MVA-BN-RSV Vaccine Trial

Study Overview
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Brief Summary
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Phase 3 randomized, double blind study comparing recombinant MVA-BN-RSV vaccine vs placebo for efficacy and safety in adults >=60 years of age

Official Title
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A Randomized, Double-blind, Phase 3 Trial to Assess Clinical Efficacy, Safety and Reactogenicity of the Recombinant MVA-BN® -RSV Vaccine in Adults ≥60 Years of Age

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Biological: MVA-BN-RSV vaccine
* Biological: Tris Buffered Saline (TBS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects ≥60 years of age. Informed Consent signed by the subject. Subjects may have one or more chronic medical conditions e.g., mild to moderate underlying illnesses such as chronic cardiac diseases and chronic lung disease (asthma and chronic obstructive pulmonary disease [COPD]), congestive heart failure (CHF), hypertension, type 2 diabetes mellitus, hyperlipoproteinemia, or hypothyroidism, that is clinically stable as assessed by the investigator. Absence of known, current, and life-limiting diagnoses that render survival to completion of the protocol unlikely. Ability to comply with trial requirements, which necessitates access to transportation to on-site visits, including symptom visits for a nasopharyngeal swab. Willingness and ability to utilize an application on a personal device (i.e., smartphone, tablet, etc.) or a provisioned device to record solicited events and record all per protocol required data during the surveillance period. For women of childbearing potential (WOCBP), agreement to use an acceptable method of contraception during the trial and a negative urine pregnancy test within 24 hours prior to vaccination. Exclusion Criteria: History of or current clinical manifestation of any serious medical condition that in the opinion of the investigator would compromise the safety of the subject, confound data interpretation, or would limit the subject's ability to complete the trial. History of or active autoimmune disease, including diabetes mellitus type I. Vitiligo or hypothyroidism requiring thyroid replacement therapy are not exclusions. Rheumatoid arthritis not requiring immunomodulatory and/or immunosuppressant treatment is not an exclusion. Known or suspected impairment of immunologic functions, including chronic inflammatory bowel disorders. Clinically significant mental disorder that would prevent patients from giving informed consent and complying with study procedures (e.g., completion of the electronic diary). Active or recent (within 6 months before enrollment) history of chronic alcohol abuse. History of a serious reaction to any prior vaccination or Guillain-Barré syndrome (GBS) within 6 weeks of any prior influenza immunization. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g., tris(hydroxymethyl)-amino methane, chicken embryo fibroblast proteins, gentamycin, ciprofloxacin; this includes: Known allergy to eggs or aminoglycosides History of anaphylaxis or severe allergic reaction to any vaccine Any administration or planned administration of: A licensed live or vector-based vaccine within 30 days prior to or after trial vaccine administration. A licensed inactivated or ribonucleic acid (RNA)-based vaccine within 14 days prior to or after trial vaccine administration. Previous vaccination with an RSV vaccine, or any planned vaccination with an RSV vaccine other than the trial vaccine. Planned chronic, systemic administration (defined as more than 14 days) of >10 mg prednisone (or equivalent)/day or any other systemic use of immunemodifying drugs during a period starting from 3 months prior to first administration of the trial vaccine and ending at the End of Study Visit (EOS). The use of topical, inhaled, ophthalmic and nasal glucocorticoids is permitted. Administration or planned administration of immunoglobulins and/or any blood products during a period starting from 3 months prior to first administration of the trial vaccine and during the trial. Known uncontrolled coagulation disorder. Anticoagulant treatment under adequate control for cardiovascular prophylaxis or prophylaxis of thromboembolic disease or stroke in the setting of atrial fibrillation are permitted. Use of any investigational or non-registered drug or vaccine other than the trial vaccine within 30 days prior to the administration of the trial vaccine, or planned administration of such a drug or vaccine between enrollment in the trial and until the end of the clinical trial including follow-up. [For US Only] Involvement with this trial as research personnel.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Single dose MVA-BN-RSV<br>Single dose (Week 0): MVA-BN-RSV virus with a titer of at least 3x10E8 Inf.U/0.5mL (intramuscular vaccination) | Biological: MVA-BN-RSV vaccine<br>* One injection, suspension for injection, intramuscular use, 0.5mL MVA-BN-RSV virus with a titer of at least 3 x 10E8 infectious units (Inf.U)/0.5mL in a Tris buffer at pH 7.7.<br>|
| Experimental: Group 2: Single dose Placebo<br>Single dose of TBS (intramuscular injection; 0.5mL) | Biological: Tris Buffered Saline (TBS)<br>* One injection, solution for injection, intramuscular use, 0.5mL TBS, pH 7.7.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of LRTD | Occurrence of LRTD associated with RSV until the end of one RSV season (at least 6 months, and up to 12 months post vaccination). | Over one RSV season (at least 6 months, and up to 12 months post vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of ARD | Occurrence of ARD associated with RSV until the end of one RSV season (at least 6 months, and up to 12 months post vaccination). | Over one RSV season (at least 6 months, and up to 12 months post vaccination) | 
| Occurrence of complications and hospitalizations | Occurrence of complications and hospitalizations related to PCR-confirmed RSV disease. | Over one RSV season (at least 6 months, and up to 12 months post vaccination) | 
| Occurrence of any serious adverse events | Occurrence of any serious adverse events at any time during the trial period. | Up to 24 months after vaccination | 
| Occurrence of any grade 3 or higher adverse events | Occurrence of any grade 3 or higher adverse events assessed as related to study vaccine within 29 days after vaccination. | Within 29 days after vaccination | 
| Occurrence of solicited local adverse events | Occurrence of solicited local adverse events (pain, swelling, pruritus, erythema, induration) within 8 days after vaccination. | Within 8 days after vaccination | 
| Occurrence of solicited systemic adverse events | Occurrence of solicited systemic adverse events (body temperature, headache, fatigue, myalgia, nausea, chills) within 8 days after vaccination. | Within 8 days after vaccination | 
| Occurrence of any unsolicited adverse events | Occurrence of any unsolicited adverse events within 29 days after vaccination. | Within 29 days after vaccination | 
| RSV-specific T-cell responses | RSV-specific T-cell responses measured 1 week post vaccination in a subset of the study population | Within 1 week after vaccination | 
| RSV-specific serum IgG antibody titers | RSV-specific serum IgG antibody titers 2 weeks post vaccination in a subset of the study population | 2 weeks after vaccination | 
| RSV-specific serum neutralizing antibody titers | RSV-specific serum neutralizing antibody titers 2 weeks post vaccination (subtype A and B) | Within 2 weeks after vaccination |