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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00800670
Other study ID # REB 09-001
Secondary ID
Status Terminated
Phase Phase 1
First received December 1, 2008
Last updated September 5, 2017
Start date June 2009
Est. completion date July 2013

Study information

Verified date September 2017
Source McMaster University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 24
Est. completion date July 2013
Est. primary completion date December 2012
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 55 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Ad5Ag85A
Single intra-muscular administration of 10^8 pfu of recombinant-deficient human adenoviral TB vaccine (Ad5Ag85A)
Ad5Ag85A
Single intra-muscular administration of 10^9 recombinant-deficient human adenoviral TB vaccine (Ad5Ag85A)

Locations

Country Name City State
Canada McMaster University Medical Centre Hamilton Ontario

Sponsors (1)

Lead Sponsor Collaborator
McMaster University

Country where clinical trial is conducted

Canada, 

References & Publications (2)

Jeyanathan M, Damjanovic D, Yao Y, Bramson J, Smaill F, Xing Z. Induction of an Immune-Protective T-Cell Repertoire With Diverse Genetic Coverage by a Novel Viral-Vectored Tuberculosis Vaccine in Humans. J Infect Dis. 2016 Dec 15;214(12):1996-2005. Epub 2 — View Citation

Smaill F, Jeyanathan M, Smieja M, Medina MF, Thanthrige-Don N, Zganiacz A, Yin C, Heriazon A, Damjanovic D, Puri L, Hamid J, Xie F, Foley R, Bramson J, Gauldie J, Xing Z. A human type 5 adenovirus-based tuberculosis vaccine induces robust T cell responses — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Local and systemic signs and symptoms and laboratory toxicity 24 weeks
Secondary 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 24 weeks
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