A/H5N1 Dose Ranging Study With Adjuvant Patch

Study Overview
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Brief Summary
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This is a Phase 1/2, randomized, observer-blind, placebo-controlled clinical trial. A maximum of 500 eligible subjects in 10 groups will be enrolled, randomized and vaccinated in this study. Subjects will receive an intramuscular injection of either the influenza A/H5N1 (low, medium or high dose) or placebo on Day 0 and Day 21 with or without a patch. This study will be performed in two parts. In Part 1, an initial safety evaluation will be performed in 100 randomized subjects. A Safety Review Committee (SRC)will review all safety data, including laboratory values, through the Day 7 visit, and compare those data against Stopping Criteria. If the treatments are considered safe, Part 2 of the study will be initiated and a second vaccination will be administered to subjects in Part 1 on Day 21. In Part 2, the remaining 400 subjects will be randomized, treated, and will follow the same visit structure and protocol-defined requirements as subjects in Part 1, without the additional laboratory safety measurements. An SRC review will also be performed of all safety data through the Day 28 visit for subjects participating in Part 1.

Official Title
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A Randomized, Observer-Blind, Placebo-Controlled Study to Assess the Safety and Immunogenicity of Intramuscular Inactivated Influenza A/H5N1 Vaccine Administered With and Without an Adjuvant Patch in Healthy Adults

Conditions
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Pandemic Influenza

Intervention / Treatment
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* Biological: A/H5N1
* Biological: A/H5N1
* Biological: A/H5N1
* Biological: A/H5N1
* Biological: A/H5N1
* Biological: A/H5N1
* Biological: A/H5N1
* Biological: A/H5N1
* Biological: A/H5N1
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult males or females 18-49 years of age (inclusive) Signed Informed Consent Women who are not post-menopausal or surgically sterile must have a negative serum or urine pregnancy test at screening and within 24 hours of each vaccination with understanding (through Informed Consent process) to not become pregnant and to employ an effective form of birth control for the duration of the study. Acceptable forms of birth control are: abstinence, hormonal contraceptives (oral, injectable, implant, patch, ring), double-barrier contraceptives (condom or diaphragm, with spermicide), and IUD Exclusion Criteria: Laboratory abnormalities [as determined by the Toxicity Grading Scale (grade 1 4)] at laboratory screening Abnormalities at physical examination [as determined by the Toxicity Grading Scale (grade 1-4)] Known allergies to any component of the vaccine Known egg protein allergy Known allergies to adhesives Known disturbance of coagulation Participated in research involving investigational product within 45 days before planned date of first vaccination Donated or received blood or blood products such as plasma within the past 45 days Received any licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to planned date of first vaccination Ever received investigational enterotoxigenic E. coli, LT, or LT (R192G) or NasalFlu, Berna Biotech, Ltd Ever received cholera toxin or vaccine (e.g. Orochol™, Dukoral™) History of travelers' diarrhea in the last two years History of abdominal surgery (excluding C-section, hysterectomy, cosmetic surgery, liposuction, appendectomy, cholecystectomy, ventral hernia repair, and other surgeries not pertaining to gastrointestinal problems) or history of, or recent acute gastrointestinal illness Previous vaccination with a pandemic candidate vaccine or previous proven contact with A/H5N1 wild type virus (contact with an individual with laboratory-confirmed A/H5N1 infection or contact with an animal which died as a result of A/H5N1 infection) Recent or regular use of oral, topical or injected steroid medications within 45 days prior to first vaccination Use of immunosuppressive systemic steroid medications including inhaled steroids within three months prior to first vaccination Comorbid conditions or treatments that are immunosuppressive, including cancer, diabetes, end-stage renal disease, as determined by the Investigator Positive serology for HIV-1, HIV-2, HBsAg, or HCV History of severe atopy Medical history of acute or chronic skin disease at vaccination area(s) Active skin allergy Signs of acute skin infection, sunburn or skin abnormalities at the vaccination area(s) including fungal infections, severe acne, or active contact dermatitis, or a history of keloid formation Hirsute (significant amount of hair) at vaccination area(s) Artificial tanning (UV radiation) over the duration of the study including the screening period Visible tattoos or marks (tattoos/scars) at the vaccination area(s) that would prevent appropriate dermatologic monitoring of the vaccination site(s) Fever greater than or equal to 38.0°C (100.4°F) at the time of planned vaccination Suspicion of or recent history of (within one year of planned vaccination) alcohol or substance abuse Women who are pregnant or breastfeeding Acute illness at screening or at baseline Ever had a serious reaction to prior influenza vaccination Developed a neurological disorder (such as Guillain Barré syndrome) in the six weeks following a previous influenza vaccination Medical history of achlorhydria Employee of the investigational site History of employment in bird or poultry industries or considerable exposure to birds (e.g. poultry or bird veterinarians, bird breeders, poultry butchers and/or cullers, etc.)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br> | Biological: A/H5N1<br>* Low dose A/H5N1 (0.5mL); Route IM - Day 0 and Day 21; No LT Patch Day 0 or Day 21<br>|
| Experimental: Group 2<br> | Biological: A/H5N1<br>* Low dose A/H5N1 (0.5mL); Route IM - Day 0 and Day 21; no LT patch on Day 0; LT Patch on Day 21<br>|
| Experimental: Group 3<br> | Biological: A/H5N1<br>* Low dose A/H5N1 (0.5mL); Route IM - Day 0 and Day 21; LT patch on Day 0 and Day 21<br>|
| Experimental: Group 4<br> | Biological: A/H5N1<br>* Medium dose A/H5N1 (0.5mL); Route IM - Day 0 and Day 21; no LT patch on Day 0 or Day 21<br>|
| Experimental: Group 5<br> | Biological: A/H5N1<br>* Medium dose A/H5N1 (0.5mL); Route IM - Day 0 and Day 21; no LT patch on Day 0; LT Patch on Day 21<br>|
| Experimental: Group 6<br> | Biological: A/H5N1<br>* Medium dose A/H5N1 (0.5mL); Route IM - Day 0 and Day 21; LT patch on Day 0 and Day 21<br>|
| Experimental: Group 7<br> | Biological: A/H5N1<br>* High dose A/H5N1 (0.5mL); Route IM - Day 0 and Day 21; no LT patch on Day 0 or Day 21<br>|
| Experimental: Group 8<br> | Biological: A/H5N1<br>* High dose A/H5N1 (0.5mL); Route IM - Day 0 and Day 21; no LT patch on Day 0; LT Patch on Day 21<br>|
| Experimental: Group 9<br> | Biological: A/H5N1<br>* High dose A/H5N1 (0.5mL); Route IM - Day 0 and Day 21; LT patch on Day 0 and Day 21<br>|
| Placebo Comparator: Group 10<br> | Biological: Placebo<br>* Placebo (0.5ml); Route IM - Day 0 and Day 21; no LT patch on Day 0 or Day 21<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Intramuscular A/H5N1 with and without the LT adjuvant patch |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstration of adjuvant effect and evaluation of immunogenicity |  | Day 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Avian, Pandemic, Influenza, A/H5N1