Aerosol BCG Challenge Trial in Healthy UK Adults

NCT ID: NCT02709278

Last Updated: 2023-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-07
• Study Completion Date: 2019-05-09

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.

Conditions

Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: OTHER

BCG

Intervention Type: BIOLOGICAL

BCG SSI (Due to a global shortage of BCG SSI, BCG Bulgaria used in Group 2)

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.

Group Type: OTHER

BCG

Intervention Type: BIOLOGICAL

BCG SSI (Due to a global shortage of BCG SSI, BCG Bulgaria used in Group 2)

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.

Group Type: EXPERIMENTAL

BCG

Intervention Type: BIOLOGICAL

BCG SSI (Due to a global shortage of BCG SSI, BCG Bulgaria used in Group 2)

Saline placebo

Intervention Type: OTHER

Saline placebo

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.

Group Type: EXPERIMENTAL

BCG

Intervention Type: BIOLOGICAL

BCG SSI (Due to a global shortage of BCG SSI, BCG Bulgaria used in Group 2)

Saline placebo

Intervention Type: OTHER

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.

Group Type: OTHER

BCG

Intervention Type: BIOLOGICAL

BCG Bulgaria (InterVax)

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.

Group Type: OTHER

BCG

Intervention Type: BIOLOGICAL

BCG Bulgaria (InterVax)

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.

Group Type: OTHER

BCG

Intervention Type: BIOLOGICAL

BCG Bulgaria (InterVax)

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

3 volunteers receiving 1 x 10\^7 cfu aerosol inhaled BCG Bulgaria (InterVax), followed by bronchoscopy 14 days later

Group Type: EXPERIMENTAL

BCG

Intervention Type: BIOLOGICAL

BCG Bulgaria (InterVax)

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

9 volunteers receiving the optimal dose of aerosol inhaled BCG Bulgaria (InterVax) identified from preliminary results obtained from Groups 2C and 2D, and ID saline placebo, followed by bronchoscopy 14 days later

Group Type: EXPERIMENTAL

Saline placebo

Intervention Type: OTHER

Saline placebo

BCG

Intervention Type: BIOLOGICAL

BCG Bulgaria (InterVax)

Group 2F: 1 log lower than Group 2E

12 volunteers will receive aerosol inhaled saline placebo and intradermal BCG Bulgaria (InterVax), at a dose a log lower than 2E then bronchoscopy and punch biopsy

Group Type: EXPERIMENTAL

Saline placebo

Intervention Type: OTHER

Saline placebo

BCG

Intervention Type: BIOLOGICAL

BCG Bulgaria (InterVax)

Interventions

BCG

BCG SSI (Due to a global shortage of BCG SSI, BCG Bulgaria used in Group 2)

Intervention Type: BIOLOGICAL

Saline placebo

Saline placebo

Intervention Type: OTHER

BCG

BCG Bulgaria (InterVax)

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Birmingham

OTHER

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Professor Helen McShane

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Professor Paul Moss

Role: PRINCIPAL_INVESTIGATOR

University of Birmingham

Locations

Centre for Clinical Vaccinology and Tropical Medicine , University of Oxford

Oxford, Oxfordshire, United Kingdom

Oxford University Hospitals- John Warin Ward, University of Oxford

Oxford, Oxfordshire, United Kingdom

NIHR Wellcome Trust Clinical Research Facility, University of Birmingham

Birmingham, West Midlands, United Kingdom

Countries

United Kingdom

References

Satti I, Marshall JL, Harris SA, Wittenberg R, Tanner R, Lopez Ramon R, Wilkie M, Ramos Lopez F, Riste M, Wright D, Peralta Alvarez MP, Williams N, Morrison H, Stylianou E, Folegatti P, Jenkin D, Vermaak S, Rask L, Cabrera Puig I, Powell Doherty R, Lawrie A, Moss P, Hinks T, Bettinson H, McShane H. Safety of a controlled human infection model of tuberculosis with aerosolised, live-attenuated Mycobacterium bovis BCG versus intradermal BCG in BCG-naive adults in the UK: a dose-escalation, randomised, controlled, phase 1 trial. Lancet Infect Dis. 2024 Aug;24(8):909-921. doi: 10.1016/S1473-3099(24)00143-9. Epub 2024 Apr 12.

Reference Type: DERIVED

PMID: 38621405 (View on PubMed)

Other Identifiers

TB041

Identifier Type: -

Identifier Source: org_study_id