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Aerosol BCG Challenge Trial in Healthy UK Adults

Primary Purpose

Tuberculosis

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
BCG
Saline placebo
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Tuberculosis focused on measuring BCG, Aerosol, Tuberculosis, Challenge

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Centre for Clinical Vaccinology and Tropical Medicine , University of Oxford
  • Oxford University Hospitals- John Warin Ward, University of Oxford
  • NIHR Wellcome Trust Clinical Research Facility, University of Birmingham

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Other

Other

Experimental

Experimental

Other

Other

Other

Experimental

Experimental

Arm Label

Group 1A: low dose aerosol BCG SSI

Group 1B: medium dose aerosol BCG SSI

Group 1C: standard dose aerosol BCG SSI

Group 1D: standard dose intradermal BCG SSI

Group 2A: lower than standard dose aerosol BCG Bulgaria

Group 2B: close to the standard dose aerosol BCG Bulgaria

Group 2C: higher than standard dose aerosol BCG Bulgaria

Group 2D: close to or higher than standard aerosol BCG

Group 2E: close to or higher than standard intradermal BCG

Arm Description

3 volunteers receiving BCG SSI at a dose of 1 x 10^3 cfu by the aerosol inhaled route, followed by bronchoscopy.

3 volunteers receiving BCG SSI at a dose of 1 x 10^4 cfu by the aerosol inhaled route, followed by bronchoscopy.

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.

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.

3 volunteers receiving BCG Bulgaria (InterVax) at a dose of 1 x 10^4 cfu by the aerosol inhaled route, followed by bronchoscopy.

3 volunteers receiving BCG Bulgaria (InterVax) at a dose of 1 x 10^5 cfu by the aerosol route, followed by bronchoscopy.

3 volunteers receiving BCG Bulgaria (InterVax) at a dose of 1 x 10^6 cfu by the aerosol inhaled route, followed by bronchoscopy.

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.

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.

Outcomes

Primary Outcome Measures

Adverse Events (AE)
Collection of AE data at each visit and via diary card for 28 days after challenge.

Secondary Outcome Measures

Quantification of BCG
Quantification of BCG in bronchoalveolar lavage (BAL) sample and intradermal biopsy sample.

Full Information

First Posted
February 12, 2016
Last Updated
October 29, 2019
Sponsor
University of Oxford
Collaborators
University of Birmingham
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1. Study Identification

Unique Protocol Identification Number
NCT02709278
Brief Title
Aerosol BCG Challenge Trial in Healthy UK Adults
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 Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
March 7, 2016 (Actual)
Primary Completion Date
May 9, 2019 (Actual)
Study Completion Date
May 9, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford
Collaborators
University of Birmingham

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
BCG, Aerosol, Tuberculosis, Challenge

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
46 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1A: low dose aerosol BCG SSI
Arm Type
Other
Arm Description
3 volunteers receiving BCG SSI at a dose of 1 x 10^3 cfu by the aerosol inhaled route, followed by bronchoscopy.
Arm Title
Group 1B: medium dose aerosol BCG SSI
Arm Type
Other
Arm Description
3 volunteers receiving BCG SSI at a dose of 1 x 10^4 cfu by the aerosol inhaled route, followed by bronchoscopy.
Arm Title
Group 1C: standard dose aerosol BCG SSI
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 1D: standard dose intradermal BCG SSI
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 2A: lower than standard dose aerosol BCG Bulgaria
Arm Type
Other
Arm Description
3 volunteers receiving BCG Bulgaria (InterVax) at a dose of 1 x 10^4 cfu by the aerosol inhaled route, followed by bronchoscopy.
Arm Title
Group 2B: close to the standard dose aerosol BCG Bulgaria
Arm Type
Other
Arm Description
3 volunteers receiving BCG Bulgaria (InterVax) at a dose of 1 x 10^5 cfu by the aerosol route, followed by bronchoscopy.
Arm Title
Group 2C: higher than standard dose aerosol BCG Bulgaria
Arm Type
Other
Arm Description
3 volunteers receiving BCG Bulgaria (InterVax) at a dose of 1 x 10^6 cfu by the aerosol inhaled route, followed by bronchoscopy.
Arm Title
Group 2D: close to or higher than standard aerosol BCG
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 2E: close to or higher than standard intradermal BCG
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
BCG
Intervention Description
BCG SSI (Groups 1A, 1B, 1C and 1D) & BCG Bulgaria (InterVax) (Groups 2A, 2B, 2C, 2D and 2E)
Intervention Type
Other
Intervention Name(s)
Saline placebo
Intervention Description
Saline placebo
Primary Outcome Measure Information:
Title
Adverse Events (AE)
Description
Collection of AE data at each visit and via diary card for 28 days after challenge.
Time Frame
Up to day 168
Secondary Outcome Measure Information:
Title
Quantification of BCG
Description
Quantification of BCG in bronchoalveolar lavage (BAL) sample and intradermal biopsy sample.
Time Frame
At day 14
Other Pre-specified Outcome Measures:
Title
Identification of cellular markers of immunity
Description
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.
Time Frame
Up to day 168
Title
Evaluation of aerosol BCG challenge vs intradermal BCG challenge
Description
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
Time Frame
Up to day 168

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Professor Helen McShane
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Professor Paul Moss
Organizational Affiliation
University of Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Clinical Vaccinology and Tropical Medicine , University of Oxford
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7LE
Country
United Kingdom
Facility Name
Oxford University Hospitals- John Warin Ward, University of Oxford
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7LE
Country
United Kingdom
Facility Name
NIHR Wellcome Trust Clinical Research Facility, University of Birmingham
City
Birmingham
State/Province
West Midlands
ZIP/Postal Code
B15 2TH
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Aerosol BCG Challenge Trial in Healthy UK Adults

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