Study of a Parenterally Administered H5N1 Influenza Vaccine in Healthy Adults

Study Overview
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Brief Summary
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The safety and tolerability of the pandemic A/H5N1 virosomal vaccine formulated with or without the 3rd generation ISCOM™ adjuvant for parenteral administration will be investigated locally and systemically and by using haematological, biochemical and immunological screening tests. The immunogenicity of the H5N1 vaccine will be assessed through the induction of local and systemic antibody and cellular immune responses. In a pandemic situation, an important aspect is the rapidity of the immune response to the H5N1 vaccine so the detailed kinetics of the immune response will be investigated. The capacity of the vaccine to elicit long lasting immunity and cross reactive immunity to H5 viruses will also be evaluated. Furthermore, the quality of the immune response induced by the vaccine will be studied. The vaccine will be administered as twice the normal human dose (30μg HA) with and without adjuvant, and in a dose sparing manor of half (7.5μg HA) and one tenth (1.5μg HA) of the normal human dose with adjuvant. Sixty subjects will receive two doses of virosomal H5N1 influenza vaccine (separated by 21 ± 4 days) by intramuscular injection into the deltoid muscle. Escalating doses will be separated by a period of one week. Four groups each containing 15 subjects will receive two doses of the pandemic virosomal A/H5N1 influenza vaccine containing: Group 1 30µg HA IM, Group 2 1.5µg HA adjuvanted with 50µg 3rd generation ISCOM™ IM, Group 3 7.5µg HA adjuvanted with 50µg 3rd generation ISCOM™ IM, Group 4 30µg HA adjuvanted with 50µg 3rd generation ISCOM™ IM.

Official Title
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Preparing for an Influenza Pandemic: A Phase I Study of a Parenterally Administered H5N1 Influenza Vaccine in Healthy Adults

Conditions
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Influenza, Healthy

Intervention / Treatment
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* Biological: Influenza vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers (as concluded from the medical history, physical examination, and clinical judgment) aged 19 to 50 years old Females using a reliable method of contraception (from 4 weeks prior to the first vaccination until 4 weeks after the second vaccination) and a negative urine pregnancy test will be required before administration of each dose of vaccine Signed informed consent Subjects able to understand and comply with the study protocol and complete the Adverse Event Form Subjects able to attend the scheduled visits Subjects with normal pre-screening values. If a subjects prescreening samples lie outside the reference values he/she will only be included in the study based upon the medical evaluation of the clinical investigator Exclusion Criteria: Persons with a history of anaphylaxis or serious reactions to any vaccine Persons with known hypersensitivity to any of the vaccine components Persons who have had a temperature >38oC during the previous 72 hours Persons who have had an acute respiratory infection during the last 7 days Women who are pregnant or breast-feeding Persons with chronic illness at any stage that could interfere with trial conduct or compliance Persons who have received blood products or immunoglobulins parenterally during the previous 3 months Persons who have been vaccinated with any vaccine during the 4 weeks preceding the first trial vaccination Persons with known or suspected immunosuppressive disease or who use systemic immunosuppressive drugs Persons taking immunostimulant therapy Persons involved in another clinical trial during the last month. Suspected non-compliance

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 50 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: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>30µg HA vaccine Intramuscularly administered | Biological: Influenza vaccine<br>* Influenza virus strain: avian influenza Influenza A/Vietnam/1194/2004 NIBRG-14<br>|
| Active Comparator: 2<br>1.5µg HA adjuvanted with 50µg 3rd generation ISCOM™ Intramuscularly administered | Biological: Influenza vaccine<br>* Influenza virus strain: avian influenza Influenza A/Vietnam/1194/2004 NIBRG-14<br>|
| Active Comparator: 3<br>7.5µg HA adjuvanted with 50µg 3rd generation ISCOM™ Intramuscularly administered | Biological: Influenza vaccine<br>* Influenza virus strain: avian influenza Influenza A/Vietnam/1194/2004 NIBRG-14<br>|
| Active Comparator: 4<br>30µg HA adjuvanted with 50µg 3rd generation ISCOM™ Intramuscularly administered | Biological: Influenza vaccine<br>* Influenza virus strain: avian influenza Influenza A/Vietnam/1194/2004 NIBRG-14<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicted Adverse Events | The primary endpoints of the trial are the local and systemic adverse events and tolerability of parenterally administered virosomal H5N1 influenza vaccine with or without 3rd generation ISCOM™ adjuvant. | three months | 
| Adverse Events |  | 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of a Non-adjuvanted and 3rd Generation ISCOM™ Adjuvanted Virosomal H5N1 Influenza Vaccine | Number of participants with haemagglutination inhibition tigers >= 32 at the long term time point (1 year post vaccination). | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza A, pandemic, vaccine, immunogenicity, Virus, H5N1