Phase 1 Clinical Trial of the Safety and Immunogenicity of an Adenovirus-based TB Vaccine Administered by Aerosol

NCT ID: NCT02337270

Last Updated: 2021-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-05

Study Completion Date

2021-09-07

Brief Summary

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This is a phase 1 study, in healthy volunteers who have previously been immunized with bacilli Calmette Guerin (BCG), to evaluate the safety and immune responses that develop in the blood and lungs following the administration by aerosol of a new experimental adenovirus-based vaccine for tuberculosis (TB), Ad5Ag85A.

Detailed Description

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This is a phase 1, open label study to evaluate the safety and immunogenicity of a single administration of one of two doses of a recombinant replication deficient human adenoviral (Ad5) TB vaccine containing the immunodominant antigen Ag85A delivered to the respiratory tract by aerosol in healthy volunteers with a history of BCG immunization.

28 healthy volunteers will be enrolled. The first cohort (n=8) will receive a lower dose of vaccine using the AeroNeb Solo Vibrating Mesh Nebulizer. For the second cohort (n=20) participants will be randomized to either a higher dose of vaccine by aerosol (n=10) or intramuscular administration (n=10). Cellular immune responses in the lung and peripheral blood will be evaluated

Conditions

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Tuberculosis

Keywords

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Tuberculosis Vaccine Aerosol Adenovirus Immunogenicity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Group 1 Aerosol

Receive 10\^6 Ad5Ag85A by aerosol at day 0

Group Type EXPERIMENTAL

Ad5Ag85A

Intervention Type BIOLOGICAL

Aerosol administration of Ad5Ag85A

Group 2 Aerosol

Receive 2x10\^6 Ad5Ag85A by aerosol at day 0

Group Type EXPERIMENTAL

Ad5Ag85A

Intervention Type BIOLOGICAL

Aerosol administration of Ad5Ag85A

Group 3 Intramuscular

Receive 10\^8 Ad5Ag85A by intramuscular injection at day 0

Group Type EXPERIMENTAL

Ad5Ag85A

Intervention Type BIOLOGICAL

Aerosol administration of Ad5Ag85A

Interventions

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Ad5Ag85A

Aerosol administration of Ad5Ag85A

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Healthy human subjects who are between 18 and 55 years of age with a history of BCG vaccination.
2. HIV antibody negative
3. Able to understand and comply with protocol requirements and instructions; able to attend scheduled study visits and complete required investigations.
4. For women, negative pregnancy test and practicing two acceptable forms of contraception for the duration of the study (barrier contraceptive, birth control pill, surgically sterile, post-menopausal 2 years, abstinence)
5. For men, using barrier contraception for the duration of the study

Exclusion Criteria

1. Pregnant or lactating women
2. Subjects who have any acute or chronic illnesses including active tuberculosis, any relevant findings on physical examination or are receiving any drug treatment in the opinion of the investigator likely to affect the immune system including current use of inhaled or nasal steroids.
3. Subjects with a history of any bleeding disorder or receiving any drug treatment that in the opinion of the investigator may increase the risk of bleeding
4. Subjects with a history of respiratory disease, e.g. asthma, chronic bronchitis, chronic obstructive pulmonary disease (COPD).
5. Current smokers, including e-cigarettes, and ex-smokers who have quit within the last year, as reported by the subject
6. Subjects with clinically significant abnormality of baseline spirometry tests
7. Any health-related condition for which study bronchoscopy is contraindicated
8. Subjects who have a history of active or latent TB infection or whose PBMC's are responsive to ESAT6/CFP10 stimulation using a commercial interferon gamma release assay for TB \[consistent with latent TB infection\].
9. Subjects whose baseline laboratory values are outside of the normal range unless the abnormality is considered not to be of clinical relevance by the Investigator. A single repeat test is allowed during the screening period.
10. Subjects whose use of alcohol or drugs would, in the opinion of the investigator, interfere with adherence to the study protocol.
11. Subjects who are using, or have a history of using, inhaled cocaine, metamphetamine or other inhaled or smoked recreational drugs. Subjects who give a history of last smoking marijuana more than a year ago may be enrolled, as long as they do not smoke marijuana for the duration of the study.
12. Failure to provide written consent.
13. Known allergy to vaccine components
14. Previous vaccination with Ad5Ag85A or any other experimental TB vaccine
15. 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)
16. Any abnormality on chest x-ray suggestive of active or remote tuberculosis infection or evidence on chest-x-ray of clinically significant respiratory disease.
17. PPD skin test within last 12 months
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

McMaster University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fiona M Smaill, MB,ChB

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

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McMaster University Medical Centre

Hamilton, Ontario, Canada

Site Status

Countries

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Canada

References

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Jeyanathan M, Fritz DK, Afkhami S, Aguirre E, Howie KJ, Zganiacz A, Dvorkin-Gheva A, Thompson MR, Silver RF, Cusack RP, Lichty BD, O'Byrne PM, Kolb M, Medina MFC, Dolovich MB, Satia I, Gauvreau GM, Xing Z, Smaill F. Aerosol delivery, but not intramuscular injection, of adenovirus-vectored tuberculosis vaccine induces respiratory-mucosal immunity in humans. JCI Insight. 2022 Feb 8;7(3):e155655. doi: 10.1172/jci.insight.155655.

Reference Type DERIVED
PMID: 34990408 (View on PubMed)

Related Links

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https://www.medrxiv.org/content/10.1101/2021.09.09.21263339v1

Safety and immunopotency of an adenovirus-vectored tuberculosis vaccine delivered via inhaled aerosol to healthy humans: a dose and route comparison phase 1b study

Other Identifiers

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M002

Identifier Type: -

Identifier Source: org_study_id