A Study to Evaluate the Efficacy of an RSV F Vaccine in Older Adults

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the efficacy of the RSV F vaccine at a dose of 135µg via intramuscular (IM) injection in the prevention of moderate-severe RSV-associated lower respiratory tract disease (RSV-LRTD) in older adults ≥ 60 years of age.

Official Title
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A Study to Evaluate the Efficacy of an RSV F Vaccine in Older Adults

Conditions
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Respiratory Syncytial Virus (RSV)

Intervention / Treatment
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* Biological: RSV-F Vaccine
* Biological: Phosphate Buffer Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥60 years of age who are ambulatory and live in the community, or in assisted-living or long-term care residential facilities that provide minimal assistance, such that the subject is primarily responsible for self-care and activities of daily living. Subjects may have one or more chronic medical diagnoses, but should be clinically stable as assessed by: Absence of changes in medical therapy within one month due to treatment failure or toxicity, Absence of medical events qualifying as SAEs within one month of the planned vaccination on Day 0, and Absence of known, current, and life-limiting diagnoses which, in the opinion of the investigator, render survival to completion of the protocol unlikely. Willing and able (on both a physical and cognitive basis) to give informed consent prior to study enrollment. Able to comply with study requirements; including access to transportation for study visits. Access to inbound and outbound telephone communication with caregivers and study staff. Exclusion Criteria: Participation in research involving investigational product (drug / biologic / device) within 45 days before the planned date of the Day 0 vaccination. History of a serious reaction to any prior vaccination, or Guillain-Barré syndrome (GBS) within 6 weeks of any prior influenza immunization. Receipt of any vaccine other than an IIV in the 4 weeks preceding the study vaccination or a pneumococcal vaccine in the 2 weeks preceding the study vaccination; or any RSV vaccine at any time. Any known or suspected immunosuppressive condition, acquired or congenital, as determined by history and/or physical examination. Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the study vaccine. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose ≥10mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the study vaccine or during the study. Acute disease at the time of enrollment (defined as the presence of a moderate or severe illness with or without fever, or an oral temperature ≥38.0°C on the planned day of vaccine administration). Known uncontrolled disorder of coagulation. Potential subjects receiving aspirin, clopidogrel, prasugrel, dipyridamole, dabigatran, apixaban, rivaroxaban or warfarin under good control for cardiovascular prophylaxis or prophylaxis of thromboembolic disease or stroke in the setting of atrial fibrillation will NOT be excluded. Suspicion or recent history (within one year of planned vaccination) of alcohol or other substance abuse. Any condition that in the opinion of the investigator would pose a health risk to the subject if enrolled or could interfere with evaluation of the vaccine or interpretation of study results (including neurologic, cognitive, or psychiatric conditions deemed likely to impair the quality of study compliance or safety reporting).

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group A<br>RSV-F Vaccine (0.5mL Injection) | Biological: RSV-F Vaccine<br> <br> |
| Placebo Comparator: Treatment Group B<br>Phosphate Buffer Placebo (0.5mL Injection) | Biological: Phosphate Buffer Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numbers and percentages of subjects with moderate-severe RSV-LRTD | Defined by the presence of at least three (3) of: cough, wheezing (or worsening in baseline wheezing), new sputum production (or increase in baseline sputum production), new (or worsening) shortness of breath, and observed tachypnea (≥20 breaths per minute); plus RT-PCR-confirmed RSV infection documented within five days of symptom onset. | Day 0 to Day 182 | 
| Numbers and percentages of subjects with solicited local and systemic AEs | Defined as solicited local and systemic AEs over the 7 days post-injection; all adverse events, solicited and unsolicited over 56 days after dosing; and MAEs, SAEs, and SNMCs over one year post dosing. | Day 0 to Day 364 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numbers and percentages of subjects with RSV-Acute Respiratory Disease (RSV-ARD) | Defined by the presence of at least one (1) of: rhinorrhea, nasal congestion, pharyngitis, cough, wheezing (or worsening in baseline wheezing), new sputum production (or increase in baseline sputum production), new (or worsening) shortness of breath; plus RT-PCR-confirmed RSV infection documented within five days of symptom onset. | Day 0 to Day 182 | 
| RSV F protein antibody expressed as ELISA Units (EU). | Summarized by: Geometric Mean Concentrations as EU (GMEU) Geometric Mean Ratio (GMR) Seroresponse Rate (SRR) | Day 0 to Day 364 | 
| Palivizumab-competitive antibody (PCA) expressed as µg/mL as detected in a competitive ELISA | Summarized by: Geometric Mean Concentrations as EU (GMEU) Geometric Mean Fold Rise (GMFR) | Day 0 to Day 364 | 
| Neutralizing antibody titer to at least one RSV/A and one RSV/B virus strain | Summarized by: Geometric Mean Titer (GMT) Geometric Mean Ratio (GMR) | Day 0 to Day 28 | 
| Number and percentage of subjects with RSV-ARD and/or RSV-LRTD | Summarized by treatment group and by age strata and in strata defined by comorbidities and type of community housing. | Day 0 to Day 364 | 
| Hemagglutination-inhibiting (HAI) antibody titers specific for the viruses in the 2015-16 IIV at Day 28 in the subset of subjects in each treatment group that receive IIV concurrently with study test article. |  | Day 0 to Day 28 |