A Study of Various Respiratory Syncytial Virus (RSV) Pre-Fusion (preF)-Based Vaccine Formulations in Adults Aged 60 Years and Older

Study Overview
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Brief Summary
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The purpose of the study is to evaluate safety and immunogenicity of various respiratory syncytial virus (RSV) pre-Fusion (preF)-based vaccine components followed by expanded safety evaluation and durability/revaccination evaluation of the selected RSV preF-based vaccine formulation in participants aged greater than or equal to (>=) 60 years in stable health.

Detailed Description
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RSV is an important cause of serious respiratory infections in adults aged 60 years and older. The current study is divided into four cohorts, evaluating various doses and combinations of RSV preF-based vaccines. Cohort 1 will assess the safety and reactogenicity of different RSV preF-based vaccines. Cohort 2 is an expansion of cohort 1 and will assess both safety and immunogenicity of these different RSV vaccines. based on C1 and 2 data the optimal vaccine composition will be selected and further evaluated in Cohort 3 and 4 including durability and revaccination. Cohort 3 will accumulate safety data on the selected vaccine and optimize its formulation. Cohort 4 is an expansion of several arms in cohort 3, aimed to understand the durability of the immune response induced by the selected vaccine, and to explore the possibility for revaccination.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 1/2a Study for Safety and Immunogenicity Evaluations of Various RSV.preF-based Vaccine Formulations in Adults Aged 60 Years and Older

Conditions
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Respiratory Syncytial Virus-associated Lower Respiratory Tract Disease Prevention

Intervention / Treatment
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* Biological: RSV preF-based Vaccine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In the investigator's clinical judgment, participant must be in stable health at the time of vaccination. Participants may have underlying illnesses such as hypertension, congestive heart failure, chronic obstructive pulmonary disease (COPD), Type 2 diabetes mellitus, hyperlipoproteinemia, or hypothyroidism, as long as their symptoms and signs are stable at the time of vaccination, and these conditions receive routine follow-up by the participant's healthcare provider. Participants will be included on the basis of physical examination, medical history, and vital signs performed between informed consent form (ICF) signature and vaccination For participants in Cohorts 1 and 2 only: Participant must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the laboratory screening tests are outside the laboratory normal reference ranges and additionally within the limits of toxicity Grade 2 according to the United States Food and Drug Administration (US FDA) toxicity tables (that is, for tests in the FDA table), the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant and appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator Agrees not to donate blood from the time of vaccination through 3 months after vaccination Must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study Exclusion Criteria: History of malignancy within 5 years before screening not in the following categories: a) Participants with squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix may be enrolled at the discretion of the investigator; b) Participants with a history of malignancy within 5 years before screening, with minimal risk of recurrence per investigator's judgment, can be enrolled Known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine components Per medical history, participant has chronic active hepatitis B or hepatitis C infection, human immunodeficiency viruses (HIV) type 1 or type 2 infection, acute polyneuropathy (example, Guillain-Barré syndrome) or chronic idiopathic demyelinating polyneuropathy Participant is in receipt of, or planning to receive, licensed live attenuated vaccine within 28 days before and after study vaccinations; other licensed vaccines (that is, not live such as, influenza, tetanus, hepatitis A or B, rabies) within 14 days before and after study vaccinations Received treatment with immunoglobulins expected to impact the vaccine-induced immune response (including monoclonal antibodies [MAbs] for chronic underlying conditions) in the 2 months; immunoglobulins specific to respiratory syncytial virus (RSV), human metapneumovirus, or parainfluenza viruses in the 12 months; apheresis therapies in the 4 months; or blood products in the 4 months prior to study vaccination or has any plans to receive such treatment during the study

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1a: Respiratory Syncytial Virus (RSV) preFusion (preF) Based Vaccine<br>Participants will receive single dose of mixture of RSV preF-based vaccine in cohort (C) 1 (Group [G] 1) and C 2 through intramuscular injection on Day 1. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>|
| Experimental: Arm 1b: RSV preF Based Vaccine<br>Participants will receive single dose of mixture of RSV preF-based vaccine in C 1 (G 1-4) and C 2 through intramuscular injection on Day 1. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>|
| Experimental: Arm 1c: Placebo<br>Participants will receive single dose of placebo in C 1 (G 1-4) and C 2 through intramuscular injection on Day 1. | Drug: Placebo<br>* Placebo will be administered as intramuscular injection.<br>|
| Experimental: Arm 2: RSV preF Based Vaccine<br>Participants will receive single dose of mixture of RSV preF-based vaccine in C 1 (G 2) and C 2 through intramuscular injection on Day 1. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>|
| Experimental: Arm 3: RSV preF Based Vaccine<br>Participants will receive single dose of mixture of RSV preF-based vaccine in C 1 (G 2) and C 2 through intramuscular injection on Day 1. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>|
| Experimental: Arm 4: RSV preF Based Vaccine<br>Participants will receive single dose of mixture of RSV preF-based vaccine in C 1 (G 2) and C 2 through intramuscular injection on Day 1. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>|
| Experimental: Arm 5: RSV preF Based Vaccine<br>Participants will receive single dose of mixture of RSV preF-based vaccine in C 1 (G 2) and C 2 through intramuscular injection on Day 1. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>|
| Experimental: Arm 6: RSV preF Based Vaccine<br>Participants will receive single dose of mixture of RSV preF-based vaccine in C 1 (G 2) and C 2 through intramuscular injection on Day 1. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>|
| Experimental: Arm 7: RSV preF Based Vaccine<br>Participants will receive single dose of mixture of RSV preF-based vaccine in C 1 (G 3) and C 2 through intramuscular injection on Day 1. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>|
| Experimental: Arm 8: RSV preF Based Vaccine<br>Participants will receive single dose of mixture of RSV preF-based vaccine in C 1 (G 3) and C 2 through intramuscular injection on Day 1. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>|
| Experimental: Arm 9: RSV preF Based Vaccine<br>Participants will receive single dose of mixture of RSV preF-based vaccine in C 1 (G 4) and C 2 through intramuscular injection on Day 1. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>|
| Experimental: Arm 10: RSV preF Based Vaccine<br>Participants will receive a single dose of selected formulation (based on C 1 and 2 results) in C 3 through intramuscular injection on Day 1. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>|
| Experimental: Arm 11a: RSV preF Based Vaccine and Placebo<br>Participants in C 3 will receive a single dose of first vaccination with selected formulation (as per data C1 and 2) plus placebo on Day 1 and re-vaccination with selected formulation whenever revaccination would be needed through intramuscular injection. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>Drug: Placebo<br>* Placebo will be administered as intramuscular injection.<br>|
| Experimental: Arm 11b: RSV preF Based Vaccine and Placebo<br>Participants in C 3 will receive a single dose of first vaccination with selected formulation (as per data from C 1 and 2) plus placebo on Day 1 and re-vaccination with placebo whenever revaccination would be needed through intramuscular injection. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>Drug: Placebo<br>* Placebo will be administered as intramuscular injection.<br>|
| Experimental: Arm 12: RSV preF Based Vaccine and Placebo<br>Participants in C 3 will receive first vaccination with placebo on Day 1 and re-vaccination with selected formulation (as per data from C 1 and 2) whenever revaccination would be needed through intramuscular injection. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>Drug: Placebo<br>* Placebo will be administered as intramuscular injection.<br>|
| Experimental: Arm 13: RSV preF Based Vaccine<br>Participants in C 3 will receive the mixture of RSV preF-based vaccine plus placebo on Day 1 through intramuscular injection. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>Drug: Placebo<br>* Placebo will be administered as intramuscular injection.<br>|
| Experimental: Arm 14: RSV preF Based Vaccine<br>Participants in C 4 will receive first vaccination with selected formulation (as per data from C 1 and 2) on Day 1 and re-vaccination with selected formulation whenever revaccination would be needed through intramuscular injection. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>|
| Experimental: Arm 15: RSV preF Based Vaccine and Placebo<br>Participants in C 4 will receive first vaccination with selected formulation (as per data from C 1 and 2) on Day 1 and re-vaccination with placebo whenever revaccination would be needed through intramuscular injection. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>Drug: Placebo<br>* Placebo will be administered as intramuscular injection.<br>|
| Experimental: Arm 16: RSV preF Based Vaccine and Placebo<br>Participants in C 4 will receive first vaccination with placebo on Day 1 and re-vaccination with selected formulation (as per data from C 1 and 2) whenever revaccination would be needed through intramuscular injection. | Biological: RSV preF-based Vaccine<br>* RSV preF-based vaccine will be administered as intramuscular injection.<br>Drug: Placebo<br>* Placebo will be administered as intramuscular injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohorts 1, 2 and 3 (Arms 10 and 13): Number of Participants With Serious Adverse Events (SAEs) | An SAE is an adverse event (AE) resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. | Up to 6 months after vaccination (Up to Day 181) | 
| Cohort 3 (Arms 11a, 11b and 12): Number of Participants With SAEs | An SAE is an adverse event (AE) resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. | Up to 6 months after re-vaccination | 
| Cohort 1s, 2 and 3 (Arms 10 and 13): Percentage of Participants with Adverse Event of Special Interest (AESI) | Percentage of participants with AESI will be reported | Up to 6 months after vaccination (Up to Day 181) | 
| Cohort 3 (Arms 11a, 11b and 12): Percentage of participants with AESI | Percentage of participants with AESI will be reported | Up to 6 months after re-vaccination | 
| Cohorts 1, 2 and 3 (Arms 10 and 13): Percentage of Participants With Solicited Local Adverse Events (AEs) | Number of participants with solicited local AEs will be reported. Solicited local AE's include pain/tenderness, erythema, and induration/swelling. | Up to 7 days after vaccination (Up to Day 8) | 
| Cohort 3 (Arms 11a, 11b and 12): Percentage of Participants With Solicited Local AEs | Number of participants with solicited local AEs will be reported. Solicited local AE's include pain/tenderness, erythema, and induration/swelling. | Up to 7 days after vaccination on Day 1 (Up to Day 8) | 
| Cohort 3 (Arms 11a, 11b and 12): Percentage of Participants With Solicited Local AEs | Number of participants with solicited local AEs will be reported. Solicited local AE's include pain/tenderness, erythema, and induration/swelling. | Up to 7 days after re-vaccination | 
| Cohorts 1, 2 and 3 (Arms 10 and 13): Percentage of Participants with Solicited Systemic AEs | Number of participants with solicited systemic AEs will be reported. Solicited systemic AEs include headache, fatigue, myalgia, arthralgia, chills, and fever. | Up to 7 days after vaccination (Up to Day 8) | 
| Cohort 3 (Arms 11a, 11b and 12): Percentage of Participants with Solicited Systemic AEs | Number of participants with solicited systemic AEs will be reported. Solicited systemic AEs include headache, fatigue, myalgia, arthralgia, chills, and fever. | Up to 7 days after vaccination on Day 1 (Up to Day 8) | 
| Cohort 3 (Arms 11a, 11b and 12): Percentage of Participants with Solicited Systemic AEs | Number of participants with solicited systemic AEs will be reported. Solicited systemic AEs include headache, fatigue, myalgia, arthralgia, chills, and fever. | Up to 7 days after re-vaccination) | 
| Cohorts 1, 2 and 3 (Arms 10 and 13): Percentage of Participants With Unsolicited AEs | Number of participants with unsolicited AEs will be reported. Unsolicited AEs include all AEs for which the participant is not specifically questioned in the participant diary. | Up to 28 days after vaccination (Up to Day 29) | 
| Cohort 3 (Arms 11a, 11b and 12): Percentage of Participants with Unsolicited AEs | Number of participants with unsolicited AEs will be reported. Unsolicited AEs include all AEs for which the participant is not specifically questioned in the participant diary. | Up to 28 days after vaccination on Day 1 (Up to Day 29) | 
| Cohort 3 (Arms 11a, 11b and 12): Percentage of Participants with Unsolicited AEs | Number of participants with unsolicited AEs will be reported. Unsolicited AEs include all AEs for which the participant is not specifically questioned in the participant diary. | Up to 28 days after re-vaccination | 
| Cohorts 2 and 4: Respiratory Syncytial Virus (RSV) Neutralizing Antibody Levels | RSV Neutralizing Antibody Levels will be reported | Up to Day 1095 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 2: RSV Fusion Protein (F Protein) Binding Antibodies as Assessed by Enzyme-Linked Immunosorbent assay (ELISA) | Antibodies binding to RSV F protein in pre-fusion (pre-F) and/or post-fusion (post-F) form will be assessed by ELISA. | Up to Day 1095 | 
| Cohort 2: Interferon Gamma (IFN-gamma) Enzyme-Linked Immunospot (ELISpot) Assay | IFN-gamma ELISpot assay will be performed to assess T-cell IFN-gamma responses to RSV F protein peptides. | Up to Day 1095 | 
| Cohort 3: Respiratory Syncytial Virus (RSV) Neutralizing Antibody Levels | RSV Neutralizing Antibody Levels will be reported | Up to Day 1095 | 
| Cohort 4: Number of Participants With Serious Adverse Events (SAEs) | An SAE is an adverse event (AE) resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. | Up to Day 1095 | 
| Cohort 4: Number of participants with AESI | Number of participants with AESIs will be reported. | Up to 6 months after vaccination (Up to Day 181) | 
| Cohort 4: Number of Participants With Solicited Local Adverse Events (AEs) | Number of participants with solicited local AEs were reported. Solicited local AE's included pain/tenderness, erythema, and induration/swelling. | Up to 7 days after vaccination on Day 1 (up to Day 8) and Up to 7 days after re-vaccination | 
| Cohort 4: Percentage of Participants with Systemic AEs | Number of participants with solicited systemic AEs were reported. Solicited systemic AEs included headache, fatigue, myalgia, arthralgia, chills, and fever. | Up to 7 days after vaccination on Day 1 (up to Day 8) and up to 7 days after re-vaccination | 
| Cohort 4: Number of Participants With Unsolicited AEs | Number of participants with unsolicited AEs were reported. Unsolicited AEs included all AEs for which the participant was not specifically questioned in the participant diary | Up to 28 days after vaccination on Day 1 (up to Day 29) and Up to 28 days after re-vaccination |