A Study of Adenovirus Serotype 26.Respiratory Syncytial Virus.Pre-Fusion F (Ad26.RSV.preF)-Based Vaccine for Prevention of Respiratory Syncytial Virus (RSV) Mediated- Lower Respiratory Tract Disease (LRTD) in Japanese Participants

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy of study vaccine in the prevention of Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)-confirmed RSV mediated- lower Respiratory Tract Disease (LRTD) over one RSV season when compared to placebo in adults aged 60 years and above and to demonstrate the non-inferiority of the vaccine in high-risk adults aged 20 to 59 years versus in adults aged 60 years and older in terms of humoral immune response.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Evaluate Efficacy, Safety, Reactogenicity, and Immunogenicity of an Ad26.RSV.preF-based Vaccine in Japanese Adults Aged 60 Years and Older, and Safety, Reactogenicity, and Immunogenicity of the Vaccine in Japanese Adults Aged 20 to 59 Years at High-risk of RSV Disease

Conditions
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Respiratory Syncytial Virus Prevention

Intervention / Treatment
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* Biological: Ad26/protein preF RSV Vaccine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Participants in Cohort 1 only Must be greater than or equal to (>=60) years old on the day of signing the informed consent form (ICF) and expected to be available for the duration of the study Before randomization, a participant 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 Participants may have underlying illnesses such as hypertension, congestive heart failure (CHF), Chronic obstructive pulmonary disease (COPD), type 2 diabetes, hyperlipoproteinemia, or hypothyroidism, as long as their symptoms and signs are stable and medically controlled in the judgement of the investigator at the time of vaccination, and these conditions receive routine follow-up by the participant's healthcare provider For Participants in Cohort 2 only Must be aged 20 to 59 years (inclusive) on the day of signing the ICF and expected to be available for the duration of the study Has an existing chronic heart or lung condition, without hospitalizations or major medication class change (that is, new or stopped medications) within 30 days prior to screening Participant may have other underlying illnesses 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 Exclusion Criteria: Has a serious clinically unstable condition like, (example, end-stage renal disease with or without dialysis, clinically unstable cardiac disease), Alzheimer's disease, or any other 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 or limit the protocol-specified assessments History of malignancy within 5 years before screening or revaccination 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, which is considered cured with minimal risk of recurrence per investigator's judgement, can be enrolled Had major surgery (example, major cardiopulmonary or abdominal operations) as per the investigator's judgment within 4 weeks before vaccination, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to participate in the study Has an acute illness (including acute respiratory illnesses) or body temperature of >=38.0 degree Celsius (ºC) (>=100.4 Fahrenheit [ºF ] within 24 hours prior to administration of study vaccine) Has had major psychiatric illness and/or drug or alcohol abuse which in the investigator's opinion would compromise the participant's safety and/or compliance with the study procedures

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Interventional Model Description: Cohort 1: adults aged 60 years and older Cohort 2: adults aged 20 to 59 years at high-risk of severe RSV disease
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort (C)1 Group (G)1: Adults, 60 years and older (Ad26/protein preF RSV Vaccine)<br>Participants will receive a single intramuscular (IM) injection of Adenovirus Serotype 26.Respiratory Syncytial Virus.Pre-Fusion F (Ad26/protein preF RSV) vaccine on Day 1. | Biological: Ad26/protein preF RSV Vaccine<br>* Ad26/protein preF RSV vaccine will be administered as an IM injection.<br>* Other names: VAC18193;|
| Placebo Comparator: C1 G2: Adults, 60 years and older (Placebo)<br>Participants will receive a single IM injection of matching placebo on Day 1. | Other: Placebo<br>* Matching Placebo will be administered as an IM injection<br>|
| Experimental: C2 G3: Adults Aged 20 to 59 years at High-risk of Severe RSV Disease (Ad26/protein preF RSV Vaccine)<br>Participants will receive a single IM injection of Ad26/protein preF RSV vaccine on Day 1. | Biological: Ad26/protein preF RSV Vaccine<br>* Ad26/protein preF RSV vaccine will be administered as an IM injection.<br>* Other names: VAC18193;|
| Placebo Comparator: C2 G4: Adults Aged 20 to 59 years at High-risk of Severe RSV Disease (Placebo)<br>Participants will receive a single IM injection of matching placebo on Day 1. | Other: Placebo<br>* Matching Placebo will be administered as an IM injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 2: Neutralizing Antibody Titers Against RSV A Strain as Measured by Virus Neutralizing Antibody (VNA) Assay | Neutralizing antibody titers against RSV A strain as measured by VNA Assay will be reported. | Day 15 | 
| Cohort 1: 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) Over one RSV Season | Number of participants with first occurrence of RT-PCR confirmed RSV Mediated LRTD over one RSV season will be reported. | Until end of RSV season (up to 11.5 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1 (Immuno Subset): Neutralizing Antibody Titers Against RSV A Strain | Neutralizing antibody titers against RSV A strain will be reported. | Day 1, 15, 85, and 169 | 
| Cohort 1 (Immuno Subset) and 2: RSV A F protein in pre-fusion form Binding Antibodies as Assessed by Enzyme linked Immuno Sorbent Assay (ELISA) | Antibodies binding to RSV A F protein in pre-fusion form as assessed by ELISA will be reported | Cohort 1: Day 1, 15, 85, and 169; Cohort 2: 14 days after vaccination (Day 15) | 
| Cohorts 1 and 2: Number of Participants with Serious Adverse Events (SAEs) | A SAE is an 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. | Cohort 1: Up to 6 months after vaccination or end of RSV season, whichever comes later (up to 11.5 months); Cohort 2: Up to 6 months after vaccination | 
| Cohorts 1 and 2: Number of Participants with Adverse Events of Special Interest (AESIs) | Number of participants with AESIs will be reported. Thrombosis with thrombocytopenia syndrome is considered to be an AESI. | Cohort 1: Up to 6 months after vaccination or end of RSV season, whichever comes later (up to 11.5 months); Cohort 2: Up to 6 months after vaccination | 
| Cohort 1 (Safety Subset) and Cohort 2: Number of Participants with Solicited Systemic AEs After Vaccination | Solicited systemic AEs (fatigue, headache, myalgia, nausea and fever) will be noted in the participant diary for 7 days post-vaccination. | 7 Days after vaccination (Day 1 to Day 8) | 
| Cohort 1 (Safety Subset) and Cohort 2: Number of Participants with Solicited Local Adverse Events (AEs) After Vaccination | An AE is any untoward medical occurrence in a clinical study participant administered an investigational or non-investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment. Solicited local AEs (including erythema, swelling, and pain/tenderness at the study vaccine injection site) will be noted in the participant diary for 7 days post-vaccination. | 7 Days after vaccination (Day 1 to Day 8) | 
| Cohort 1 (Safety Subset) and Cohort 2: Number of Participants with Unsolicited AEs After Vaccination | Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary. | 28 days after vaccination (Day 1 to Day 29) | 
| Cohort 2: Neutralizing Antibody Titers Against RSV A Strain iso RSV A2 as Measured by VNA Assay in terms of Seroresponse rate | Neutralizing antibody titers against RSV A strain as measured by VNA assay in terms of seroresponse rate will be reported. Seroresponse is defined as a 4-fold increase from baseline in Day 15 antibody titers. | 14 days after vaccination (Day 15) | 
| Cohort 1: Number of Participants with First Occurrence of RT-PCR Confirmed RSV-mediated Acute Respiratory Infection (ARI) Over one RSV Season | Number of participants with first occurrence of any RT-PCR confirmed RSV-mediated ARI over one RSV season will be reported. | Until end of RSV season (up to 11.5 months) |