Open-label Study to Assess Immunogenicity and Safety of a Vaccine Enhancement Patch When Administered With 2 Doses of H5N1 Vaccine

Study Overview
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Brief Summary
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Groups 1 to 3 will receive two vaccinations on Day 0 and Day 21. Group 1 will receive 3.8µg A/H5N1 antigen formulated with AS03 adjuvant, administered by IM injection. Group 2 will receive 15µg A/H5N1 by IM alone. Group 3 will also receive 15µg A/H5N1 antigen administered IM but followed by the topical application of a VEP at the vaccination site. Group 4 will receive a single vaccination on Day 0 of 30µg A/H5N1antigen by IM, followed by application of a VEP at the vaccination site. The VEP (Vaccine Enhancement Patch) contains 50 mcg LT (heat-labile enterotoxin of E. coli)

Official Title
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A Phase 1/2, Randomized, Open-Label, Study to Assess the Immunogenicity and Safety of a Vaccine Enhancement Patch (VEP) When Administered With Two Doses of Intramuscular Inactivated Influenza H5N1 Vaccine in Healthy Adults

Conditions
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Healthy

Intervention / Treatment
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* Biological: A/H5N1 Antigen
* Drug: Vaccine Enhancement Patch


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 at all in-clinic visits with understanding to not become pregnant over the duration of the study. Exclusion Criteria: Clinically significant laboratory abnormalities at screening abnormalities at physical examination known allergies to any component of the A/H5N1 antigen known egg protein allergy known allergies to adhesives known coagulation disorders use of any anticoagulant medication within 30 days prior to vaccination or planned usage during the study period participated in research involving investigational product within 30 days before planned date of vaccination or planned participation during study period donated or received blood or blood products such as plasma within the three months before planned date of vaccination or planned donation or use during the study period received or planned receipt of seasonal influenza vaccine during the study period received any licensed vaccines within 2 weeks (inactivated vaccines) or 4 weeks (live vaccines) prior to planned date of vaccination planned receipt of any licensed vaccine during the first 42 days on study previous or planned vaccination with any vaccine containing an oil in water emulsion adjuvant previous or planned vaccination with pandemic vaccine against A/H5N1 or previous proven contact with A/H5N1 wild type virus ever received investigational enterotoxigenic E. coli LT, or LT (R192G) or NasalFlu, Berna Biotech, Ltd. Ever received cholera toxin or vaccine Recent or regular use of oral, topical or injected steroid medications within 30 days prior to vaccination or planned use during the study period. Use of immunosuppressive systemic steroid medications including inhaled steroids within three months prior to vaccination or planned use during the study period Comorbid conditions or treatments that are immunosuppressive, including cancer, diabetes, and 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 active skin allergy signs of acute skin infection, sunburn or skin abnormalities at the vaccination area including fungal infections, severe acne, active contact dermatitis, or a history of keloid formation hirsute at vaccination area artificial tanning over the duration of the study including the screening period visible tattoos or marks at the vaccination area that would prevent appropriate dermatologic monitoring of the vaccination site fever greater than or equal to 38.0°C at the time of planned vaccination suspicion of or recent history of alcohol or substance abuse women who are pregnant or breastfeeding acute illness at screening or at the time of planned vaccination ever had a serious reaction to prior influenza vaccination developed a neurological disorder following a previous influenza vaccination or have any acute and evolving neurological disorder employee of the investigational site or sponsor history of employment in bird or poultry industries or considerable exposure to birds

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>3.8 mcg with AS03 adjuvant at D0 and 21 | Biological: A/H5N1 Antigen<br>* A/H5N1 Antigen<br>|
| Experimental: Group 2<br>15 mcg at D0 and 21 | Biological: A/H5N1 Antigen<br>* A/H5N1 Antigen<br>|
| Experimental: Group 3<br>15 mcg + 50 mcg VEP at D0 and 21 | Biological: A/H5N1 Antigen<br>* A/H5N1 Antigen<br>Drug: Vaccine Enhancement Patch<br>* Vaccine Enhancement Patch<br>|
| Experimental: Group 4<br>30 mcg + 50 mcg VEP at D0 | Biological: A/H5N1 Antigen<br>* A/H5N1 Antigen<br>Drug: Vaccine Enhancement Patch<br>* Vaccine Enhancement Patch<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate hemagglutination inhibition (HI) immune responses | Evaluate hemagglutination inhibition (HI) immune responses to two doses of 15μg A/H5N1 achieved in the antigen plus VEP group versus the antigen alone group (Group 3 vs. Group 2) at Day 42 using standard serological parameters (Geometric Mean Titer [GMT], Geometric Mean Fold Ratio [GMFR], seroconversion and seroprotection). | Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of 15µg and 30µg IM A/H5N1 antigen administered with the 50µg VEP | Comprehensive assessment of solicited and non-solicited local (vaccination site) and systemic adverse events (AEs) Safety follow-up through six months after last vaccination | 8 months | 
| Characterize HI immune responses | Characterize HI immune responses in the 15µg A/H5N1 antigen alone group (Group 2) and the 15µg A/H5N1 antigen plus VEP group (Group 3) to determine if levels meet or exceed EMA CPMP/BWP/214/96 criteria for immunogenicity: The percent of subjects achieving seroconversion for HI antibody titer should meet or exceed 40% The percent of subjects achieving an HI antibody titer ≥ 1:40 should meet or exceed 70% GMT increase > 2.5 | 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity and Safety