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

Sponsor

Emergent BioSolutions (Industry)

Overall Status

Completed

CT.gov ID

NCT01006798

Collaborator

(none)

166

Enrollment

Locations

Arms

Duration (Months)

41.5

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Bird Flu Influenza	Other: Placebo Biological: Ad4-H5-Vtn Biological: Sanofi Pasteur Influenza Virus Vaccine, H5N1	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

166 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Sep 1, 2011

Actual Study Completion Date :

Sep 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Kentucky	Lexington	Kentucky	United States	40536
2	The Center for Pharmaceutical Research	Kansas City	Missouri	United States	64114
3	University of Rochester	Rochester	New York	United States	14642
4	Coastal Carolina Research Center, Inc.	Mount Pleasant	South Carolina	United States	29464