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

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Phase 1, Open-label Clinical Trial to Evaluate the Safety and Immunogenicity of an Adenovirus-based Tuberculosis Vaccine Administered by Aerosol

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.

Detailed Summary:

This is a phase 1, open label study to evaluate the safety and immunogenicity of a single administration of escalating 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.

36 healthy volunteers will be enrolled and administered escalating doses of vaccine using the AeroNeb Solo Vibrating Mesh Nebulizer. At the highest dose, participants will be randomized to inhaled or intramuscular administration. Cellular immune responses in the lung and peripheral blood will be evaluated


Sponsor: McMaster University

Current Primary Outcome: Number of participants reporting adverse events [ Time Frame: Over 24 weeks ]

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, 16 and 24


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Immunogenicity of escalating doses of Ad5Ag85A administered by aerosol [ Time Frame: Two weeks after vaccination ]
    Change from baseline in the immune responses of specific T-cells in BAL fluid (mucosal) and blood (systemic). Immune responses measured will include interferon Elispot assay, cytokine production and intracellular cytokine staining
  • Immunogenicity of escalating doses of Ad5Ag85A administered by aerosol [ Time Frame: Eight weeks after vaccination ]
  • Immunogenicity of inhaled administration of Ad5Ag85A compared with intramuscular administration [ Time Frame: Two weeks after vaccination ]
  • Immunogenicity of inhaled administration of Ad5Ag85A compared with intramuscular administration [ Time Frame: Eight weeks after vaccination ]
  • Number of participants reporting adverse events with inhaled administration of Ad5Ag85A compared with intramuscular administration [ Time Frame: Over 24 weeks ]
  • Immune responses measured from induced sputum compared with bronchoalveolar lavage [ Time Frame: Two weeks after vaccination ]
  • immune responses measured from induced sputum compared with bronchoalveolar lavage [ Time Frame: Eight weeks after vaccination ]
  • Number of participants developing a positive interferon release assay for TB after vaccination with Ad5Ag85A [ Time Frame: At 16 weeks ]
  • Number of participants reporting adverse events correlated with level of pre-existing anti-adenoviral antibodies [ Time Frame: Over 24 weeks ]
  • Immune response to vaccination correlated with pre-existing anti-adenoviral antibodies [ Time Frame: Two weeks after vaccination ]
  • Immune response to vaccination correlated with pre-existing anti-adenoviral antibodies [ Time Frame: Eight weeks after vaccination ]
  • Number of participants reporting adverse effects correlated with dose of vaccine received by inhalation [ Time Frame: Over 24 weeks ]
  • Immune response to vaccine correlated with dose of vaccine received by inhalation [ Time Frame: Two weeks after vaccination ]
  • Immune response to vaccine correlated with dose of vaccine received by inhalation [ Time Frame: Eight weeks after vaccination ]


Original Secondary Outcome: Same as current

Information By: McMaster University

Dates:
Date Received: December 19, 2014
Date Started: April 2017
Date Completion:
Last Updated: September 23, 2016
Last Verified: September 2016