TuberculosisPhase 1NCT02709278
Aerosol BCG Challenge Trial in Healthy UK Adults
A Phase 1 study testing BCG in people with Tuberculosis, run by University of Oxford at 3 sites in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- BCG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 7 Mar 2016to 9 May 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
NIHR Wellcome Trust Clinical Research Facility, University of Birmingham
Birmingham, West Midlands, B15 2TH
Centre for Clinical Vaccinology and Tropical Medicine , University of Oxford
Oxford, Oxfordshire, OX3 7LE
Oxford University Hospitals- John Warin Ward, University of Oxford
Oxford, Oxfordshire, OX3 7LE
About this study
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
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.
Read the 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
- Being tested
- BCG, Saline placebo
- Keywords
- BCG, Aerosol, Tuberculosis, Challenge
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCGBiological
BCG SSI (Due to a global shortage of BCG SSI, BCG Bulgaria used in Group 2)
Saline placeboOther
Saline placebo
BCGBiological
BCG Bulgaria (InterVax)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Biological: BCG; Other: 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. Receives: Biological: BCG; Other: 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. Receives: 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. Receives: 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. Receives: 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 Receives: 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 Receives: Other: Saline placebo; Biological: 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 Receives: Other: Saline placebo; Biological: BCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events (AE)
Collection of AE data at each visit and via diary card for 28 days after challenge.
Measured: Up to day 168
Secondary outcomes (1)
Quantification of BCG
Quantification of BCG in bronchoalveolar lavage (BAL) sample and intradermal biopsy sample.
Measured: At day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2016 (estimated)
- Study start7 Mar 2016
- Primary completion9 May 2019
- Study completion9 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- University of Birmingham
- Responsible party
- Sponsor
- Investigators
- Professor Helen McShane, Principal investigator, University of OxfordProfessor Paul Moss, Principal investigator, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02709278
- Sponsor's protocol ID
- TB041
- Status last verified
- Nov 2023
- First submitted
- 12 Feb 2016
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 38621405
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02709278
- Acronym / sponsor ID
- TB041
- Conditions
- Tuberculosis
- Keywords
- BCG, Aerosol, Tuberculosis, Challenge
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- University of Birmingham
- Study start
- 7 Mar 2016 (actual)
- Primary completion
- 9 May 2019 (actual)
- Study completion
- 9 May 2019 (actual)
- First posted
- 16 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Group 1A: low dose aerosol BCG SSI | Other | Biological: BCG3 volunteers receiving BCG SSI at a dose of 1 x 10^3 cfu by the aerosol inhaled route, followed by bronchoscopy. |
| Group 1B: medium dose aerosol BCG SSI | Other | Biological: BCG3 volunteers receiving BCG SSI at a dose of 1 x 10^4 cfu by the aerosol inhaled route, followed by bronchoscopy. |
| Group 1C: standard dose aerosol BCG SSI | Experimental | Biological: BCG, Other: Saline placebo12 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 1D: standard dose intradermal BCG SSI | Experimental | Biological: BCG, Other: Saline placebo12 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 2A: lower than standard dose aerosol BCG Bulgaria | Other | Biological: BCG3 volunteers receiving BCG Bulgaria (InterVax) at a dose of 1 x 10^4 cfu by the aerosol inhaled route, followed by bronchoscopy. |
| Group 2B: close to the standard dose aerosol BCG Bulgaria | Other | Biological: BCG3 volunteers receiving BCG Bulgaria (InterVax) at a dose of 1 x 10^5 cfu by the aerosol route, followed by bronchoscopy. |
| Group 2C: higher than standard dose aerosol BCG Bulgaria | Other | Biological: BCG3 volunteers receiving BCG Bulgaria (InterVax) at a dose of 1 x 10^6 cfu by the aerosol inhaled route, followed by bronchoscopy. |
| Group 2D: close to or higher than standard aerosol BCG | Experimental | Biological: BCG3 volunteers receiving 1 x 10^7 cfu aerosol inhaled BCG Bulgaria (InterVax), followed by bronchoscopy 14 days later |
| Group 2E: close to or higher than standard intradermal BCG | Experimental | Other: Saline placebo, Biological: BCG9 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 2F: 1 log lower than Group 2E | Experimental | Other: Saline placebo, Biological: BCG12 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 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BCGBCG SSI (Due to a global shortage of BCG SSI, BCG Bulgaria used in Group 2) | Biological | 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 |
| Saline placeboSaline placebo | Other | Group 1C: standard dose aerosol BCG SSI, Group 1D: standard dose intradermal BCG SSI, Group 2E: close to or higher than standard intradermal BCG, Group 2F: 1 log lower than Group 2E |
| BCGBCG Bulgaria (InterVax) | Biological | 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, Group 2F: 1 log lower than Group 2E |
Primary outcome
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.
1 secondary outcome
Quantification of BCG
Time frame: At day 14
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Derived from this study: PubMed 38621405Satti 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.
- Individual participant dataSharing planned: Undecided
Related trials for Tuberculosis
RecruitingPhase 4
Short-term Antibiotic Therapy in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
RecruitingObservational study
Paradoxical Tuberculosis Reactions in Patients Without HIV Infection
Tuberculosis
Not yet recruitingPhase 2
Re-evaluating the Duration in Children of TB Treatment
Tuberculosis
RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
Active, not recruitingPhase 3
Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients
Tuberculosis, MDR
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Professor Helen McShane principal investigator
University of Oxford
Professor Paul Moss principal investigator
University of Birmingham
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BCG in people with Tuberculosis, run by University of Oxford at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (AE) (time frame: Up to day 168). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02709278, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.