A Prospective Study to Evaluate the Safety of a New Monovalent 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 monovalent influenza virus vaccine using a new strain recommended for the 2009-2010 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 prospective, randomized, double-blind, placebo-controlled release study enrolled 300 healthy adults 18 to 49 years of age. Eligible participants were randomly assigned in a 4:1 fashion to receive a single dose of monovalent vaccine or placebo by intranasal spray. This study was conducted at multiple sites in the United States. Randomization was stratified by site. Each participant received one dose of investigational product on Day 1. The duration of study participation for each participant was the time from receipt of investigational product through 180 days after receipt of investigational product.

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

Conditions
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Healthy

Intervention / Treatment
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* Biological: Monovalent 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 investigational product administration Healthy by medical history and physical exam Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act [HIPAA] in the United States of America [USA], European Union [EU] Data Privacy Directive in the EU) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations Females of childbearing potential, unless surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy), had sterile male partner, were premenarchal or at least 2 years postmenopausal, or practiced abstinence, must have used 2 effective methods of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, or use of a condom with spermicide by the sexual partner) for at least 30 days prior to dosing with investigational product, and must have agreed to continue using such precautions for at least 90 days after dosing with investigational product; cessation of birth control after this point was to be discussed with a responsible physician. The subject must also have had a negative serum or urine pregnancy test within 14 days prior to investigational product administration (if screening and administration of investigational product did not occur on the same day) and on the day of investigational product administration prior to randomization Males, unless surgically sterile, must have used 2 effective methods of birth control with a female partner and must have agreed to continue using such contraceptive precautions for at least 30 days after dosing with investigational product (from Day 1 through Day 31 of the study) 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: 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 was 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 [HIV] infection, or ongoing immunosuppressive therapy History of Guillain-Barré syndrome A household contact who was severely immunocompromised (eg, hematopoietic stem cell transplant recipient, during those periods in which the immunocompromised individual required care in a protective environment); subject should additionally have avoided close contact with severely immunocompromised individuals for at least 21 days after receipt of investigational product Receipt of any investigational agent within 30 days prior to randomization, or expected receipt through 30 days after the dose of investigational product (use of licensed agents for indications not listed in the package insert was permitted) Expected receipt of anti-pyretic or analgesic medication on a daily or every other day basis from randomization through 14 days after receipt of investigational product Administration of intranasal medications within 14 days prior to randomization, or expected receipt through 14 days after administration of investigational product Known or suspected mitochondrial encephalomyopathy Nursing mother Any condition (eg, chronic cough, allergic rhinitis) that, in the opinion of the investigator, would have interfered with evaluation of the investigational product or interpretation of subject safety or study results Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals

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: Monovalent influenza virus vaccine<br>Frozen monovalent vaccine containing new strain | Biological: Monovalent influenza virus vaccine<br>* Monovalent 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 the cold-adapted, attenuated, 6:2 reassortant influenza strain B/Brisbane/60/2008 (Victoria lineage).<br>|
| Placebo Comparator: Placebo<br>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 Participants Reporting Fever, Defined as Oral Temperature ≥ 101°F | The percentage of subjects with fever was compared between the two treatment groups based on the upper limit of the two-sided 95% exact confidence interval (CI) for the rate difference (monovalent vaccine minus placebo). The upper limit of the two-sided 95% CI was evaluated against the pre-specified equivalence criterion of 5 percentage points which corresponded to the following hypotheses: - H0 (null): rate difference ≥ 5 percentage points, - HA (alternative): rate difference < 5 percentage points. | Days 1-8 after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE) | Solicited symptoms were collected from administration of investigational product through Study Day 15. For this study, solicited symptoms included: fever (> 100°F oral), runny nose, sore throat, cough, vomiting, muscle aches, chills, decreased activity (tiredness), headache. | Days 1-8 after vaccination | 
| Number of Participants Reporting Any Solicited Symptom or at Least One AE |  | Days 1-15 after vaccination | 
| Number of Participants Reporting at Least One Serious Adverse Event (SAE) or New Onset Chronic Disease (NOCD) | 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 important 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 NOCD was a newly diagnosed medical condition of a chronic, ongoing nature and assessed by the investigator as medically significant. | Days 1-29 after vaccination | 
| Number of Participants Reporting at Least One Serious Adverse Event (SAE) or New Onset Chronic Disease (NOCD) | 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 important 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 NOCD was a newly diagnosed medical condition of a chronic, ongoing nature and assessed by the investigator as medically significant. | Days 1-181 after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza, FluMist