A Study to Evaluate the Safety of 3 New 6:2 Influenza Virus Reassortants in Adults

Study Overview
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Brief Summary
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This prospective annual release study was designed to assess the safety of a trivalent influenza virus vaccine using two new strains recommended for the 2012-2013 influenza season not previously contained in the trivalent intranasal FluMist vaccine. Three hundred healthy adults will receive a single dose of vaccine or placebo and will be followed for 180 days after study vaccination.

Detailed Description
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This prospective, randomized, double-blind, placebo-controlled release study will enroll approximately 300 healthy adults 18 to 49 years of age. Eligible subjects will be randomly assigned in a 4:1 fashion to receive a single dose of trivalent vaccine or placebo by intranasal spray. Randomization will be stratified by site. This study will be conducted at 3 sites in the United States of America. Each subject will receive one dose of investigational product on Study Day 1. The duration of study participation for each subject is the time from study vaccination through 180 days after study vaccination.

Official Title
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A Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Safety of 3 New 6:2 Influenza Virus Reassortants in Adults

Conditions
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Influenza

Intervention / Treatment
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* Biological: Trivalent Influenza Virus Vaccine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 through 49 years at the time of investigational product administration Written informed consent and any locally required authorization (ie, HIPAA in the USA) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations Females of childbearing potential who are sexually active with a nonsterilized male partner must use effective contraception for 30 days prior to study vaccination, and must agree to continue using such precautions for 60 days after study vaccination Nonsterilized males who are sexually active with a female partner of child-bearing potential must use an effective method of contraception from prior to study vaccination amd must agree to continue using such precautions for at least 30 days after receipt study vaccination Healthy by medical history and physical examination Female subjects of child-bearing potential must also have a negative urine or blood pregnancy test at screening and, if screening and Day 1 do not occur on the same day, on the day of vaccination prior to randomization. Subject available by telephone Ability to understand and comply with the requirements of the protocol, as judged by the investigator Ability to complete follow-up period of 180 days after dosing as required by the protocol Exclusion Criteria: Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results Concurrent enrollment in another clinical study up to 180 days after receipt of investigational product (Day 181) Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals History of hypersensitivity to any component of the vaccine, including egg or egg protein or serious, life threatening, or severe reactions to previous influenza vaccinations History of hypersensitivity to gentamicin Any condition for which the inactivated influenza vaccine is indicated, including chronic disorders of the pulmonary or cardiovascular systems (eg, asthma), chronic metabolic diseases (eg, diabetes mellitus), renal dysfunction, or hemoglobinopathies that required regular medical follow-up or hospitalization during the preceding year Acute febrile (> 100.0°F oral or equivalent) and/or clinically significant respiratory illness (eg, cough or sore throat) within 14 days prior to randomization Any known immunosuppressive condition or immune deficiency disease, including human immunodeficiency virus infection, or ongoing immunosuppressive therapy History of Guillain-Barré syndrome A household contact who is severely immunocompromised (eg, hematopoietic stem cell transplant recipient, during those periods in which the immunocompromised individual requires care in a protective environment); additionally, subject should avoid close contact with severely immunocompromised individuals for at least 21 days after study vaccination Receipt of any investigational agent within 30 days prior to randomization, or expected receipt through 30 days after study vaccination (use of licensed agents for indications not listed in the package insert is permitted) Receipt of any non-study vaccine within 30 days prior to randomization, or expected receipt through 30 days after study vaccination Expected receipt of antipyretic or analgesic medication on a daily or every other day basis from randomization through 14 days after study vaccination Administration of intranasal medications within 14 days prior to randomization, or expected receipt through 14 days after study vaccination Receipt of influenza antiviral therapy or antiviral agents within 48 hours prior to study vaccination or expected receipt of influenza antiviral therapy or antiviral agents through 14 days after study vaccination Known or suspected mitochondrial encephalomyopathy Nursing mother

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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trivalent Influenza Virus Vaccine<br>Trivalent vaccine is supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose phosphate buffer, egg allantoic fluid and approximately 10^7 FFU (fluorescent focus units) of each of 3 cold-adapted, attenuated 6:2 reassortant influenza strains: A/H1N1 (A/California/7/2009), A/H3N2 (A/Victoria/361/2011), B (B Wisconsin/1/2010). A single dose of investigational product was administered on Day 1. | Biological: Trivalent Influenza Virus Vaccine<br>* Trivalent vaccine is supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose phosphate buffer, egg allantoic fluid and approximately 10^7 FFU (fluorescent focus units) of each of 3 cold-adapted, attenuated 6:2 reassortant influenza strains: A/H1N1 (A/California/7/2009), A/H3N2 (A/Victoria/361/2011), B (B Wisconsin/1/2010). A single dose of investigational product was administered on Day 1.<br>|
| Placebo Comparator: Placebo<br>Placebo is suppllied in intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer. A single dose of investigational product was administered on Day 1. | Other: Placebo<br>* Placebo is suppllied in intranasal sprayers containing 0.5 mL of sucrose-phosphate buffer. A single dose of investigational product was administered on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Reporting Fever Within 7 Days Post Vaccination | A comparison of the rate of fever, defined as oral temperature greater than or equal to 101 degrees Fahrenheit, reported during the 7 days post administration of investigational product between the trivalent influenza virus vaccine and placebo groups. | Study Days 1 - 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Reporting Other Solicited Symptoms Within 7 Days Post Vaccination | Solicited symptoms were events that were considered likely to occur post dosing. Solicited symptoms for this study are listed below. | Study Days 1- 8 | 
| Percentage of Participants Reporting Any Adverse Event (AE) Within 7 Days Post Vaccination | Percentage of participants reporting at least one AE between Days 1 and 8. Investigational product was administered on Day 1. | Study Days 1 - 8 | 
| Percentage of Participants Reporting Other Solicited Symptoms Within 14 Days Post Vaccination | Solicited symptoms were events that were considered likely to occur post dosing. Solicited symptoms for this study are listed below. | Study Days 1 - 15 | 
| Percentage of Participants Reporting Any Adverse Event (AE) Within 14 Days Post Vaccination | Percentage of participants reporting at least one AE between Days 1 and 15. Investigational product was administered on Day 1. | Study Days 1 - 15 | 
| Percentage of Participants Reporting Any Serious Adverse Event (SAE) Within 28 Days Post Vaccination | Percentage of participants reporting at least one SAE between Days 1 and 29. Investigational product was administered on Day 1. | Study Days 1 - 29 | 
| Percentage of Participants Reporting Any Serious Adverse Event (SAE) Within 180 Days Post Vaccination | Percentage of participants reporting at least one SAE between Days 1 and 181. Investigational product was administered on Day 1. | Study Days 1 - 181 | 
| Percentage of Participants Reporting Any New Onset Chronic Diseases (NOCDs) Within 28 Days Post Vaccination | An NOCD was a newly diagnosed medical condition of a chronic, ongoing nature and assessed by the investigator as medically significant. Such events were assessed between Day 1 and Day 29. Investigational product was administered on Day 1. | Study Days 1 - 29 | 
| Percentage of Participants Reporting Any New Onset Chronic Diseases (NOCDs) Within 180 Days Post Vaccination | An NOCD was a newly diagnosed medical condition of a chronic, ongoing nature and assessed by the investigator as medically significant. Such events were assessed between Day 1 and Day 181. Investigational product was administered on Day 1. | Study Days 1 - 181 | 
| Percentage of Participants Who Used Antipyretic or Analgesic Agents Within 7 Days Post Vaccination | Percentage of participants who used an antipyretic or analgesic agent between Days 1 and 8. Investigational product administration occurred on Day 1. | Study Days 1 - 8 | 
| Percentage of Participants Who Used Antipyretic or Analgesic Agents Within 14 Days Post Vaccination | Percentage of participants who used an antipyretic or analgesic agent between Days 1 and 15. Investigational product administration occurred on Day 1. | Study Days 1 - 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trivalent, Influenza, FluMist, Vaccine, Prevention