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

Phase 1
Completed
Conditions
Influenza
Virus Diseases
Interventions
Biological: H9N2 (6-2) AA ca Reassortant (A/chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca)
Registration Number
NCT00110279
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
1H9N2 (6-2) AA ca Reassortant (A/chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca)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.
2H9N2 (6-2) AA ca Reassortant (A/chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca)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.
Primary Outcome Measures
NameTimeMethod
Frequency of vaccine-related reactogenicity events and other adverse effects for each dose of the H9N2 G9/AA ca reassortant vaccineThroughout study
Immunogenicity and infectivity for each dose of the H9N2 G9/AA ca reassortant vaccineThroughout study
Secondary Outcome Measures
NameTimeMethod
To compare antibody responsesAt 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 vaccineThroughout study
To determine the phenotypic stability of vaccine virus shedThroughout 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 doseAt study completion
To evaluate T-cell mediated and innate immune responses against the H9N2 G9/AA ca reassortant vaccine candidateThroughout 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 testedThroughout study

Trial Locations

Locations (1)

Johns Hopkins School of Public Health

🇺🇸

Baltimore, Maryland, United States

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