TuberculosisPhase 1NCT04777721
Aerosol BCG Challenge Study in Historically BCG-vaccinated Volunteers
A Phase 1 study testing BCG Danish in people with Tuberculosis, run by University of Oxford at 1 site in United Kingdom.
Trial summary
The purpose of this study is to evaluate the human clinical response to BCG challenge in historically BCG-vaccinated healthy adult volunteers. It will involve 12 participants in a controlled dose escalation. Bronchoscopies will be performed 14 days post-challenge to measure BCG recovered from bronchial samples. 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 Danish
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 May 2022to 20 Jun 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 adults aged 18-50 years
- Previously vaccinated with the BCG (at least 6 months prior to enrolment, as evidenced by a visible scar or documentation in medical or occupational health records)
- Resident in or near Oxford for the duration of the study period
- Provide written informed consent
- Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner (or review summary care record, if available)
- Allow the investigator to register volunteer details with a confidential database (The Over-volunteering Protection Service) to prevent concurrent entry into clinical studies/trials
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- Agreement to refrain from blood donation during the course of the study
- For women of child-bearing potential only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening, challenge and bronchoscopy
- Able and willing (in the investigator's opinion) to comply with all study requirements
- No clinically relevant findings in medical history or on physical examination
- Screening IGRA negative
- Willing to be tested for evidence of SARS-CoV-2 infection and to allow public health notification of the results
Who cannot join
- Any clinically significant respiratory disease, including asthma
- Current smoker (defined as any smoking including e-cigarettes in the last 3 months)
- History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the study agent, any essential study procedure, sedative drugs, or any local or general anaesthetic agents
- Clinically significant history of skin disorder, allergy, atopy, cancer (except BCC of the skin or CIS of the cervix), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse
- Any autoimmune conditions or immunodeficiency (including HIV)
- Previous diagnosis or treatment for TB disease or latent TB infections
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- Clinical, radiological, or laboratory evidence of current active TB disease or latent TB infection
- Previous receipt of any investigational TB vaccine
- Positive HBsAg, HCV or HIV antibodies
- Concurrent use of oral, inhaled or systemic steroid medication or use for more than 14 days within the last 6 months (steroids used as a cream or ointment are permissible), or the use of other immunosuppressive agents concurrently or for more than 14 days within the last 6 months
- Administration of immunoglobulins and/or any blood products within the three months preceding the planned study challenge date
- Current use of any medication or other drug taken through the nasal or inhaled route including cocaine or other recreational drugs
- Any nasal, pharyngeal, or laryngeal finding which precludes bronchoscopy
- Pregnancy, lactation or intention to become pregnant during study period
- Previously resident for more than 12 months concurrently in a tropical climate where significant non-tuberculous mycobacterial exposure is likely
- Shares a household with someone with clinically significant immunodeficiency (either from infection or medication) who is deemed to be at risk of developing disseminated BCG infection if exposed to BCG
- Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period
- Clinically significant abnormality on screening chest radiograph
- Clinically significant abnormality of lung function testing
- Any clinically significant abnormality of screening blood or urine tests
- Laboratory confirmed (PCR or antibody) SARS-Cov-2 infection, evidence of viral pneumonitis on chest radiograph or a high clinical suspicion of COVID-19 disease in the 3 months preceding enrolment.
- A body mass index (BMI) of <18.5 or >45
- 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 study or impair interpretation of the study data
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Centre for Clinical Vaccinology and Tropical Medicine
Oxford, Oxfordshire, OX37LE
About this study
Official title: A Clinical Challenge Study to Evaluate Controlled Human Infection With BCG Administered by the Aerosol Inhaled Route in Historically BCG-vaccinated Healthy Adult Volunteers
The purpose of this study is to evaluate the human clinical response to BCG challenge in historically BCG-vaccinated healthy adult volunteers. It will involve 12 participants in a controlled dose escalation. Bronchoscopies will be performed 14 days post-challenge to measure BCG recovered from bronchial samples. Blood tests will be taken to look at potential immunological markers of immunity.
Read the detailed description
Tuberculosis (TB) remains one of the deadliest infectious disease killers worldwide. Key research priorities include the development of an effective vaccine.
Currently, the only licensed vaccine against TB is the BCG (Bacille Calmette-Guérin). This works well against TB in childhood but is often ineffective in adults. Developing a new TB vaccine is difficult, as it is hard to determine which will be effective. In other diseases, e.g. influenza or malaria, it is possible to experimentally-infect volunteers with the disease to see if the proposed vaccine is effective. This is called a "controlled human challenge or infection model" and is possible in easily treatable or self-limiting diseases. This is not possible with TB, where treatments may be harmful and complex. Using a related but less infectious bacterium is a feasible alternative.
The BCG is a live attenuated (weakened) strain of the bacteria that causes TB in cattle. The BCG bacteria do not cause disease in healthy individuals. As the BCG and TB bacteria are similar, a challenge model using the BCG as an infectious agent to mimic TB infection is being developed.
Mycobacterium tuberculosis, the bacterium that causes TB, infects people by inhalation into the lungs. Therefore, inhaled BCG more closely imitates TB infection than an injection. A previous (TB041) and current study (TB043) in this group use aerosol inhaled BCG in volunteers who have not received the standard BCG vaccination before.
The purpose of this study is to evaluate the human clinical response to BCG challenge in historically BCG-vaccinated healthy adult volunteers. It will involve 12 participants in a controlled dose escalation. Bronchoscopies will be performed 14 days post-challenge to measure BCG recovered from bronchial samples. Blood tests will be taken to look at potential immunological markers of immunity.
- Conditions
- Tuberculosis
- Being tested
- BCG Danish
- Keywords
- Tuberculosis, BCG, Human challenge, Aerosol BCG challenge
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG DanishBiological
BCG Danish 1331 is on the WHO list of pre-qualified vaccines and has a well-defined side effect profile. BCG is licensed for delivery via the intradermal route. It is not licensed for delivery via the aerosol route.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: 1 x 10^4 cfu aerosol inhaled BCG | Experimental | 3 historically BCG-vaccinated volunteers will receive 1 x 10^4 cfu aerosol inhaled BCG. All Group 1 volunteers will have a bronchoscopy 14 days post challenge. Receives: Biological: BCG Danish |
| Group 2: 1 x 10^5 cfu aerosol inhaled BCG | Experimental | 3 historically BCG-vaccinated volunteers will receive 1 x 10^5 cfu aerosol inhaled BCG. All Group 2 volunteers will have a bronchoscopy 14 days post challenge. Receives: Biological: BCG Danish |
| Group 3: 1 x 10^6 cfu aerosol inhaled BCG | Experimental | 3 historically BCG-vaccinated volunteers will receive 1 x 10^6 cfu aerosol inhaled BCG. All Group 3 volunteers will have a bronchoscopy 14 days post challenge. Receives: Biological: BCG Danish |
| Group 4: 1 x 10^7 cfu aerosol inhaled BCG | Experimental | 3 historically BCG-vaccinated volunteers will receive 1 x 10^7 cfu aerosol inhaled BCG. All Group 3 volunteers will have a bronchoscopy 14 days post challenge. Receives: Biological: BCG Danish |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Quantify BCG Recoverable From Bronchial Sample
Quantification of BCG culture by mycobacterial growth indicator tube (PCR quantification and DNA strip assay speciation as required)
Measured: Day 14
Secondary outcomes (1)
Adverse Events
Evaluation of the human clinical response to BCG challenge via collection of data on adverse events at each visit, via diary cards and lung function test results.
Measured: Up to day 168
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2021
- Study start17 May 2022
- Primary completion20 Jun 2023
- Study completion20 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- This is a phase I dose-escalation clinical challenge study in historically BCG-vaccinated healthy adult volunteers in which BCG will be administered via the aerosol inhaled route. There will be four study groups with three volunteers in each group. Volunteers will be sequentially enrolled into each group in turn based on their availability. The first volunteer in each group will be challenged at least 1 hour apart from any subsequent volunteers. There will be a review of safety data at least 7 days after challenge of all volunteers within each dose group. This safety review will be performed by the Safety Monitoring Committee (SMC). Dose escalation into the next group will only occur if there are no safety concerns. Safety review will include assessment of symptom diary card, safety bloods and lung function results.
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Helen McShane, Professor, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04777721
- Sponsor's protocol ID
- TB044
- Status last verified
- Jan 2025
- First submitted
- 18 Sep 2020
- Last updated
- 6 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Fredsgaard-Jones T, Harris SA, Morrison H, Ateere A, Nassanga B, Ramon RL, Mitton C, Fletcher E, Decker J, Preston-Jones H, Jackson S, Mawer A, Satti I, Barer M, Hinks T, Bettinson H, McShane H. A dose escalation study to evaluate the safety of an aerosol BCG infection in previously BCG-vaccinated healthy human UK adults. Front Immunol. 2024 Nov 14;15:1427371. doi: 10.3389/fimmu.2024.1427371. eCollection 2024.
PubMed 39611145
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Challenge Study to Evaluate Controlled Human Infection With BCG Administered by the Aerosol Inhaled Route in Historically BCG-vaccinated Healthy Adult Volunteers
- ClinicalTrials.gov ID
- NCT04777721
- Acronym / sponsor ID
- TB044
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, BCG, Human challenge, Aerosol BCG challenge
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 17 May 2022 (actual)
- Primary completion
- 20 Jun 2023 (actual)
- Study completion
- 20 Jun 2023 (actual)
- First posted
- 2 Mar 2021 (actual)
- Results
- Posted 6 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the human clinical response to BCG challenge in historically BCG-vaccinated healthy adult volunteers. It will involve 12 participants in a controlled dose escalation. Bronchoscopies will be performed 14 days post-challenge to measure BCG recovered from bronchial samples. Blood tests will be taken to look at potential immunological markers of immunity.
Detailed description
Tuberculosis (TB) remains one of the deadliest infectious disease killers worldwide. Key research priorities include the development of an effective vaccine.
Currently, the only licensed vaccine against TB is the BCG (Bacille Calmette-Guérin). This works well against TB in childhood but is often ineffective in adults. Developing a new TB vaccine is difficult, as it is hard to determine which will be effective. In other diseases, e.g. influenza or malaria, it is possible to experimentally-infect volunteers with the disease to see if the proposed vaccine is effective. This is called a "controlled human challenge or infection model" and is possible in easily treatable or self-limiting diseases. This is not possible with TB, where treatments may be harmful and complex. Using a related but less infectious bacterium is a feasible alternative.
The BCG is a live attenuated (weakened) strain of the bacteria that causes TB in cattle. The BCG bacteria do not cause disease in healthy individuals. As the BCG and TB bacteria are similar, a challenge model using the BCG as an infectious agent to mimic TB infection is being developed.
Mycobacterium tuberculosis, the bacterium that causes TB, infects people by inhalation into the lungs. Therefore, inhaled BCG more closely imitates TB infection than an injection. A previous (TB041) and current study (TB043) in this group use aerosol inhaled BCG in volunteers who have not received the standard BCG vaccination before.
The purpose of this study is to evaluate the human clinical response to BCG challenge in historically BCG-vaccinated healthy adult volunteers. It will involve 12 participants in a controlled dose escalation. Bronchoscopies will be performed 14 days post-challenge to measure BCG recovered from bronchial samples. Blood tests will be taken to look at potential immunological markers of immunity.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- This is a phase I dose-escalation clinical challenge study in historically BCG-vaccinated healthy adult volunteers in which BCG will be administered via the aerosol inhaled route. There will be four study groups with three volunteers in each group. Volunteers will be sequentially enrolled into each group in turn based on their availability. The first volunteer in each group will be challenged at least 1 hour apart from any subsequent volunteers. There will be a review of safety data at least 7 days after challenge of all volunteers within each dose group. This safety review will be performed by the Safety Monitoring Committee (SMC). Dose escalation into the next group will only occur if there are no safety concerns. Safety review will include assessment of symptom diary card, safety bloods and lung function results.
| Arm | Type | Receives |
|---|---|---|
| Group 1: 1 x 10^4 cfu aerosol inhaled BCG | Experimental | Biological: BCG Danish3 historically BCG-vaccinated volunteers will receive 1 x 10^4 cfu aerosol inhaled BCG. All Group 1 volunteers will have a bronchoscopy 14 days post challenge. |
| Group 2: 1 x 10^5 cfu aerosol inhaled BCG | Experimental | Biological: BCG Danish3 historically BCG-vaccinated volunteers will receive 1 x 10^5 cfu aerosol inhaled BCG. All Group 2 volunteers will have a bronchoscopy 14 days post challenge. |
| Group 3: 1 x 10^6 cfu aerosol inhaled BCG | Experimental | Biological: BCG Danish3 historically BCG-vaccinated volunteers will receive 1 x 10^6 cfu aerosol inhaled BCG. All Group 3 volunteers will have a bronchoscopy 14 days post challenge. |
| Group 4: 1 x 10^7 cfu aerosol inhaled BCG | Experimental | Biological: BCG Danish3 historically BCG-vaccinated volunteers will receive 1 x 10^7 cfu aerosol inhaled BCG. All Group 3 volunteers will have a bronchoscopy 14 days post challenge. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Healthy adults aged 18-50 years
- Previously vaccinated with the BCG (at least 6 months prior to enrolment, as evidenced by a visible scar or documentation in medical or occupational health records)
- Resident in or near Oxford for the duration of the study period
- Provide written informed consent
- Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner (or review summary care record, if available)
Key exclusion criteria (23 listed)
- Any clinically significant respiratory disease, including asthma
- Current smoker (defined as any smoking including e-cigarettes in the last 3 months)
- History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the study agent, any essential study procedure, sedative drugs, or any local or general anaesthetic agents
- Clinically significant history of skin disorder, allergy, atopy, cancer (except BCC of the skin or CIS of the cervix), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse
- Any autoimmune conditions or immunodeficiency (including HIV)
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 |
|---|---|---|
| BCG DanishBCG Danish 1331 is on the WHO list of pre-qualified vaccines and has a well-defined side effect profile. BCG is licensed for delivery via the intradermal route. It is not licensed for delivery via the aerosol route. | Biological | Group 1: 1 x 10^4 cfu aerosol inhaled BCG, Group 2: 1 x 10^5 cfu aerosol inhaled BCG, Group 3: 1 x 10^6 cfu aerosol inhaled BCG, Group 4: 1 x 10^7 cfu aerosol inhaled BCG |
Primary outcome
To Quantify BCG Recoverable From Bronchial Sample
Time frame: Day 14
Quantification of BCG culture by mycobacterial growth indicator tube (PCR quantification and DNA strip assay speciation as required)
1 secondary outcome
Adverse Events
Time frame: Up to day 168
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39611145Fredsgaard-Jones T, Harris SA, Morrison H, Ateere A, Nassanga B, Ramon RL, Mitton C, Fletcher E, Decker J, Preston-Jones H, Jackson S, Mawer A, Satti I, Barer M, Hinks T, Bettinson H, McShane H. A dose escalation study to evaluate the safety of an aerosol BCG infection in previously BCG-vaccinated healthy human UK adults. Front Immunol. 2024 Nov 14;15:1427371. doi: 10.3389/fimmu.2024.1427371. eCollection 2024.
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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.
Helen McShane, Professor principal investigator
University of Oxford
1 site 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 Danish in people with Tuberculosis, run by University of Oxford at 1 site 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 12 inclusion and 23 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 6 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Yes. Results are posted in the registry (first posted 6 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
To Quantify BCG Recoverable From Bronchial Sample (time frame: Day 14). 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 NCT04777721, 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 6 Feb 2025.