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

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 1


Study Type:	Interventional
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

Resource links provided by NLM:

MedlinePlus related topics: Tuberculosis

Genetic and Rare Diseases Information Center resources: Tuberculosis

U.S. FDA Resources

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:	June 2009
Study Completion Date:	July 2013
Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lower dose Lower dose of Ad5Ag85A: 10^8pfu	Biological: Ad5Ag85A 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	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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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

No publications provided


Responsible Party:	Fiona Smaill, Professor and Chair, McMaster University
ClinicalTrials.gov Identifier:	NCT00800670 History of Changes
Other Study ID Numbers:	REB 09-001
Study First Received:	December 1, 2008
Last Updated:	August 6, 2013
Health Authority:	Canada: Health Canada

Keywords provided by McMaster University:


tuberculosis vaccine adenovirus

Additional relevant MeSH terms:


Tuberculosis Actinomycetales Infections Bacterial Infections Gram-Positive Bacterial Infections Mycobacterium Infections

ClinicalTrials.gov processed this record on February 27, 2015