Placebo- Controlled Study to Evaluate the Safety and Immunogenicity of the RSV-F Vaccine in Elderly Adults

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and immunogenicity of the RSV- F Vaccine in elderly subjects, as well as rate the incidence of medically- attended RSV disease in vaccine and placebo recipients.

Official Title
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A Phase II Randomized, Observer-Blind, Placebo- Controlled Study to Evaluate the Immunogenicity and Safety of Respiratory Syncytial Virus (RSV) F Vaccine in Healthy Elderly Subjects and to Estimate the Incidence Rate of Medically-attended RSV Disease in Vaccine and Placebo Recipients

Conditions
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Respiratory Syncytial Virus (RSV)

Intervention / Treatment
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* Biological: RSV-F Vaccine
* Biological: Saline 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 residential facilities which 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 serious adverse events (SAEs) within two months, and Absence of known, current, and life-limiting diagnoses which render survival to completion of the protocol unlikely in the opinion of the investigator. 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 within 6 weeks of any prior influenza immunization. Received any vaccine other than an inactivated influenza vaccine in the 4 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 disturbance of coagulation. 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>Saline Placebo (0.5mL Injection) | Biological: Saline Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity as assessed by serum IgG antibody titers specific for the F-Protein antigen | Serum IgG antibody concentrations as ELISA units (EUs) specific for the F protein antigen. Derived/ calculated endpoints based on these data will include: Geometric mean concentrations as EU (GMEU) Geometric mean ratio (GMR) Geometric mean fold-rise( GMFR) Seroresponse rate (SRR) | Day 0 to Day 364 | 
| Number and percentage of subjects with respiratory illness associated with RSV | Defined by any one of rhinorrhea, nasal congestion, pharyngitis, cough, wheezing (or increase in baseline wheezing), sputum production (or increase in the change in nature of baseline sputum production), or new (or worsening) shortness of breath; plus RT-PRC-confirmed RSV infection documented within three days of symptom onset. | Day 0 to Day 364 | 
| Numbers and percentages of subjects with solicited local and systemic AEs. | Solicited local and systemic AEs over the seven days post-injection; and all adverse events, solicited and unsolicited, including adverse changes in clinical laboratory parameters over 56 days post injection. In addition, MAEs, SAEs, and SNMCs will be collected for one year. | Day 0 to Day 364 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Palivizumab competitive antibody responses based on antibody titers in competitive ELISA. | Summarized by geometric mean titer (GMT), GMR. GMFR, and SRR; as well as seroconversion rate (SCR). | Day 0 to Day 182 | 
| Neutralizing antibody titer to at least one prototypical RSV/A and one RSV/B virus strain. | Analyzed by GMT,GMR, SCR, and SRR. Neutralizing antibody assays, because of their time intensive nature, will be performed at a selected subset of time-points. | Day 0 to Day 182 | 
| Hemagglutination-inhibiting (HAI) antibody titers specific for the viruses in the 2014-15 vaccine at Day 28. |  | Day 0 to Day 28 |