Study to Evaluate the Safety and Immunogenicity of Pandemic Monovalent (H5N1) Influenza Vaccines (Whole Virus Formulation) in Adults 18 and 60 Years of Age

Study Overview
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Brief Summary
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Today, the leading contender for the next pandemic of influenza is H5N1, a strain of avian virus. Prevention and control of a pandemic will depend on the rapid production and worldwide distribution of specific pandemic vaccines. Candidate 'pandemic-like' vaccines must be developed and tested in clinical trials to determine the most optimal formulation and the best vaccination schedule.This study is designed to test in healthy adults aged between 18-60 years the reactogenicity and immunogenicity of one and two administrations of a candidate pandemic H5N1 vaccine formulated from Whole Virus. The vaccines contain different antigen doses. For each dose, adjuvanted vaccine will be compared to the plain vaccine in order to detect the optimal formulation for immunization against the H5N1 influenza strain.

Official Title
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A Partially-blind Multi-centric Study in Adults Aged Between 18-60 Years Designed to Evaluate the Reactogenicity and Immunogenicity of 1 and 2 Doses of Pandemic Monovalent (H5N1) Influenza Vaccines (Whole Virus Formulation) Administered at Different Doses and Adjuvanted or Not

Conditions
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Influenza

Intervention / Treatment
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* Biological: Influenza Monovalent Whole virus (H5N1) adjuvanted vaccine
* Biological: Influenza Monovalent Whole virus (H5N1)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: A male or female between, and including, 18 and 60 years of age at the time of the first vaccination. Healthy subjects as established by medical history and clinical examination before entering into the study. If the subject is female, she must be of non-childbearing potential. Exclusion criteria: Administration of any vaccine during the period starting 15 days before the first administration of the study vaccine and ending 21 after the second one. Administration of an influenza vaccine other than the study vaccines during the entire study period. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first administration of the study vaccine. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination History of hypersensitivity to vaccines. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Acute disease at the time of enrolment. Administration of immunoglobulins and/or any blood products within the three months preceding the first administration of the study vaccine or during the study. lactating women Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days prior to the first vaccination, or planned use during the study period.

Ages Eligible for Study
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Minimum Age: 18 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: H5N1 Formulation 1 Group<br>Subjects in this group received 2 doses of H5N1 adjuvanted formulation 1 vaccine at a 21-day interval | Biological: Influenza Monovalent Whole virus (H5N1) adjuvanted vaccine<br>* 2 doses administered intramuscularly at the deltoid region of the non-dominant arm at Days 0 and 21<br>|
| Experimental: H5N1 Formulation 2 Group<br>Subjects in this group received 2 doses of H5N1 adjuvanted formulation 2 vaccine at a 21-day interval | Biological: Influenza Monovalent Whole virus (H5N1) adjuvanted vaccine<br>* 2 doses administered intramuscularly at the deltoid region of the non-dominant arm at Days 0 and 21<br>|
| Experimental: H5N1 Formulation 3 Group<br>Subjects in this group received 2 doses of H5N1 adjuvanted formulation 3 vaccine at a 21-day interval | Biological: Influenza Monovalent Whole virus (H5N1) adjuvanted vaccine<br>* 2 doses administered intramuscularly at the deltoid region of the non-dominant arm at Days 0 and 21<br>|
| Experimental: H5N1 Formulation 4 Group<br>Subjects in this group received 2 doses of H5N1 adjuvanted formulation 4 vaccine at a 21-day interval | Biological: Influenza Monovalent Whole virus (H5N1) adjuvanted vaccine<br>* 2 doses administered intramuscularly at the deltoid region of the non-dominant arm at Days 0 and 21<br>|
| Active Comparator: H5N1 Formulation 5 Group<br>Subjects in this group received 2 doses of H5N1 formulation 5 vaccine at a 21-day interval | Biological: Influenza Monovalent Whole virus (H5N1)<br>* 2 doses administered intramuscularly at the deltoid region of the non-dominant arm at Days 0 and 21<br>|
| Active Comparator: H5N1 Formulation 6 Group<br>Subjects in this group received 2 doses of H5N1 formulation 6 vaccine at a 21-day interval | Biological: Influenza Monovalent Whole virus (H5N1)<br>* 2 doses administered intramuscularly at the deltoid region of the non-dominant arm at Days 0 and 21<br>|
| Active Comparator: H5N1 Formulation 7 Group<br>Subjects in this group received 2 doses of H5N1 formulation 7 vaccine at a 21-day interval | Biological: Influenza Monovalent Whole virus (H5N1)<br>* 2 doses administered intramuscularly at the deltoid region of the non-dominant arm at Days 0 and 21<br>|
| Active Comparator: H5N1 Formulation 8 Group<br>Subjects in this group received 2 doses of H5N1 formulation 8 vaccine at a 21-day interval | Biological: Influenza Monovalent Whole virus (H5N1)<br>* 2 doses administered intramuscularly at the deltoid region of the non-dominant arm at Days 0 and 21<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the humoral immune response induced by the study vaccines in term of anti-haemagglutinin antibody titers | Geometric mean titers (GMTs) of serum antibodies | At Days 0, 21, 42 and 180 | 
| To evaluate the humoral immune response induced by the study vaccines in terms of seroconversion rates (SCRs), Conversion factors and protection rates to H5N1 virus |  | At days 21, 42 and 180 | 
| Occurrence of solicited local and general adverse events |  | During a 7 day follow-up period (i.e. day of vaccination and 6 subsequent days) after each dose of vaccine and overall | 
| Occurrence of unsolicited adverse events |  | During a 21 day follow-up period after the first vaccination and 30 day follow-up period after the second vaccination | 
| Occurrence of serious adverse events |  | During the entire study (Days 0 to 180) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the humoral immune response induced by the study vaccines in term of serum neutralizing antibody titers | Geometric mean titers (GMTs) of serum antibodies | At Days 0, 21, 42 and 180 | 
| To evaluate the cell-mediated immune response induced by the study vaccines in term of frequency of influenza-specific CD4/CD8 T lymphocytes |  | At days 0, 21, 42 and 180 | 
| To evaluate the humoral immune response induced by the study vaccines in terms of SCR for serum neutralizing antibody titers |  | At Days 21, 42 and 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prophylaxis of pandemic influenza