A Study of an Ad26.RSV.preF-based Regimen in the Prevention of Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)-Confirmed Respiratory Syncytial Virus (RSV)-Mediated Lower Respiratory Tract Disease in Adults Aged 65 Years and Older

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the efficacy of active study vaccine in the prevention of reverse transcriptase polymerase chain reaction (RT-PCR) confirmed respiratory syncytial virus (RSV)-mediated lower respiratory tract disease (LRTD), when compared to placebo.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 2b Study to Assess the Efficacy, Immunogenicity and Safety of an Ad26.RSV.preF-based Regimen in the Prevention of RT PCR-confirmed RSV-mediated Lower Respiratory Tract Disease in Adults Aged 65 Years and Older

Conditions
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Respiratory Syncytial Viruses, Respiratory Tract Diseases

Intervention / Treatment
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* Biological: RSV Vaccine
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must have a body mass index (BMI) less than (<)40 kilogram per meter square (kg/m^2) Before randomization, a woman must be: postmenopausal (postmenopausal state is defined as no menses for 12 months without an alternative medical cause); and not intending to conceive by any methods Participant must be either in good or stable health. Participants may have mild to moderate underlying illnesses such as chronic cardiac diseases and chronic lung disease (asthma and chronic obstructive pulmonary disease [COPD]), congestive heart failure (CHF), hypertension, type 2 diabetes mellitus, hyperlipoproteinemia, or hypothyroidism, as long as their symptoms and signs are stable and medically controlled in the judgment of the investigator. Participants will be included on the basis of physical examination, medical history, and vital signs performed between informed consent form (ICF) signature and vaccination on Day 1 From the time of vaccination through 3 months after vaccination, participant agrees not to donate blood Participant must be able to read, understand, and complete questionnaires in the eDiary (or a paper safety diary, if designated by the sponsor) Participant must be willing to provide verifiable identification, have means to be contacted and to contact the investigator during the study Exclusion Criteria: Participant has an acute illness (including acute respiratory illnesses) or body temperature greater than or equal to (>=)38.0 degree Celsius (ºC) within 24 hours prior to administration of study vaccine. In such a situation, enrollment at a later date is permitted Participant has a severe or potentially life-threatening chronic disorder such as severe chronic cardiac diseases and severe chronic lung disease (asthma and COPD), advanced CHF, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, Alzheimer's disease, or has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example: compromise well-being) or that could prevent, limit, or confound the protocol-specified assessments Participant has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence) Per medical history, participant has chronic active hepatitis B or hepatitis C infection Per medical history, participant has human immunodeficiency virus (HIV) type 1 or type 2 infection Participant has a known allergy, or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine components (including any of the constituents of the study vaccine)

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: RSV Vaccine<br>Participants will receive a single intramuscular (IM) injection of an adenovirus serotype 26 (Ad26)-based respiratory syncytial virus (RSV) vaccine at a single dose level on Day 1. Participants will then be divided into revaccination subcohorts: 1A, 1B, and 1C to receive revaccination with Ad26.RSV.preF based vaccine at 1 year, 2 years, and 3 years respectively after the first vaccination. | Biological: RSV Vaccine<br>* Participants will receive a single IM injection of an Ad26-based RSV vaccine at a single dose level on Day 1 and revaccination after either 1 year, 2 years, or 3 years.<br>|
| Placebo Comparator: Group 2: Placebo<br>Participants will receive a single IM injection of placebo control on Day 1. Participants will then be divided into revaccination subcohorts 2A, 2B, and 2C, and will first receive Ad26.RSV.preF based vaccine at years 1, 2, and 3. In subcohorts 2A and 2B, participants will receive a revaccination one year later with either Ad26.RSV.preF based vaccine, study vaccine A or study vaccine B. | Biological: RSV Vaccine<br>* Participants will receive a single IM injection of an Ad26-based RSV vaccine at a single dose level on Day 1 and revaccination after either 1 year, 2 years, or 3 years.<br>Biological: Placebo<br>* Participants will receive a single IM injection of placebo control on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With First Occurrence of Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)-Confirmed Respiratory Syncytial Virus (RSV) Mediated Lower Respiratory Tract Disease (LRTD) | Number of participants with first occurrence of RT-PCR-confirmed RSV mediated LRTD according to case definition-1, 2 and 3 were reported. Case definition 1 was defined as having a new onset or worsening in 3 or more symptoms of lower respiratory tract infection (LRTI) ; Case definition 2 was defined as having a new onset or worsening in greater than or equal to (>=) 2 symptoms of LRTI; and Case definition 3 was defined as having a new onset or worsening in >=2 OR >=1 symptoms of LRTI with >=1 systemic symptoms. Systemic symptoms (fatigue/malaise and fever/feverishness) and symptoms of LRTI (cough, shortness of breath, sputum production, wheezing and tachypnea) were collected via the RiiQ. RiiQ symptom scale was a 13-items questionnaire rated on a 4-point scale. Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. The total LRTD symptom score was calculated as the mean of the LRTD symptom scores. | From screening up to 2 years 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any RT-PCR-confirmed RSV Disease |  | From screening up to end of the study (up to 3 years 9 months) | 
| RSV A2 Strain Neutralization Antibody Titers |  | From screening up to end of the study (up to 3 years 9 months) | 
| Pre-Fusion Immunoglobulin G (IgG) Serum Antibody Response as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) |  | From screening up to end of the study (up to 3 years 9 months) | 
| Post-Fusion IgG Serum Antibody Response as Assessed by ELISA |  | From screening up to end of the study (up to 3 years 9 months) | 
| Interferon-gamma (IFN-gamma) T-Cells Responses Analyzed by Enzyme-linked Immunospot Assay (ELISpot) |  | From screening up to end of the study (up to 3 years 9 months) | 
| Number of Participants With Solicited Local Adverse Events (AEs) up to 7 Days After First Vaccination | An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Solicited local AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs included erythema, swelling/induration, and pain/tenderness. Per protocol, all solicited local AEs were considered as related to intervention. | Up to Day 8 (7 days after first vaccination on Day 1) | 
| Number of Participants With Solicited Systemic AEs up to 7 Days After First Vaccination | An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Solicited systemic AEs included fatigue, headache, myalgia, arthralgia, and fever (defined as an endogenous elevation of body temperature >=38.0°C, as recorded in at least one measurement). | Up to Day 8 (7 days after first vaccination on Day 1) | 
| Number of Participants With Unsolicited AEs up to 28 Days After First Vaccination | An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Unsolicited adverse events included all adverse events for which the participant is not specifically questioned in the participant diary. | Up to Day 29 (28 days after first vaccination on Day 1) | 
| Number of Participants With Solicited Local AEs 7 Days After Re-vaccination at 1, 2 and 3 Years |  | 7 days after re-vaccination at 1, 2 and 3 years | 
| Number of Participants With Solicited Systemic AEs 7 Days After Re-vaccination at 1, 2 and 3 Years |  | 7 days after re-vaccination at 1, 2 and 3 years | 
| Number of Participants With Unsolicited AEs 28 Days After Re-vaccination at 1, 2 and 3 Years |  | 28 days after re-vaccination at 1, 2 and 3 years | 
| Number of Participants With Serious Adverse Events (SAEs) During the RSV Season |  | From screening up to end of the study (up to 3 years 9 months) | 
| Number of Participants With Adverse Events of Special Interests (AESI) During the RSV Season |  | From screening up to end of the study (up to 3 years 9 months) | 
| Number of Participants With SAE During ARI Follow-up Period |  | Up to 2 years 9 months |