Safety and Immunogenicity Study of H3N2 M2SR Monovalent Influenza Vaccine in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose is of this study is to assess the safety and tolerability of three dose levels of H3N2 M2SR influenza vaccine versus placebo delivered intranasally to healthy adult subjects.

Detailed Description
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Healthy adult subjects will be screened with the objective to randomize 96 subjects with the lowest levels of H3 hemagglutination inhibition (HAI) titers that meet all inclusion/exclusion criteria and have signed an informed consent. Subjects will be rank ordered from low to high based on their HAI titer. Subjects will then be assigned treatment based on a randomization to either active vaccine or placebo. The first two subjects dosed in each dose cohort will serve as sentinels and will receive active IP (not randomized). Subjects will receive a single dose inoculation of the H3N2 M2SR seasonal monovalent influenza vaccine administered intranasally as a liquid formulation, or placebo (saline). The sentinel subjects will be vaccinated in dose cohort 1 and a safety monitoring committee (SMC) will conduct a review of safety data, tolerability, reactogenicity, and clearance of infectious virus prior to dosing the remaining subjects of the cohort with active or placebo. After the last subject in the cohort has been followed for at least 7 days the SMC will conduct another review of safety data prior to proceeding to the next higher dose level: Cohort 2. The same processes of sentinel subject dosing and SMC review will be conducted for Cohorts 2 and 3.

Official Title
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Phase 1 Clinical Study To Investigate The Safety And Immunogenicity Of The H3N2 (A/Brisbane/10/2007) M2SR Monovalent Influenza Vaccine

Conditions
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Flu

Intervention / Treatment
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* Biological: the H3N2 M2SR monovalent influenza vaccine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Individuals who are in good health at the time of entry into the study as determined by medical history, physical examination, vital signs, and clinical safety laboratory values and clinical judgement of the Principal Investigator (PI) The subject signs and dates a written, informed consent form and any required privacy authorization Willing to use a reliable form of contraception approved by the Investigator (e.g., intrauterine device [IUD], female condom, diaphragm with spermicide, cervical cap, use of condom by the sexual partner or a sterile sexual partner) for 1 month prior to vaccination and until 28 days following the last visit Individuals who are willing and able to communicate with the Investigator and understand the requirements of the study Individuals who can comply with trial procedures and are available for the duration of follow-up Key Exclusion Criteria: Any subject with the following screening lab values (per the Food and Drug Association (FDA) Guidance: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials): Any ≥ Grade 2 abnormality Clinically significant Grade 1 abnormality as judged by the Principal Investigator or Clinically non-significant Grade 1 abnormality as judged by the Principal Investigator which, upon repeat testing becomes more abnormal History or clinical manifestation of clinically significant health conditions including but not limited to: mental illness, active hematological, renal, hepatic, pulmonary, central nervous, neurological, cardiovascular, endocrine (including diabetes mellitus) or gastrointestinal disorders Acute febrile illness within 72 hours prior to vaccination, defined as the presence of a moderate or severe illness with or without fever (as determined by the Investigator through medical history and physical examination), or presence of a fever >38ºC orally. Any confirmed or suspected immunosuppressive or immunodeficient state including: asplenia, recurrent severe infections and chronic (more than 14 days) immunosuppressant medication Living in the same household with any person with a non-functional or suppressed immune system

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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: H3N2 M2SR monovalent influenza vaccine<br>This group will receive a low, medium or high dose of the H3N2 M2SR monovalent influenza vaccine administered intranasally. It will be compared with placebo in a 3:1 ratio. | Biological: the H3N2 M2SR monovalent influenza vaccine<br>* The H3N2 Bris10 M2SR influenza vaccine candidate (Bris10 M2SR) is formulated to contain different levels of an M2-deleted non-replicating influenza virus expressing the HA and NA genes of influenza strain A/Brisbane/10/2007.<br>|
| Experimental: placebo<br>This group will receive saline administered intranasally. | Other: Placebo<br>* saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of local and systemic adverse events (AEs) through 28 days vaccination and cumulatively through Day 180 | Record adverse events | from baseline through study completion (Day 180) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects demonstrating seroconversion to vaccine hemagglutinin antigen and the magnitude of the immune response | Test antibodies pre and post vaccination | from baseline through study completion (Day 180) | 
| Length of time that vaccine virus shedding is detected | Test nasal swabs for virus | at 24, 48 and 72 hours post-vaccination and on day 7 post vaccination |