Safety and Immunogenicity of the RSV-F Vaccine in Older Adults Previously Treated With the Same Vaccine or Placebo in the Prior Year.

Study Overview
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Brief Summary
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This study will enroll subjects who received the RSV F vaccine or placebo in the earlier study (RSV-E-201, Year 1) and re-randomize them to receive either vaccine or placebo in a second season. This design will permit evaluation of the safety and immunogenicity of revaccination in a second RSV season, and the safety and immunogenicity of revaccination over two years.

Official Title
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A Phase II Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Immunogenicity and Safety of a Respiratory Syncytial Virus (RSV) Recombinant F Nanoparticle Vaccine in Healthy Older Adult Subjects Previously Treated With the Same Vaccine, or Placebo, in the Prior Year; and to Estimate the Incidence Rate of RSV Disease and Vaccine Efficacy in Subjects Based on Their RSV F Vaccine Experience Over Two Consecutive Years.

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 veterans of the RSV-E-201 clinical trial and 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 SAEs within two months, and Absence of known, current, life-limiting diagnoses that, in the opinion of the investigator, render survival to trial completion 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. The investigator may use his/her discretion to assess potential ability and willingness to comply based on performance in the prior trial, RSV-E-201. Access to inbound and outbound communication by telephone with caregivers and study staff. Exclusion Criteria: Participation in research involving investigational product (drug / biologic / device) within 45 days before planned date of first vaccination, with the exception of participation in the preceding study RSV-E-201. History of a serious reaction to any prior vaccination, or Guillain-Barré syndrome (GBS) within 6 weeks of any prior influenza immunization, or withdrawal from the preceding RSV-E-201 clinical trial due to an adverse event deemed test article-related or at the advice of the investigator. Receipt of any vaccine other than IIV in the 4 weeks preceding the study vaccination; or any RSV vaccine at any time unless administered in the preceding study, RSV-E-201. 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. 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 |
| --- | --- | --- |
| 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 concentration as EU (GMEU) Geometric mean ratio (GMR) Seroresponse rate (SRR) Proportion of subjects with two (2)- and 4-fold seroconversion rates ( SCR2 and SCR4, respectively) | 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, over 56 days post-dosing (Year 2). In addition, MAEs, SAEs, and SNMCs will be collected for 1 year (approximately 364 days) post-dosing | Day 0 to Day 364 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Palivizumab-competitive antibody (PCA) expressed as µg/mL as detected in a competitive ELISA | Summarized by: Geometric mean concentrations (GMC) Geometric mean ratio (GMR) Proportion of subjects with two (2)- and 4-fold seroconversion rates ( SCR2 and SCR4, respectively) | Day 0 to Day 182 | 
| Neutralizing antibody titer to at least one RSV/A and one RSV/B strain. | Summarized by: Geometric mean titer (GMT) Geometric mean ratio (GMR) Proportion of subjects with two (2)- and 4-fold seroconversion rates ( SCR2 and SCR4, respectively) | Day 0 to Day 182 |