Influenza A/H5N1 Vaccine Clinical Trial (IVACFLU-A/H5N1) - Phase 1

Study Overview
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Brief Summary
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This is a first-in-human study of safety and immunogenicity of an A/H5N1 inactivated whole cell vaccine when given in two injections in two doses (low and high) compared to a placebo in 76 healthy adult subjects in Vietnam. Vaccine and placebo are manufactured by the IVAC in Vietnam.

Detailed Description
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This is a phase 1, double blinded, randomized, placebo-controlled study. Seventy-six healthy male and female adults, 18 to 30 years of age, will be enrolled into the trial. Subjects will be randomized to one of three treatment allocations: 32 subjects to 7.5 mcg/dose vaccine (low dose), 32 subjects to 15 mcg/dose vaccine (high dose) and 12 subjects to placebo. This sample size was selected to enable at least 30 evaluable subjects in each of the groups receiving active vaccine. The study will utilize a block randomization to assure a balance of 8:8:3 vaccine and placebo when all subjects are enrolled. The study will be double blinded, meaning the study subjects, investigators, and the sponsor will be unaware of the treatment allocated to each subject until the clinical trial database is declared final and locked. Since this is a first-in-human study, all injections of study product will be sequential and staggered and there will be a safety evaluation between a sentinel cohort of 19 subjects and the remaining 57 study subjects for both the 1st and 2nd doses in the study. A sentinel group of 19 participants' enrollment and vaccination will precede the remainder of the study group by approximately 2-3 weeks. Product administration for both injections of vaccine or placebo will be sequential and staggered.

Official Title
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A Phase 1 Double Blinded, Randomized, Placebo-Controlled Study to Examine the Safety and Immunogenicity of an Inactivated A/H5N1 Influenza Vaccine (IVACFLU-A/H5N1) Produced by IVAC in Healthy Adult Volunteers in Vietnam

Conditions
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Influenza A Subtype H5N1 Infection

Intervention / Treatment
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* Biological: IVACFLU-A/H5N1, 7.5 mcg
* Biological: IVACFLU-A/H5N1, 15 mcg
* Other: Placebo Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adult 18 through 30 years of age at the enrollment visit. Literate and willing to provide written informed consent. Healthy adults, as established by the medical history and screening evaluations, including physical examination. Capable and willing to complete diary cards and willing to return for all follow-up visits. For females, willing to utilize reliable birth control measures (intrauterine device, hormonal contraception, condoms) through the Day 42 visit Exclusion Criteria: Participation in another clinical trial involving any therapy within the previous three months or planned enrollment in such a trial during the period of this study. Receipt of any non-study vaccine within four weeks prior to enrollment or refusal to postpone receipt of such vaccines until after the Day 42 visit. Current or recent (within two weeks of enrollment) acute illness with or without fever. Receipt of immune globulin or other blood products within three months prior to study enrollment or planned receipt of such products prior to the Day 42 visit. Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants or other immune-modulating therapy within six months prior to study enrollment. (For corticosteroids, this means prednisone or equivalent, ≥ 0.5 mg per kg per day; topical steroids are allowed.) History of asthma. Hypersensitivity after previous administration of any vaccine. Other AE following immunization, at least possibly related to previous receipt of any vaccine. Suspected or known hypersensitivity to any of the study vaccine components, including chicken or egg protein. Known hypersensitivities (allergies) to food or the natural environment. Acute or chronic clinically significant pulmonary, cardiovascular, hepatobiliary, metabolic, neurologic, psychiatric or renal functional abnormality, as determined by medical history, physical examination or clinical laboratory screening tests, which in the opinion of the investigator, might interfere with the study objectives. History of any blood or solid organ cancer. History of thrombocytopenic purpura or known bleeding disorder. History of seizures. Known or suspected immunosuppressed or immunodeficient condition of any kind. Known chronic HBV or HCV infection. Known active tuberculosis or symptoms of active tuberculosis, regardless of cause. History of chronic alcohol abuse and/or illegal drug use. Pregnancy or lactation. (A negative pregnancy test will be required before administration of study product for all women of childbearing potential.) History of Guillain-Barré Syndrome Any condition that, in the opinion of the investigator, would increase the health risk to the subject if he/she participates in the study or would interfere with the evaluation of the study objectives.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 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: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IVACFLU-A/H5N1, 7.5 mcg<br>IVACFLU-A/H5N1, 7.5 mcg HA per dose | Biological: IVACFLU-A/H5N1, 7.5 mcg<br>* Contains 7.5 mcg HA and 0.6 mg of aluminum hydroxide adjuvant per 0.5 mL dose.<br>|
| Experimental: IVACFLU-A/H5N1, 15 mcg<br>IVACFLU-A/H5N1, 15 mcg HA per dose. | Biological: IVACFLU-A/H5N1, 15 mcg<br>* Contains 15 mcg HA and 0.6 mg of aluminum hydroxide adjuvant per 0.5 mL dose<br>|
| Placebo Comparator: Placebo<br>Phosphate buffered saline | Other: Placebo Comparator<br>* PBS, pH 7.2 in 0.5 mL single-dose vials.<br>* Other names: Phosphate Buffered Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immediate Reactions Occurring Within 60 Minutes of Administration of Any Dose | Data presented are after 1st and 2nd vaccination combined. All participants were observed for immediate reactions for 60 minutes after administration of study product, with appropriate medical treatment readily available in case of an anaphylactic reaction following the administration of study product. | 60 min post injection | 
| Number of Participants With at Least One Solicted Reactogenicity After Both Injections | Data presented are after 1st and 2nd vaccination combined. Solicted reactogenicity are local and systemic events that are expected after injection and specifically asked of the participant. Only reported reactogenicity is presented. If not shown, then no participant reported that reaction in any study group. Local reactions are redness, swelling, pain, tenderness, and hardness. Systemic reactions are actual and subjective fever, chills, cough, difficulty breathing, runny nose, nasal congestion, sore throat, hoarseness of voice, headache, confusion. convulsions/seizures, fatigue/malaise, muscle aches (generalized), joint pain, pink or red eyes, sore eyes, itchy eyes, drainage from eyes. ear pain or discharge, rash, abdominal pain, diarrhea, vomiting, and jaundice. | Within 7 days after injection | 
| Number of Participants With at Least One Unsolicited AE | Summary of number of participants with at least one unsolicited AE after 1st and 2nd vaccination combined. Please see the adverse event section of this report for full details. | Within 7 weeks of injection | 
| All Serious Adverse Events (SAEs) Occurring Within 3 Weeks of Receipt of Any Dose | Summary data. Data presented are after 1st and 2nd injections combined. Please see AE reporting section of this report for full details. | Within 3 weeks of any injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Subjects Achieving a Hemagglutination Inhibition (HAI) Titer ≥ 1:40 Pre-vaccination (Day 0) to Post 2nd Vaccination (Day 49) |  | Day 0 to Day 49 | 
| The Proportion of Subjects Achieving a Four-fold Rise in HAI Between Doses or From Baseline to Post-Injection 2 |  | Days 21 and 42 | 
| Geometric Mean Titer (GMT) of Hemagglutination Inhibition After Each Dose |  | Days 0, 21 and 42 | 
| Geometric Mean Titer (GMT) of Neutralizing Antibody After Each Dose |  | Days 0, 21, and 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Avian, H5N1, Vaccine