NCT02709278

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
46

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Mar 2016

Typical duration for phase_1

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 12, 2016

Completed
24 days until next milestone

Study Start

First participant enrolled

March 7, 2016

Completed
9 days until next milestone

First Posted

Study publicly available on registry

March 16, 2016

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 9, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 9, 2019

Completed
Last Updated

November 18, 2023

Status Verified

November 1, 2023

Enrollment Period

3.2 years

First QC Date

February 12, 2016

Last Update Submit

November 14, 2023

Conditions

Tuberculosis

Keywords

BCGAerosolTuberculosisChallenge

Outcome Measures

Primary Outcomes (1)

  • Adverse Events (AE)

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

    Up to day 168

Secondary Outcomes (1)

  • Quantification of BCG

    At day 14

Other Outcomes (2)

  • Identification of cellular markers of immunity

    Up to day 168

  • Evaluation of aerosol BCG challenge vs intradermal BCG challenge

    Up to day 168

Study Arms (10)

Group 1A: low dose aerosol BCG SSI

OTHER

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

Biological: BCG

Group 1B: medium dose aerosol BCG SSI

OTHER

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

Biological: BCG

Group 1C: standard dose aerosol BCG SSI

EXPERIMENTAL

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: BCGOther: Saline placebo

Group 1D: standard dose intradermal BCG SSI

EXPERIMENTAL

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: BCGOther: Saline placebo

Group 2A: lower than standard dose aerosol BCG Bulgaria

OTHER

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

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

OTHER

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

Biological: BCG

Group 2C: higher than standard dose aerosol BCG Bulgaria

OTHER

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

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

EXPERIMENTAL

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

Biological: BCG

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

EXPERIMENTAL

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

Other: Saline placeboBiological: BCG

Group 2F: 1 log lower than Group 2E

EXPERIMENTAL

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

Other: Saline placeboBiological: BCG

Interventions

BCGBIOLOGICAL

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

Group 1A: low dose aerosol BCG SSIGroup 1B: medium dose aerosol BCG SSIGroup 1C: standard dose aerosol BCG SSIGroup 1D: standard dose intradermal BCG SSI
Saline placeboOTHER

Saline placebo

Group 1C: standard dose aerosol BCG SSIGroup 1D: standard dose intradermal BCG SSIGroup 2E: close to or higher than standard intradermal BCGGroup 2F: 1 log lower than Group 2E

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Centre for Clinical Vaccinology and Tropical Medicine , University of Oxford

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Oxford University Hospitals- John Warin Ward, University of Oxford

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

NIHR Wellcome Trust Clinical Research Facility, University of Birmingham

Birmingham, West Midlands, B15 2TH, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 38621405DERIVED

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Study Officials

  • Professor Helen McShane

    University of Oxford

    PRINCIPAL INVESTIGATOR

  • Professor Paul Moss

    University of Birmingham

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 12, 2016

First Posted

March 16, 2016

Study Start

March 7, 2016

Primary Completion

May 9, 2019

Study Completion

May 9, 2019

Last Updated

November 18, 2023

Record last verified: 2023-11

Locations

GB(3)