A Prospective Study to Evaluate the Safety of a New Trivalent Intranasal Influenza Vaccine

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 a new strain recommended for the 2008-2009 influenza season not previously contained in the trivalent intranasal FluMist vaccine. Three hundred healthy adults received a single dose of vaccine or placebo and were followed for 180 days.

Detailed Description
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This was a prospective, randomized, double-blind, placebo-controlled release study. Eligible subjects were randomly assigned in a 4:1 fashion to receive a single dose of trivalent vaccine or placebo by intranasal spray. Randomization was stratified by site. Each subject received 1 dose of study vaccine on Study Day 0. The duration of study participation for each subject was the time from study vaccination through 180 days after study vaccination.

Official Title
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A Prospective, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety of a Trivalent Vaccine of New 6:2 Influenza Virus Reassortants in Healthy Adults

Conditions
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Influenza

Intervention / Treatment
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* Biological: Trivalent influenza virus vaccine
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 to 49 years of age (not yet reached their 50th birthday) at the time of study vaccination Healthy by medical history and health assessment Sexually active females, unless surgically sterile or at least 1 year post-menopausal, must have used an effective method of avoiding pregnancy (including oral, implanted, injectable, or transdermal contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) for at least 30 days prior to study vaccination, and must agree to continue using such precautions for at least 90 days after study vaccination; the subject must also have a negative serum or urine pregnancy test within 14 days prior to study vaccination (if screening and study vaccination do not occur on the same day) and on the day of study vaccination prior to randomization Sexually active males, unless surgically sterile, must use an effective method of birth control (condom or abstinence) and must agree to continue using such precautions for at least 30 days after study vaccination Available by telephone Provide written informed consent (and HIPAA authorization, if applicable) 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 study vaccination as required by the protocol Exclusion Criteria: History of hypersensitivity to any component of the vaccine, including egg or egg protein 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 HIV 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); subject should additionally 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 180 days after study vaccination (use of licensed agents for indications not listed in the package insert is permitted) Expected receipt of anti-pyretic or analgesic medication on a daily or every other day basis from randomization through 14 days after study vaccination Note: A daily dose of up to 81 mg of aspirin for prophylactic use is not considered a contraindication to enrollment. Administration of intranasal medications within 14 days prior to randomization, or expected receipt through 14 days after study vaccination Nursing mother Employee of the research center, any individual involved with the conduct of the study, or any family member of such individuals Any condition (eg, chronic cough, allergic rhinitis) that, in the opinion of the investigator, would interfere with evaluation of the vaccine or interpretation of study results

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: Trivalent influenza virus vaccine<br>Frozen trivalent vaccine containing new strains | Biological: Trivalent influenza virus vaccine<br>* Trivalent vaccine was 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 three cold-adapted, attenuated, 6:2 reassortant influenza strains A/South Dakota/6/07 (H1N1), A/Uruguay/716/07 (H3N2), and B/Florida/4/2006.<br>|
| Placebo Comparator: Placebo<br>treatment with placebo | Biological: Placebo<br>* Placebo was supplied in intranasal sprayers containing 0.5 ml of sucrose-phosphate buffer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Fever | Fever was defined as oral temperature greater than or equal to 101 degrees Fahrenheit. | Days 0-7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting All Solicited Symptoms Post-treatment Days 0-7 |  | Days 0-7 | 
| Number of Subjects Reporting Any Adverse Event (AE) Post-treatment |  | Days 0-7 | 
| Number of Subjects Reporting All Solicited Symptoms Post-treatment Days 0-14 |  | Days 0-14 | 
| Number of Subjects Reporting Any AEs Post Treatment |  | Days 0-14 | 
| Number of Subjects Reporting Serious Adverse Events (SAEs) and Significant New Medical Conditions (SNMC) | SAEs were those that resulted in death; were life-threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly/birth defect in the offspring of a study participant; or were an medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed above. An SNMC was a newly diagnosed medical condition of a chronic, ongoing nature and assessed by the investigator as medically significant. | Days 0-28 | 
| Number of Subjects Reporting SAEs and SNMCs | SAEs were those that resulted in death; were life-threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly/birth defect in the offspring of a study participant; or were an medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed above. An SNMC was a newly diagnosed medical condition of a chronic, ongoing nature and assessed by the investigator as medically significant. | Days 0-180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, FluMist, vaccine, prevention, trivalent