A Phase I Study to Evaluate the Safety, Reactogenicity, and Humoral Immune Responses to an Inactivated H5N1 Influenza Vaccine

Study Overview
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Brief Summary
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The focus of this study is to evaluate the safety, reactogenicity and humoral immune responses of the study vaccine when administered at the dose of 7.5 µg HA, 15 µg HA, or 30 µg HA to human subjects.

Detailed Description
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Since 1997, avian H5N1 influenza in Southeast Asia has caused several human infections and has a high mortality rate. Experts warn that the next influenza pandemic is imminent and could be severe and prevention and control will depend on the rapid production and worldwide distribution of specific pandemic influenza candidate vaccines. An H5N1 influenza vaccine was successfully produced from whole virus grown in MDCK (Madin-Darby canine kidney) cells. These purified inactivated vaccine antigens were safe and could induce immune responses in animal studies. Moreover, when formulated in aluminum phosphate a stronger response was generated even at low doses in animals (Chong et al., 2008; Hu et al., 2008). However, further investigations are necessary before their human safety and immunogenicity can be established. This human phase I clinical study, therefore, evaluates the safety and immunogenicity of adjuvanted H5N1 virion influenza vaccine.

Official Title
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A Phase I, Prospective, Randomized, Open Label, Observer-Blind, Single Center Study to Evaluate the Safety, Reactogenicity and Immunogenicity of an Inactivated H5N1 Influenza Vaccine Produced in Madin-Darby Canine Kidney (MDCK) Cells

Conditions
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Bird Flu, Avian Influenza, Influenza A(H5N1)

Intervention / Treatment
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* Biological: AT-301


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥20 and ≤60 years of age In good health as determined by medical history, physical examination, and clinical judgment of the investigator Willing and able to comply with all required study visits and follow-up required by this protocol Must provide written informed consent Exclusion Criteria: Known or potential exposure to avian influenza virus or any H5N1 HA antigen vaccine Had any influenza vaccine within 6 months Administered with any vaccine within 30 days A history of hypersensitivity to vaccines or inflammatory or degenerative neurological disease Receiving chronic administration of immunosuppressants or other immune-modifying drugs within 6 months Known HIV, hepatitis B (HBsAg) or hepatitis C seropositivity Any medical illness including clinically significant acute pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests Receiving immunoglobulins and/or any blood products within the three months Acute disease at the time of enrolment Psychiatric, addictive, or any disorder, which may compromise the ability to give a truly informed consent for participation of this study or adequate compliance Breast feeding or pregnant women

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dosage AT-301<br>7.5 µg hemagglutinin (HA) | Biological: AT-301<br>* Inactivated H5N1 Influenza Virion Vaccine<br>|
| Experimental: Middle Dosage AT-301<br>15 µg hemagglutinin (HA) | Biological: AT-301<br>* Inactivated H5N1 Influenza Virion Vaccine<br>|
| Experimental: High Dosage AT-301<br>30 µg hemagglutinin (HA) | Biological: AT-301<br>* Inactivated H5N1 Influenza Virion Vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Signs and symptoms solicited by vaccination | Percentage, intensity, and relationship to vaccination of solicited local and general signs and symptoms during a 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after each administered vaccine. | A 7-day follow-up period after each vaccine administration | 
| Signs and symptoms unsolicited by vaccination | Percentage, intensity, and relationship to vaccination of unsolicited local and general signs and symptoms during a 21-day follow-up period (i.e. day of vaccination and 20 subsequent days) after each administered vaccine. | A 21-day follow-up period after each vaccine administration | 
| Occurrence of adverse events and serious adverse events | Occurrence of overall adverse events and serious adverse events up to 180 days after the first administered vaccine. | Up to 180 days after the first vaccine administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum antibody titers to H5N1 virus | Serum anti-HA antibody titers and neutralizing antibody titers. | Day 0 | 
| Serum antibody titers to H5N1 virus | Serum anti-HA antibody titers and neutralizing antibody titers. | Day 21 | 
| Serum antibody titers to H5N1 virus | Serum anti-HA antibody titers and neutralizing antibody titers. | Day 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Avian Influenza, Influenza A Virus Subtype H5N1, Inactivated H5N1 Influenza Virion Vaccine, Phase I, Preventive H5N1 vaccination