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

Sponsor

McMaster University (Other)

Overall Status

Completed

CT.gov ID

NCT02337270

Collaborator

Canadian Institutes of Health Research (CIHR) (Other)

Enrollment

Location

Arms

48.1

Actual Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis	Biological: Ad5Ag85A	Phase 1

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Sep 5, 2017

Actual Primary Completion Date :

Sep 7, 2021

Actual Study Completion Date :

Sep 7, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Aerosol Receive 10^6 Ad5Ag85A by aerosol at day 0	Biological: Ad5Ag85A Aerosol administration of Ad5Ag85A
Experimental: Group 2 Aerosol Receive 2x10^6 Ad5Ag85A by aerosol at day 0	Biological: Ad5Ag85A Aerosol administration of Ad5Ag85A
Experimental: Group 3 Intramuscular Receive 10^8 Ad5Ag85A by intramuscular injection at day 0	Biological: Ad5Ag85A Aerosol administration of Ad5Ag85A

Arm

Intervention/Treatment

Experimental: Group 1 Aerosol

Receive 10^6 Ad5Ag85A by aerosol at day 0

Biological: Ad5Ag85A

Aerosol administration of Ad5Ag85A

Experimental: Group 2 Aerosol

Receive 2x10^6 Ad5Ag85A by aerosol at day 0

Biological: Ad5Ag85A

Aerosol administration of Ad5Ag85A

Experimental: Group 3 Intramuscular

Receive 10^8 Ad5Ag85A by intramuscular injection at day 0

Biological: Ad5Ag85A

Aerosol administration of Ad5Ag85A

Outcome Measures

Primary Outcome Measures

Number of participants reporting adverse events [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, 12, 16 and 24

Secondary Outcome Measures

Immunogenicity of one of two doses of Ad5Ag85A administered by aerosol [Two weeks after vaccination]
Change from baseline in the immune responses of specific T-cells in bronchoalveolar lavage [BAL] fluid (mucosal) and blood (systemic). Immune responses measured will include interferon Elispot assay, cytokine production and intracellular cytokine staining
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]
Immune responses measured from induced sputum compared with bronchoalveolar lavage [Two weeks after vaccination]
For first cohort of 8 participants only
immune responses measured from induced sputum compared with bronchoalveolar lavage [Eight weeks after vaccination]
For first cohort of 8 participants only
Number of participants developing a positive interferon release assay for TB after vaccination with Ad5Ag85A [At 16 weeks]
For first cohort of 8 patients only
Number of participants reporting adverse events correlated with level of pre-existing anti-adenoviral antibodies [Over 24 weeks]
Immune response to vaccination correlated with pre-existing anti-adenoviral antibodies [Two weeks after vaccination]
Immune response to vaccination correlated with pre-existing anti-adenoviral antibodies [Eight weeks after vaccination]
Number of participants reporting adverse effects correlated with dose of vaccine received by inhalation [Over 24 weeks]
Immune response to vaccine correlated with dose of vaccine received by inhalation [Two weeks after vaccination]
Immune response to vaccine correlated with dose of vaccine received by inhalation [Eight or 12 weeks after vaccination]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

Exclusion Criteria:

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)
Any abnormality on chest x-ray suggestive of active or remote tuberculosis infection or evidence on chest-x-ray of clinically significant respiratory disease.
PPD skin test within last 12 months