Study of the Safety and Immunogenicity of an Adenovirus-based Tuberculosis Vaccine
|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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00800670
|McMaster University Medical Centre|
|Hamilton, Ontario, Canada, L8N 3Z5|
|Principal Investigator:||Zhou Xing, PhD||McMaster University|
|Principal Investigator:||Fiona M Smaill, MD||McMaster University|