A Study of an Adenovirus Serotype 26 Pre-fusion Conformation-stabilized F Protein (Ad26. RSV. preF) Based Respiratory Syncytial Virus (RSV) Vaccine in the Prevention of Lower Respiratory Tract Disease in Adults Aged 60 Years and Older

Study Overview
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Brief Summary
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The study will enroll up to 27,200 participants in order to demonstrate the efficacy of the active Ad26.RSV.preF-based study vaccine in the prevention of Reverse Transcription Polymerase Chain Reaction (RT-PCR) confirmed Respiratory Syncytial Virus (RSV)-mediated Lower Respiratory Tract Disease (LRTD) when compared to placebo in adults aged 60 years and above.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 3 Efficacy Study of an Ad26.RSV.preF-based Vaccine in the Prevention of Lower Respiratory Tract Disease Caused by RSV in Adults Aged 60 Years and Older

Conditions
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Respiratory Syncytial Viruses, Lower Respiratory Tract Disease

Intervention / Treatment
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* Biological: Adenovirus serotype 26 (Ad26)-based respiratory syncytial virus (RSV). preF
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be able to work with smartphones/tablets/computers From the time of vaccination through 3 months after vaccination, participant agrees not to donate blood Must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study Before randomization, a participant must be: a. postmenopausal (postmenopausal state is defined as no menses for 12 months without an alternative medical cause); and b. not intending to conceive by any methods Participants must sign an Inform Consent Form (ICF) indicating that the participant understands the purpose, procedures and potential risks and benefits of the study, and is willing to participate in the study Exclusion Criteria: Has a serious clinically unstable condition, (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, confound, or limit the protocol specified assessments 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, 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 Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator, or an employee of the sponsor Contraindication to Intramuscular (IM) injections and blood draws (example, bleeding disorders) Known or suspected 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: 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: Group 1: Respiratory Syncytial Virus (RSV) vaccine<br>All participants in the active group will receive a single dose intramuscular (IM) injection of study vaccine on Day 1. | Biological: Adenovirus serotype 26 (Ad26)-based respiratory syncytial virus (RSV). preF<br>* Participants will receive a single IM injection of an RSV vaccine.<br>|
| Placebo Comparator: Group 2: Placebo<br>All participants in the placebo group will receive a single IM injection of matching placebo on Day 1. | Biological: Placebo<br>* Participants will receive a single IM injection of matching placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) confirmed Respiratory Syncytial Virus (RSV) mediated Lower Respiratory Tract Disease (LRTD) | Percentage of participants with protocol defined RT-PCR confirmed RSV mediated LRTD will be reported. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Serious Adverse Events (SAEs) | An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. 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. | Up to 6 months | 
| Percentage of Participants with Adverse Events of Special Interest (AESIs) | Percentage of participants with AESIs will be reported. Confirmed thrombosis with thrombocytopenia syndrome (TTS) is considered to be an AESI in this study. | Up to 6 months | 
| Percentage of Participants with Solicited Local Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs are pre-defined local (at the injection site) AEs for which participants will be specifically questioned and which will be noted by participants in their ediary for 7 days post vaccination (day of vaccination and the subsequent 7 days). Solicited local AEs are: injection site pain/tenderness, erythema and swelling at the vaccination site. | 7 days after Vaccination (Day 8) | 
| Percentage of Participants with Solicited Systemic AEs | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Participants will be instructed on how to note signs and symptoms in the electronic diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic events will include fatigue, headache, nausea, and myalgia. | 7 days after Vaccination (Day 8) | 
| Percentage of Participants with Unsolicited AEs | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant eDiary. | 28 days after Vaccination (Day 29) | 
| RSV Neutralizing Antibody Levels | Analysis of neutralizing antibodies to the RSV A strain will be reported. | Up to 24 months | 
| RSV preF and/or postF Protein Binding Antibodies by Enzyme-linked Immunosorbent Assay (ELISA) | Antibodies binding to RSV F protein in pre-fusion and/or post-fusion form will be assessed by ELISA. | Up to 24 months | 
| Interferon Gamma (IFN-gamma) Enzyme-Linked Immunospot (ELISpot) Assay | RSV F-specific cellular immune responses elicited by the different vaccine regimens. | Up to 24 months | 
| Area Under the Curve (AUC) of the Change from Baseline in Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Total Symptom Scale Score | RiiQ is a 4-point scale and it can be scored as a mean of all scores (total symptom scale score) or 2 subscales scores that is respiratory symptoms and systemic symptoms. Respiratory symptoms subscale score is the mean of 6 symptoms, that is, 2 upper respiratory tract infection (URTI) symptoms (nasal congestion and sore throat) and 4 lower respiratory tract infection (LRTI) symptoms (cough, wheezing, shortness of breath, and coughing up phlegm/sputum) whereas systemic symptom subscale score is the mean of 7 systemic symptoms (headache, feeling feverish, neck pain, body aches and pain, fatigue/tiredness, interrupted sleep, and loss of appetite). Each symptom is rated on the scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicating greater severity. The area under the curve during the ARI episode is determined. | Baseline up to 24 months | 
| Percentage of Participants with RT-PCR Confirmed RSV-mediated Acute Respiratory Infection (ARI) | Percentage of participants with RT-PCR confirmed RSV-mediated ARI will be reported. | Up to 24 months | 
| Percentage of Participants with RT-PCR Confirmed RSV-mediated Lower Respiratory Tract Disease (LRTD) During the Second Year | Percentage of participants with RT-PCR confirmed RSV-mediated LRTD during the second year will be reported. | From Month 12 to Month 24 | 
| Percentage of participants with RT-PCR Confirmed RSV-mediated ARI During the Second Year | Percentage of participants with RT-PCR confirmed RSV-mediated ARI during the second year will be reported. | From Month 12 to Month 24 | 
| Percentage of Participants with Predefined Clinically Relevant Disease Associated with RT-PCR-confirmed RSV-mediated ARI Over the Whole Study | Percentage of participants with predefined clinically relevant disease associated with RT-PCR confirmed RSV mediated ARI over the whole study will be reported. | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Acute Respiratory Infections, Ad26.RSV.preF-based Vaccine