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

Tuberculosis Clinical Trial

Official title:

Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of an Adenovirus-based Tuberculosis Vaccine

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00800670
• Other study ID #: REB 09-001
• 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
• 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

Related Conditions & MeSH terms

• Adenoviridae Infections
• Tuberculosis

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