ClinicalTrials.gov
ClinicalTrials.gov Menu

Aerosol BCG Challenge Trial in Healthy UK Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02709278
Recruitment Status : Active, not recruiting
First Posted : March 16, 2016
Last Update Posted : November 7, 2018
Sponsor:
Collaborator:
University of Birmingham
Information provided by (Responsible Party):
University of Oxford

Brief Summary:
TB041 is a clinical challenge trial primarily to evaluate the safety of BCG challenge administered by the aerosol inhaled route in healthy, BCG naive UK adults. The trial will also look to evaluate and compare the amount of BCG recovered from the lungs and from the skin, following challenge by either the aerosol or the intradermal route.

Condition or disease Intervention/treatment Phase
Tuberculosis Biological: BCG Other: Saline placebo Phase 1

Detailed Description:

Mycobacterium tuberculosis (M.tb) is a pathogen found worldwide that infects humans causing tuberculosis (TB), a transmissible disease resulting in very high mortality and morbidity. It is estimated that a third of the world's population is latently infected with M.tb, and these people carry a 10% lifetime risk of developing active life-threatening disease. In 2013, there were 9 million new cases worldwide and 1.5 million people died of TB. Co-infection with human immunodeficiency virus (HIV) greatly increases risk of TB reactivation and death. TB diagnosis is challenging and drug treatment can be prolonged, harmful, costly and complex. For these reasons an effective vaccine is a global public health priority.

Currently to assess vaccine efficacy against TB there is no reliable alternative to large, randomized controlled trials. These efficacy trials for novel TB vaccines are challenging, time consuming and very costly. For other diseases, such as malaria, challenge studies have been informative. The development of a safe controlled human mycobacterial challenge model which would ultimately be validated against field efficacy studies could greatly facilitate TB vaccine development by being a guide for selecting which candidate TB vaccines to take forwards to large efficacy trials.

TB041 is a clinical challenge trial primarily to evaluate the safety of BCG challenge administered by the aerosol inhaled route in healthy, BCG naive UK adults. The trial will also look to evaluate and compare the amount of BCG recovered from the lungs and from the skin, following challenge by either the aerosol or the intradermal route.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Other
Official Title: A Clinical Challenge Trial to Evaluate Controlled Human Infection With BCG Administered by the Aerosol Inhaled Route Compared With the Intradermal Route in Healthy, BCG-naïve, UK Adult Volunteers
Study Start Date : March 2016
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arm Intervention/treatment
Group 1A: low dose aerosol BCG SSI
3 volunteers receiving BCG SSI at a dose of 1 x 10^3 cfu by the aerosol inhaled route, followed by bronchoscopy.
Biological: BCG
BCG SSI (Groups 1A, 1B, 1C and 1D) & BCG Bulgaria (InterVax) (Groups 2A, 2B, 2C, 2D and 2E)

Group 1B: medium dose aerosol BCG SSI
3 volunteers receiving BCG SSI at a dose of 1 x 10^4 cfu by the aerosol inhaled route, followed by bronchoscopy.
Biological: BCG
BCG SSI (Groups 1A, 1B, 1C and 1D) & BCG Bulgaria (InterVax) (Groups 2A, 2B, 2C, 2D and 2E)

Experimental: Group 1C: standard dose aerosol BCG SSI
12 volunteers receiving BCG SSI at a dose of 1 x 10^5 cfu by the aerosol inhaled route and intradermal saline placebo, followed by bronchoscopy.
Biological: BCG
BCG SSI (Groups 1A, 1B, 1C and 1D) & BCG Bulgaria (InterVax) (Groups 2A, 2B, 2C, 2D and 2E)

Other: Saline placebo
Saline placebo

Experimental: Group 1D: standard dose intradermal BCG SSI
12 volunteers receiving BCG SSI at a dose of 1 x 10^5 cfu by the intradermal route and aerosol inhaled saline placebo, followed by bronchoscopy and punch biopsy at the intradermal injection site.
Biological: BCG
BCG SSI (Groups 1A, 1B, 1C and 1D) & BCG Bulgaria (InterVax) (Groups 2A, 2B, 2C, 2D and 2E)

Other: Saline placebo
Saline placebo

Group 2A: lower than standard dose aerosol BCG Bulgaria
3 volunteers receiving BCG Bulgaria (InterVax) at a dose of 1 x 10^4 cfu by the aerosol inhaled route, followed by bronchoscopy.
Biological: BCG
BCG SSI (Groups 1A, 1B, 1C and 1D) & BCG Bulgaria (InterVax) (Groups 2A, 2B, 2C, 2D and 2E)

Group 2B: close to the standard dose aerosol BCG Bulgaria
3 volunteers receiving BCG Bulgaria (InterVax) at a dose of 1 x 10^5 cfu by the aerosol route, followed by bronchoscopy.
Biological: BCG
BCG SSI (Groups 1A, 1B, 1C and 1D) & BCG Bulgaria (InterVax) (Groups 2A, 2B, 2C, 2D and 2E)

Group 2C: higher than standard dose aerosol BCG Bulgaria
3 volunteers receiving BCG Bulgaria (InterVax) at a dose of 1 x 10^6 cfu by the aerosol inhaled route, followed by bronchoscopy.
Biological: BCG
BCG SSI (Groups 1A, 1B, 1C and 1D) & BCG Bulgaria (InterVax) (Groups 2A, 2B, 2C, 2D and 2E)

Experimental: Group 2D: close to or higher than standard aerosol BCG
9 volunteers receiving BCG Bulgaria (InterVax) at the optimal dose identified from preliminary results obtained from Groups 2B and 2C by the aerosol inhaled route and intradermal saline placebo, followed by bronchoscopy.
Biological: BCG
BCG SSI (Groups 1A, 1B, 1C and 1D) & BCG Bulgaria (InterVax) (Groups 2A, 2B, 2C, 2D and 2E)

Other: Saline placebo
Saline placebo

Experimental: Group 2E: close to or higher than standard intradermal BCG
12 volunteers receiving BCG Bulgaria (InterVax) at the optimal dose identified from preliminary results obtained from Groups 2B and 2C by the intradermal route and aerosol inhaled saline placebo, followed by bronchoscopy and punch biopsy at the intradermal injection site.
Biological: BCG
BCG SSI (Groups 1A, 1B, 1C and 1D) & BCG Bulgaria (InterVax) (Groups 2A, 2B, 2C, 2D and 2E)

Other: Saline placebo
Saline placebo




Primary Outcome Measures :
  1. Adverse Events (AE) [ Time Frame: Up to day 168 ]
    Collection of AE data at each visit and via diary card for 28 days after challenge.


Secondary Outcome Measures :
  1. Quantification of BCG [ Time Frame: At day 14 ]
    Quantification of BCG in bronchoalveolar lavage (BAL) sample and intradermal biopsy sample.


Other Outcome Measures:
  1. Identification of cellular markers of immunity [ Time Frame: Up to day 168 ]
    Established and exploratory markers of innate, cell mediated and humoral immunity in blood and BAL samples will be used to identify cellular markers of immunity to BCG.

  2. Evaluation of aerosol BCG challenge vs intradermal BCG challenge [ Time Frame: Up to day 168 ]
    Laboratory markers of cell mediated and humoral immunity, including ex-vivo ELISpot in blood and intracellular cytokine staining in blood and BAL samples will be used to assess which route of challenge is most effective



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adult aged 18-50 years
  • Resident in or near Oxford (CCVTM or OUH) or Birmingham (NIHR-WTCRF) for the = duration of the trial period
  • Screening IGRA negative
  • Chest radiograph normal
  • No relevant findings in medical history or on physical examination
  • Allow the Investigators to discuss the individual's medical history with their GP
  • Use effective contraception (see below) for the duration of the trial period (females only)
  • Refrain from blood donation during the trial
  • Give written informed consent
  • Allow the Investigator to register volunteer details with a confidential database (The - Over-volunteering Protection Service) to prevent concurrent entry into clinical studies/trials
  • Able and willing (in the Investigator's opinion) to comply with all the trial requirements

Exclusion Criteria:

  • Previously resident for more than 12 months concurrently in a tropical climate where significant non-tuberculous mycobacterial exposure is likely
  • Participation in another research trial involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the trial period
  • Prior vaccination with BCG or any candidate TB vaccine
  • Administration of immunoglobulins and/or any blood products within the three months preceding the planned trial challenge date
  • Clinically significant history of skin disorder, allergy, atopy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse
  • Concurrent oral or systemic steroid medication or the concurrent use of other immunosuppressive agents
  • History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the trial agent, sedative drugs, or any local or general anaesthetic agents
  • Pregnancy, lactation or intention to become pregnant during trial period Any respiratory disease, including asthma
  • Current smoker
  • Clinically significant abnormality on screening chest radiograph
  • Clinically significant abnormality of spirometry
  • Any nasal, pharyngeal, or laryngeal finding which precludes bronchoscopy
  • Current use of any medication taken through the nasal or inhaled route including cocaine or other recreational drugs
  • Clinical, radiological, or laboratory evidence of current active TB disease
  • Past treatment for TB disease
  • Any clinically significant abnormality of screening blood or urine tests
  • Positive HBsAg, HCV or HIV antibodies
  • Any other significant disease, disorder, or finding, which, in the opinion of the Investigator, may either put the volunteer at risk, affect the volunteer's ability to participate in the trial or impair interpretation of the trial data

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): NCT02709278


Locations
United Kingdom
Centre for Clinical Vaccinology and Tropical Medicine , University of Oxford
Oxford, Oxfordshire, United Kingdom, OX3 7LE
Oxford University Hospitals- John Warin Ward, University of Oxford
Oxford, Oxfordshire, United Kingdom, OX3 7LE
NIHR Wellcome Trust Clinical Research Facility, University of Birmingham
Birmingham, West Midlands, United Kingdom, B15 2TH
Sponsors and Collaborators
University of Oxford
University of Birmingham
Investigators
Principal Investigator: Professor Helen McShane University of Oxford
Principal Investigator: Professor Paul Moss University of Birmingham

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT02709278     History of Changes
Other Study ID Numbers: TB041
First Posted: March 16, 2016    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by University of Oxford:
BCG
Aerosol
Tuberculosis
Challenge

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections