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

Primary Purpose

Tuberculosis

Status

Terminated

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

Ad5Ag85A

About this trial

This is an interventional prevention trial for Tuberculosis focused on measuring tuberculosis, vaccine, adenovirus

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

McMaster University Medical Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Lower dose

Higher dose

Arm Description

Lower dose of Ad5Ag85A: 10^8pfu

Higher dose of vaccine Ad5Ag85A: 10^9pfu

Outcomes

Primary Outcome Measures

Local and systemic signs and symptoms and laboratory toxicity

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

Full Information

NCT ID

NCT00800670

First Posted

December 1, 2008

Last Updated

September 5, 2017

Sponsor

McMaster University

1. Study Identification

Unique Protocol Identification Number

NCT00800670

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2017

Overall Recruitment Status

Terminated

Why Stopped

Study was terminated after the low dose cohort had been enrolled

Study Start Date

June 2009 (undefined)

Primary Completion Date

December 2012 (Actual)

Study Completion Date

July 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

McMaster University

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberculosis

Keywords

tuberculosis, vaccine, adenovirus

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lower dose

Arm Type

Experimental

Arm Description

Lower dose of Ad5Ag85A: 10^8pfu

Arm Title

Higher dose

Arm Type

Experimental

Arm Description

Higher dose of vaccine Ad5Ag85A: 10^9pfu

Intervention Type

Biological

Intervention Name(s)

Ad5Ag85A

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Ad5Ag85A

Intervention Description

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

Primary Outcome Measure Information:

Title

Local and systemic signs and symptoms and laboratory toxicity

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhou Xing, PhD

Organizational Affiliation

McMaster University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Fiona M Smaill, MD

Organizational Affiliation

McMaster University

Official's Role

Principal Investigator

Facility Information:

Facility Name

McMaster University Medical Centre

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L8N 3Z5

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

24089406

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 in humans despite preexisting anti-adenovirus immunity. Sci Transl Med. 2013 Oct 2;5(205):205ra134. doi: 10.1126/scitranslmed.3006843.

Results Reference

result

PubMed Identifier

27703038

Citation

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. doi: 10.1093/infdis/jiw467. Epub 2016 Oct 4.

Results Reference

result

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

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