebo | Biological: Bivalent BNT162b2 (original/Omi BA.4/BA.5)<br>* Bivalent BNT162b2 given as an intramuscular injection<br>Biological: Normal Saline Placebo<br>* Normal saline (0.9% sodium chloride solution for injection)<br>|
| Active Comparator: Group 4<br>RSVpreF + placebo | Biological: RSVpreF<br>* RSVpreF given as an intramuscular injection<br>Biological: Normal Saline Placebo<br>* Normal saline (0.9% sodium chloride solution for injection)<br>|
| Active Comparator: Group 5<br>QIV + placebo | Biological: QIV<br>* Licensed QIV given as an intramuscular injection<br>Biological: Normal Saline Placebo<br>* Normal saline (0.9% sodium chloride solution for injection)<br>|
| Experimental: Group 6<br>Coadministration RSVpreF + bivalent BNT162b2 + placebo | Biological: Bivalent BNT162b2 (original/Omi BA.4/BA.5)<br>* Bivalent BNT162b2 given as an intramuscular injection<br>Biological: RSVpreF<br>* RSVpreF given as an intramuscular injection<br>Biological: Normal Saline Placebo<br>* Normal saline (0.9% sodium chloride solution for injection)<br>|
| Experimental: Group 7<br>Coadministration RSVpreF + bivalent BNT162b2 + QIV | Biological: Bivalent BNT162b2 (original/Omi BA.4/BA.5)<br>* Bivalent BNT162b2 given as an intramuscular injection<br>Biological: RSVpreF<br>* RSVpreF given as an intramuscular injection<br>Biological: QIV<br>* Licensed QIV given as an intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants reporting local reactions | Pain at the injection site, redness, and swelling | For up to 7 days following vaccination (Day 7) | 
| Percentage of participants reporting systemic events | Fever, fatigue, headache, vomiting, diarrhea, chills, new or worsened muscle pain, and new or worsened joint pain | For up to 7 days following vaccination (Day 7) | 
| Percentage of participants reporting adverse events | As elicited by investigational site staff | Within 1 month following vaccination (Day 28) | 
| Percentage of participants reporting serious adverse events | As elicited by investigational site staff | Within 6 months following vaccination (Day 175) | 
| Group 1 vs Group 4 noninferiority analysis: Geometric mean ratios (GMRs) of RSV A and RSV B neutralizing titers (NTs) | As measured at central laboratory. | 1 month after vaccination (Day 28) | 
| Group 1 vs Group 3 noninferiority analysis: Geometric mean ratios (GMRs) of SARS-CoV-2 Omicron BA.4/BA.5-strain neutralizing titers (NTs) | As measured at central laboratory. | 1 month after vaccination (Day 28) | 
| Group 1 vs Group 3 noninferiority analysis: Geometric mean ratios (GMRs) of SARS-CoV-2 reference-strain neutralizing titers (NTs) | As measured at central laboratory. | 1 month after vaccination (Day 28) | 
| Group 1 vs Group 5 noninferiority analysis: Influenza strain-specific geometric mean ratios (GMRs) of hemagglutination inhibition (HAI) titers. | As measured at central laboratory. | 1 month after vaccination (Day 28) | 
| Group 2 vs Group 4 noninferiority analysis: Geometric mean ratios (GMRs) of RSV A and RSV B neutralizing titers (NTs) | As measured at central laboratory. | 1 month after vaccination (Day 28) | 
| Group 2 vs Group 3 noninferiority analysis: Geometric mean ratios (GMRs) of SARS-CoV-2 Omicron BA.4/BA.5-strain neutralizing titers (NTs) | As measured at central laboratory. | 1 month after vaccination (Day 28) | 
| Group 2 vs Group 3 noninferiority analysis: Geometric mean ratios (GMRs) of SARS-CoV-2 reference-strain neutralizing titers NTs | As measured at central laboratory. | 1 month after vaccination (Day 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Group 7 vs Group 4 noninferiority analysis: Geometric mean ratios (GMRs) of RSV A and RSV B neutralizing titers (NTs) | As measured at central laboratory | 1 month after vaccination (Day 28) | 
| Group 7 vs Group 3 noninferiority analysis: Geometric mean ratios (GMRs) of SARS-CoV-2 Omicron BA.4/BA.5-strain neutralizing titers (NTs) | As measured at central laboratory | 1 month after vaccination (Day 28) | 
| Group 7 vs Group 3 noninferiority analysis: Geometric mean ratios (GMRs) of SARS-CoV-2 reference-strain neutralizing titers (NTs) | As measured at central laboratory | 1 month after vaccination (Day 28) | 
| Group 7 vs Group 5 noninferiority analysis: Influenza strain-specific geometric mean ratio (GMR) of hemagglutination inhibition (HAI) titers. | As measured at central laboratory | 1 month after vaccination (Day 28) | 
| Group 6 vs Group 4 noninferiority analysis: Geometric mean ratios (GMRs) of RSV A and RSV B neutralizing titers (NTs) | As measured at central laboratory | 1 month after vaccination (Day 28) | 
| Group 6 vs Group 3 noninferiority analysis: Geometric mean ratios (GMRs) of SARS-CoV-2 Omicron BA.4/BA.5-strain neutralizing titers (NTs) | As measured at central laboratory | 1 month after vaccination (Day 28) | 
| Group 6 vs Group 3 noninferiority analysis: Geometric mean ratios (GMRs) of SARS-CoV-2 reference-strain neutralizing titers (NTs) | As measured at central laboratory | 1 month after vaccination (Day 28) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Vaccine, RSV, Respiratory Syncytial Virus, mRNA vaccine, Flu, SARS-CoV-2, COVID-19, Combination vaccine