Safety of and Immune Response to a Bird Flu Virus Vaccine (H9N2) in Healthy Adults (Study A)

Study Overview
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Brief Summary
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Avian influenza (AI), or bird flu, has recently become a major health concern in Asia and other parts of the world. The purpose of this study is to test the safety of and immune response to a new AI vaccine in healthy adults. Study hypothesis: Influenza A viruses are widely distributed in nature and infect a wide variety of birds and mammals. The direct transmission of avian influenza viruses from birds to humans has recently become a major health concern in Asia and other parts of the world, raising concern of a possible influenza pandemic in humans. This vaccine will evaluate the safety, infectivity and immunogenicity of Live Influenza A vaccine H9N2 (6-2) AA ca reassortant (A/chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca), a cold-adapted, live attenuated virus vaccine administered intranasally for the protection of humans against pandemic influenza viruses of the H9N2 subtype.

Detailed Description
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AI viruses in their natural reservoir in waterfowl are the source from which novel HA and NA subtypes are introduced into the human population, and have the potential to initiate an influenza pandemic. This study will evaluate the safety and immunogenicity of a live, attenuated, cold-adapted reassortant AI virus vaccine, H9N2 (6-2) AA ca Reassortant (A/chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca). Patient participation in this study will be for at least 60 days, with patients followed for at least 42 days after vaccination. In this study, participants will be enrolled sequentially, from highest to lowest dose of vaccine, into one of three groups. At study entry at Day 0, participants will be admitted to the hospital in order to familiarize them with trial procedures. Blood and nasal wash samples will be collected prior to vaccination. On Day 2, participants will have a physical exam and will receive one dose of vaccine; the vaccine will be administered as nose drops. Participants will undergo directed physical examinations daily while they are in the hospital. Nasal washes will also be collected daily from the day of admission through the day prior to discharge to test for the presence of vaccine virus. Participants may be discharged from the hospital after 3 consecutive negative viral cultures, but not before Day 14. Additional blood collection will occur daily from Day 0 to Day 7 and again on Day 21. Participants will return for follow-up visits 28 to 32 days and 42 to 46 days after receiving the vaccine. Blood and nasal wash collection will occur at these 2 study visits, and participants will also have directed physical exams. Depending on the immune response to the first dose of vaccine, some participants may be asked to return to the hospital 1 to 2 months after their first vaccination to receive an additional dose of vaccine.

Official Title
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Phase I Inpatient Study of the Safety and Immunogenicity of H9N2 (6-2) AA ca Reassortant (A/Chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca), a Live Attenuated Virus Vaccine Candidate for Prevention of Avian Influenza H9N2 Infection in the Event of a Pandemic (Study A)

Conditions
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Influenza, Virus Diseases

Intervention / Treatment
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* Biological: H9N2 (6-2) AA ca Reassortant (A/chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Born after 1968 Good general health Available for the duration of the trial Exclusion Criteria: Clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the ability of the volunteer to understand and cooperate with the study Liver, renal, or hematologic disease Alcohol or drug abuse within 12 months of study entry History of severe allergic reaction or anaphylaxis Current asthma or reactive airway disease History of Guillain-Barre syndrome HIV-1 infected Hepatitis C virus infected Positive for hepatitis B surface antigen (HBsAg) Known immunodeficiency syndrome Use of corticosteroids or immunosuppressive drugs within 30 days of study entry. Participants who have used topical corticosteroids are not excluded. Live vaccine within 4 weeks of study entry Killed vaccine within 2 weeks of study entry Absence of spleen Blood products within 6 months of study entry Current smoker Have traveled to the Southern Hemisphere or Asia within 30 days prior to study entry Have traveled on a cruise ship within 30 days prior to study entry Work in the poultry industry Investigational agents within 60 days prior to study entry, or currently participating in another investigational vaccine or drug trial Allergy to eggs or egg products Purified protein derivative (PPD) positive (positive tuberculosis [TB] test) Family member with immunodeficiency Other condition that, in the opinion of the investigator, would affect the participant's participation in the study Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>One vaccination with H9N2 (6-2) AA ca Reassortant (A/chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca) vaccine at a dose of 10^7 TCID50 delivered by nose drops. | Biological: H9N2 (6-2) AA ca Reassortant (A/chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca)<br>* Live attenuated H9N2 (6-2) AA ca Reassortant (A/chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca) vaccine<br>|
| Experimental: 2<br>One vaccination with H9N2 (6-2) AA ca Reassortant (A/chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca) vaccine at a dose of 10^7 TCID50 delivered by nose drops. This Arm will enroll 4 weeks after Arm 1. Enrolled volunteers must have participated in Arm 1. | Biological: H9N2 (6-2) AA ca Reassortant (A/chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca)<br>* Live attenuated H9N2 (6-2) AA ca Reassortant (A/chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca) vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of vaccine-related reactogenicity events and other adverse effects for each dose of the H9N2 G9/AA ca reassortant vaccine |  | Throughout study | 
| Immunogenicity and infectivity for each dose of the H9N2 G9/AA ca reassortant vaccine |  | Throughout study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare antibody responses |  | At Days 28 and 42 | 
| To determine the number of vaccinees infected with the H9N2 G9/AA ca reassortant vaccine candidate. |  | Throughout study | 
| If 10^7 , 10^5 , and 10^3 TCID50 doses of vaccine are administered, to compare the infectivity rates, safety, and immunogenicity between dose groups, and to estimate the HID50 for this vaccine |  | Throughout study | 
| To determine the phenotypic stability of vaccine virus shed |  | Throughout study | 
| To determine whether immunogenicity is enhanced by a second dose of vaccine, and whether the first dose of vaccine restricts replication of the second dose |  | At study completion | 
| To evaluate T-cell mediated and innate immune responses against the H9N2 G9/AA ca reassortant vaccine candidate |  | Throughout study | 
| To develop a serum bank so that the capacity of the H9N2 G9/AA ca reassortant vaccine candidate to elicit HI and neutralizing antibodies to future H9N2 influenza viruses can be tested |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bird Flu