Safety and Immunogenicity of Replication-Competent Adenovirus 4-vectored Vaccine for Avian Influenza H5N1

Study Overview
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Brief Summary
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The purpose of this study is to compare the safety and immunogenicity over a 9-month period of five different dosages of Ad4-H5-Vtn in volunteers (Vaccinees) who receive three doses of the study vaccine or placebo. In addition, transmission of Ad4-H5-Vtn will be evaluated in all Household Contacts residing with the vaccinated volunteers. Vaccinees also may participate in a substudy in which they receive a booster vaccination with the licensed Influenza Virus Vaccine, H5N1 (Sanofi Pasteur).

Detailed Description
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At least 160 healthy Vaccinees will be randomized into 5 ascending dosage cohorts each consisting of at least 32 volunteers. In each dosage cohort Vaccinees will be randomly assigned to receive 3 doses of either Ad4-H5-Vtn or placebo separated by approximately 56 days. Volunteers will be followed for 168 days post-third vaccination.

Official Title
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Phase 1 Evaluation of the Safety and Immunogenicity of a Replication-Competent Adenovirus Serotype 4-vectored H5N1 Influenza Candidate Vaccine - Ad4-H5-Vtn

Conditions
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Bird Flu, Influenza

Intervention / Treatment
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* Other: Placebo
* Biological: Ad4-H5-Vtn
* Biological: Sanofi Pasteur Influenza Virus Vaccine, H5N1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults and their healthy adult household contacts. Exclusion Criteria: Healthcare workers who have direct contact with patients who are immunodeficient, are HIV-positive, have an unstable medical condition, or are under the age of 18. Childcare workers who have direct contact with children 5 years old and younger. Resides with Household Contacts who are under the age of 18 or over the age of 65. Received or plans to receive licensed inactivated 2009 H1N1 influenza vaccine from 14 days prior to 14 days after any study vaccination. Received or plans to receive any other licensed vaccines from 30 days prior to the first study vaccination until 30 days after the third study vaccination.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>three vaccinations of 10^7vp Ad4-H5-Vtn or placebo | Other: Placebo<br>* enteric coated capsule containing no vaccine virus<br>* Other names: Placebo for Ad4-H5-Vtn;Biological: Ad4-H5-Vtn<br>* a live, replication-competent, recombinant Ad4 virus expressing the HA of H5N1 influenza (A/Vietnam/1194/2004) in an enteric capsule for oral administration<br>* Other names: Adenovirus Serotype 4-vectored H5N1 Influenza Vaccine;Biological: Sanofi Pasteur Influenza Virus Vaccine, H5N1<br>* Single administration of a heterologous boost given to volunteers 3 to 15 months following their last vaccination with Ad4-H5-Vtn or placebo.<br>* Other names: licensed H5N1 vaccine;|
| Experimental: Cohort 2<br>three vaccinations of the 10^8vp Ad4-H5-Vtn or placebo | Other: Placebo<br>* enteric coated capsule containing no vaccine virus<br>* Other names: Placebo for Ad4-H5-Vtn;Biological: Ad4-H5-Vtn<br>* a live, replication-competent, recombinant Ad4 virus expressing the HA of H5N1 influenza (A/Vietnam/1194/2004) in an enteric capsule for oral administration<br>* Other names: Adenovirus Serotype 4-vectored H5N1 Influenza Vaccine;Biological: Sanofi Pasteur Influenza Virus Vaccine, H5N1<br>* Single administration of a heterologous boost given to volunteers 3 to 15 months following their last vaccination with Ad4-H5-Vtn or placebo.<br>* Other names: licensed H5N1 vaccine;|
| Experimental: Cohort 3<br>three vaccinations of 10^9 Ad4-H5-Vtn or placebo | Other: Placebo<br>* enteric coated capsule containing no vaccine virus<br>* Other names: Placebo for Ad4-H5-Vtn;Biological: Ad4-H5-Vtn<br>* a live, replication-competent, recombinant Ad4 virus expressing the HA of H5N1 influenza (A/Vietnam/1194/2004) in an enteric capsule for oral administration<br>* Other names: Adenovirus Serotype 4-vectored H5N1 Influenza Vaccine;Biological: Sanofi Pasteur Influenza Virus Vaccine, H5N1<br>* Single administration of a heterologous boost given to volunteers 3 to 15 months following their last vaccination with Ad4-H5-Vtn or placebo.<br>* Other names: licensed H5N1 vaccine;|
| Experimental: Cohort 4<br>three vaccinations of 10^10 Ad4-H5-Vtn or placebo | Other: Placebo<br>* enteric coated capsule containing no vaccine virus<br>* Other names: Placebo for Ad4-H5-Vtn;Biological: Ad4-H5-Vtn<br>* a live, replication-competent, recombinant Ad4 virus expressing the HA of H5N1 influenza (A/Vietnam/1194/2004) in an enteric capsule for oral administration<br>* Other names: Adenovirus Serotype 4-vectored H5N1 Influenza Vaccine;Biological: Sanofi Pasteur Influenza Virus Vaccine, H5N1<br>* Single administration of a heterologous boost given to volunteers 3 to 15 months following their last vaccination with Ad4-H5-Vtn or placebo.<br>* Other names: licensed H5N1 vaccine;|
| Experimental: Cohort 5<br>three vaccinations of 10^11 Ad4-H5-Vtn or placebo | Other: Placebo<br>* enteric coated capsule containing no vaccine virus<br>* Other names: Placebo for Ad4-H5-Vtn;Biological: Ad4-H5-Vtn<br>* a live, replication-competent, recombinant Ad4 virus expressing the HA of H5N1 influenza (A/Vietnam/1194/2004) in an enteric capsule for oral administration<br>* Other names: Adenovirus Serotype 4-vectored H5N1 Influenza Vaccine;Biological: Sanofi Pasteur Influenza Virus Vaccine, H5N1<br>* Single administration of a heterologous boost given to volunteers 3 to 15 months following their last vaccination with Ad4-H5-Vtn or placebo.<br>* Other names: licensed H5N1 vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, defined as the frequency and severity of vaccine-related reactogenicity events and reported AEs |  | Throughout trial (reactogenicity for 7 days following each vaccination) | 
| Immunogenicity (humoral) defined by H5 HAI titer |  | At all available timepoints | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity (humoral), defined by Ad4 antibody response |  | At all available timepoints | 
| Replication/excretion of Ad4-H5-Vtn virus |  | Throughout trial | 
| Transmission to household contacts as measured by AE assessment and antibody response and viral replication/excretion |  | Throughout trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Virus Diseases, Respiratory Tract Diseases, Vaccine