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Trial record 29 of 139 for:    vaccine | Tuberculosis

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

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ClinicalTrials.gov Identifier: NCT02337270
Recruitment Status : Recruiting
First Posted : January 13, 2015
Last Update Posted : September 11, 2017
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
McMaster University

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 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


Study Type : Interventional  (Clinical Trial)
Estimated 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 : September 5, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : April 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

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 10^7 Ad5Ag85A by aerosol at day 0
Biological: Ad5Ag85A
Aerosol administration of Ad5Ag85A

Experimental: Group 3 Aerosol
Receive 10^8 Ad5Ag85A be 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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. Immunogenicity of escalating doses of Ad5Ag85A administered by aerosol [ Time Frame: Eight weeks after vaccination ]
  3. Immunogenicity of inhaled administration of Ad5Ag85A compared with intramuscular administration [ Time Frame: Two weeks after vaccination ]
  4. Immunogenicity of inhaled administration of Ad5Ag85A compared with intramuscular administration [ Time Frame: Eight weeks after vaccination ]
  5. Number of participants reporting adverse events with inhaled administration of Ad5Ag85A compared with intramuscular administration [ Time Frame: Over 24 weeks ]
  6. Immune responses measured from induced sputum compared with bronchoalveolar lavage [ Time Frame: Two weeks after vaccination ]
  7. immune responses measured from induced sputum compared with bronchoalveolar lavage [ Time Frame: Eight weeks after vaccination ]
  8. Number of participants developing a positive interferon release assay for TB after vaccination with Ad5Ag85A [ Time Frame: At 16 weeks ]
  9. Number of participants reporting adverse events correlated with level of pre-existing anti-adenoviral antibodies [ Time Frame: Over 24 weeks ]
  10. Immune response to vaccination correlated with pre-existing anti-adenoviral antibodies [ Time Frame: Two weeks after vaccination ]
  11. Immune response to vaccination correlated with pre-existing anti-adenoviral antibodies [ Time Frame: Eight weeks after vaccination ]
  12. Number of participants reporting adverse effects correlated with dose of vaccine received by inhalation [ Time Frame: Over 24 weeks ]
  13. Immune response to vaccine correlated with dose of vaccine received by inhalation [ Time Frame: Two weeks after vaccination ]
  14. Immune response to vaccine correlated with dose of vaccine received by inhalation [ Time Frame: Eight weeks after vaccination ]


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 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.
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02337270


Contacts
Contact: Fiona M Smaill, MB,ChB 1-905-521-2100 ext 74190 smaill@mcmaster.ca
Contact: Zhou Xing, MD, PhD 1-905-525-9140 ext 22354 xingz@mcmaster.ca

Locations
Canada, Ontario
McMaster University Medical Centre Recruiting
Hamilton, Ontario, Canada, L8N 3Z5
Contact: Fiona M Smaill, MD    905-521-2100 ext 76332    smaill@mcmaster.ca   
Contact: Zhou Xing, PhD    905-525-9140 ext 22354    xingz@mcmaster.ca   
Principal Investigator: Fiona M Smaill, MD         
Sponsors and Collaborators
McMaster University
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Fiona M Smaill, MB,ChB McMaster University

Responsible Party: McMaster University
ClinicalTrials.gov Identifier: NCT02337270     History of Changes
Other Study ID Numbers: M002
First Posted: January 13, 2015    Key Record Dates
Last Update Posted: September 11, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by McMaster University:
Tuberculosis
Vaccine
Aerosol
Adenovirus
Immunogenicity

Additional relevant MeSH terms:
Tuberculosis
Vaccines
Adenoviridae Infections
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
DNA Virus Infections
Virus Diseases
Immunologic Factors
Physiological Effects of Drugs