Study of the Safety and Immunogenicity of an Adenovirus-Based Tuberculosis Vaccine - Full Text View

Sponsored by:	McMaster University
Information provided by:	McMaster University
ClinicalTrials.gov Identifier:	NCT00800670

Purpose

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.

Condition	Intervention	Phase
Tuberculosis	Biological: Ad5Ag85A	Phase I

MedlinePlus related topics: Tuberculosis

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Open Label, Dose Comparison, Single Group Assignment, Safety Study
Official Title:	Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of an Adenovirus-Based Tuberculosis Vaccine

Further study details as provided by McMaster University:

Primary Outcome Measures:

Local and systemic signs and symptoms and laboratory toxicity [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	48
Study Start Date:	March 2009

Arms	Assigned Interventions
Lower dose: Experimental Lower dose of Ad5Ag85A: 10^8pfu	Biological: Ad5Ag85A Single intra-muscular administration of 10^8 pfu of recombinant-deficient human adenoviral TB vaccine (Ad5Ag85A)
Higher dose: Experimental Higher dose of vaccine Ad5Ag85A: 10^9pfu	Biological: Ad5Ag85A Single intra-muscular administration of 10^9 recombinant-deficient human adenoviral TB vaccine (Ad5Ag85A)

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy human subjects who are between 18 and 55 years of age with or without a history of BCG vaccination.
HIV antibody negative
For women, negative pregnancy test and practising two acceptable forms of contraception for the duration of the study (barrier contraceptive, birth control pill, surgically sterile, post-menopausal 2yrs, abstinence)
For men, using barrier contraception for the duration of the study

Exclusion Criteria:

Pregnant or lactating women
Subjects who have any acute or chronic illnesses including active tuberculosis or receiving any drug treatment in the opinion of the investigator likely to affect the immune system.
Subjects with symptoms suggestive of an upper respiratory tract infection (including cough, runny nose, or sore throat)
Subjects who have a history of active or latent TB infection or whose PBMCs are strongly responsive to ESAT6/CFP10 stimulation using a commercial interferon gamma release assay for TB [consistent with latent TB infection].
Subjects who have laboratory values outside the normal range.
Not available for scheduled follow-up visits. Subjects enrolled in the trial must be followed at 7 days, and then at 2, 4, 8, 16 and 24 weeks post-vaccination.
Failure to provide written consent.
Known allergy to vaccine components
Known exposure to active TB within past 6 months or subjects whose occupation puts them at increased risk of TB exposure (based on Hamilton Health Science/St Joseph Healthcare list of high risk personnel)
Any abnormality on chest x-ray suggestive of active or remote tuberculosis infection.
PPD skin test within last 12 months
BCG status unknown

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00800670

Contacts

Contact: Fiona M Smaill, MD	905-521-2100 ext 76332	smaill@mcmaster.ca
Contact: Marek Smieja, MD	905-522-1155 ext 5140	smiejam@mcmaster.ca

Locations

Canada, Ontario
McMaster University Medical Centre
Hamilton, Ontario, Canada, L8N 3Z5

Sponsors and Collaborators

McMaster University

Investigators

Principal Investigator:	Zhou Xing, PhD	McMaster University
Principal Investigator:	Fiona M Smaill, MD	McMaster University

More Information

Responsible Party:	McMaster University ( Dr Fiona Smaill )
Study ID Numbers:	REB 09-001
Study First Received:	December 1, 2008
Last Updated:	December 17, 2008
ClinicalTrials.gov Identifier:	NCT00800670
Health Authority:	Canada: Health Canada

Keywords provided by McMaster University:

tuberculosis
vaccine
adenovirus

Study placed in the following topic categories:

Bacterial Infections
Gram-Positive Bacterial Infections
Adenoviridae Infections
Mycobacterium Infections
Tuberculosis

Additional relevant MeSH terms:

Actinomycetales Infections

ClinicalTrials.gov processed this record on January 16, 2009