Study of the Safety and Immunogenicity of an Adenovirus-based Tuberculosis Vaccine
The purpose of this Phase 1 study is to evaluate the safety and immune responses of a new tuberculosis vaccine, Ad5Ag85A, administered to healthy volunteers. 48 subjects will be recruited, 24 who have previously been vaccinated with BCG and 24 who have not received BCG vaccine. Two doses of the vaccine will be compared.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of an Adenovirus-based Tuberculosis Vaccine|
- Local and systemic signs and symptoms and laboratory toxicity [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
- Immunogenicity will be compared among the groups by determining the level and quantity of antigen-specific T cells by human interferon ELISA and Elispot assay [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||June 2009|
|Study Completion Date:||July 2013|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Experimental: Lower dose
Lower dose of Ad5Ag85A: 10^8pfu
Single intra-muscular administration of 10^8 pfu of recombinant-deficient human adenoviral TB vaccine (Ad5Ag85A)
Experimental: Higher dose
Higher dose of vaccine Ad5Ag85A: 10^9pfu
Single intra-muscular administration of 10^9 recombinant-deficient human adenoviral TB vaccine (Ad5Ag85A)
As the global tuberculosis (TB) epidemic continues, the incidence of latent and active TB is expected to rise. HIV-infected persons are especially susceptible to TB. An improved TB vaccine over the present BCG vaccine is needed.
The general objectives of our TB vaccine research program are to develop a safe and effective vaccine for persons who at increased risk of contracting TB or reactivating latent tuberculosis and develop a safe booster vaccine for persons who have been previously vaccinated with BCG.
This is an open-labeled phase 1 single institution trial investigating a recombinant genetic TB vaccine AdAg85A given by intramuscular injection in healthy subjects with or without a history of BCG vaccination. Ad5Ag85A is a recombinant replication-deficient adenoviral vector expressing an M. tuberculosis immunogenic antigen Ag85A. We have shown that it is safe, immunogenic and associated with enhanced protection against challenge with virulent M Tb in murine, bovine and guinea pig models. Clinical grade AdAg85A has been manufactured by the Robert E Fitzhenry Vector Laboratory, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.
The effect of pre-existing adenovirus antibodies on the safety and immunogenicity of the recombinant AdTB vaccine will be evaluated and the results of the PPD skin test following vaccination evaluated in a subset of subjects with a history of a negative PPD skin test.
|McMaster University Medical Centre|
|Hamilton, Ontario, Canada, L8N 3Z5|
|Principal Investigator:||Zhou Xing, PhD||McMaster University|
|Principal Investigator:||Fiona M Smaill, MD||McMaster University|