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

NCT02337270 | Completed Phase 1 DMC

• 1 other identifier: M002
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tuberculosis

Keywords

Tuberculosis; Vaccine; Aerosol; Adenovirus; Immunogenicity

Outcome Measures

Primary Outcomes (1)

• Number of participants reporting adverse events

  Adverse events will be assessed according to the CTCAE Expanded Common Toxicity Criteria at 48-72 hours after vaccination, and at weeks 2, 4, 8, 12, 16 and 24

  Over 24 weeks

Secondary Outcomes (14)

• Immunogenicity of one of two doses of Ad5Ag85A administered by aerosol

  Two weeks after vaccination

• Immunogenicity of one of two doses of Ad5Ag85A administered by aerosol

  Eight (first cohort) or twelve (second cohort) weeks after vaccination

• Immunogenicity of inhaled administration of Ad5Ag85A compared with intramuscular administration

  Two weeks after vaccination

• Immunogenicity of inhaled administration of Ad5Ag85A compared with intramuscular administration

  Twelve weeks after vaccination

• Number of participants reporting adverse events with inhaled administration of Ad5Ag85A compared with intramuscular administration

  Over 24 weeks

Study Arms (3)

Group 1 Aerosol

EXPERIMENTAL

Receive 10\^6 Ad5Ag85A by aerosol at day 0

Biological: Ad5Ag85A

Group 2 Aerosol

EXPERIMENTAL

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

Biological: Ad5Ag85A

Group 3 Intramuscular

EXPERIMENTAL

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

Biological: Ad5Ag85A

Interventions

Ad5Ag85A BIOLOGICAL

Aerosol administration of Ad5Ag85A

Group 1 Aerosol; Group 2 Aerosol; Group 3 Intramuscular

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy human subjects who are between 18 and 55 years of age with a history of BCG vaccination.
• HIV antibody negative
• Able to understand and comply with protocol requirements and instructions; able to attend scheduled study visits and complete required investigations.
• 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)
• For men, using barrier contraception for the duration of the study

You may not qualify if:

• Pregnant or lactating women
• 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.
• 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
• Subjects with a history of respiratory disease, e.g. asthma, chronic bronchitis, chronic obstructive pulmonary disease (COPD).
• Current smokers, including e-cigarettes, and ex-smokers who have quit within the last year, as reported by the subject
• Subjects with clinically significant abnormality of baseline spirometry tests
• Any health-related condition for which study bronchoscopy is contraindicated
• 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 \[consistent with latent TB infection\].
• 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.
• Subjects whose use of alcohol or drugs would, in the opinion of the investigator, interfere with adherence to the study protocol.
• 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.
• Failure to provide written consent.
• Known allergy to vaccine components
• Previous vaccination with Ad5Ag85A or any other experimental TB vaccine
• 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)

Sponsors & Collaborators

• McMaster University: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

Related Publications (1)

• 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.

  PMID: 34990408 DERIVED

Related Links

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

MeSH Terms

Conditions

Tuberculosis; Adenoviridae Infections

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; DNA Virus Infections; Virus Diseases

Study Officials

• Fiona M Smaill, MB,ChB

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2014
• First Posted: January 13, 2015
• Study Start: September 5, 2017
• Primary Completion: September 7, 2021
• Study Completion: September 7, 2021
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

CA (1)