TuberculosisNCT02088892
A Clinical Challenge Study of BCG in Healthy Volunteers
A study testing BCG SSI and BCG Tice in people with Tuberculosis, run by University of Oxford at 2 sites in United Kingdom.
Trial summary
TB031 is a challenge study comparing two different strains of the Bacille Calmette-Guérin (BCG) vaccine at standard and high dose. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- BCG SSI and BCG Tice
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Mar 2014to Jan 2015
- Phase
- Interventional
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Volunteers must meet all of the following criteria to enter the study:
- Healthy adult aged 18-55 years
- BCG naïve
- Resident in or near Oxford (for CCTVM) or Birmingham (for WTCRF) for the duration of the study period
- No relevant findings in medical history or on physical examination
- Allow the Investigators to discuss the volunteer's medical history with their GP
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- Use effective contraception for the duration of the study period (females only)
- Agreement to refrain from blood donation during the duration of the study
- Give written informed consent
- Allow the Investigator to register volunteer details with a confidential database to prevent concurrent entry into clinical trials
- Able and willing (in the Investigator's opinion) to comply with all the study requirements
Who cannot join
- Volunteers must meet none of the following criteria to enter the study:
- Laboratory evidence at screening of latent M. tb infection as indicated by a positive ELISPOT response to ESAT6 or CFP10 antigens
- Clinical, radiological, or laboratory evidence of current active TB disease
- Previous vaccination with BCG, or any candidate TB vaccine
- Within the last year had close household contact with an individual with smear positive pulmonary tuberculosis
- Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse
Show all 16Show fewer
- History of serious psychiatric condition
- 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 challenge agent
- Any abnormality of screening blood or urine tests that is deemed to be clinically significant or that may compromise the safety of the volunteer in the study
- Positive HBsAg, HCV or HIV antibodies
- Female confirmed pregnant or intention to become pregnant during study period, or currently lactating
- Current involvement in another trial that involves regular blood tests or an investigational medicinal product
- Use of an investigational medicinal product or non-registered drug, live vaccine, or investigational medical device for four weeks prior to dosing with the study challenge agent
- Administration of immunoglobulins and/or any blood products within the three months preceding the planned challenge date
- Any other significant disease, disorder, or finding, which, in the opinion of the Investigator, may either put the volunteer at risk, or may influence the result of the study, or may affect the volunteer's ability to participate in the study
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
The Wellcome Trust Clinical Research Facility, University of Birmingham
Birmingham, West Midlands, B15 2TB
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford
Oxford, Oxfordshire, OX3 7LE
About this study
Official title: A Clinical Challenge Study to Quantify BCG at the Challenge Site of Healthy Volunteers Receiving Either Intradermal BCG SSI or BCG TICE at Standard or High Dose
TB031 is a challenge study comparing two different strains of the Bacille Calmette-Guérin (BCG) vaccine at standard and high dose.
Read the detailed description
Currently, to assess vaccine efficacy against tuberculosis (TB) there is no alternative to large randomized controlled trials. These efficacy trials for novel TB vaccines are difficult, long and very costly. For this reason there is an urgent need for a valid, reliable, and strong correlate of protection which can help distinguish between candidate TB vaccines undergoing phase I trials, and thereby allow the vaccine development field to advance more quickly, and in a more cost-effective manner.
This study aims to address the current lack of immunological correlates in the TB vaccine field. As an alternative to phase II field trials, human challenge models can provide an evaluation of preliminary efficacy of vaccine candidates. Challenge models, with their concept of deliberate infectious challenge of human volunteers, have been well established for pathogens such as malaria, typhoid and dengue, and these models have greatly facilitated vaccine development. At present there is no safe human challenge model of Mycobacterium tuberculosis (M. tb) infection to enable proof-of-concept efficacy evaluation of candidate vaccines.
Whilst scientists cannot use M. tb as a challenge agent to evaluate efficacy in a clinical trial for safety and ethical reasons, they can use another mycobacterium, attenuated Mycobacterium bovis, as a surrogate for M. tb infection. Attenuated Mycobacterium bovis is the mycobacterial strain in BCG and is safe to use in humans. An effective vaccine against M. tb should also be effective against BCG. After injection into humans, BCG replicates, and an effective TB vaccine should reduce this BCG replication. The BCG challenge model is based on this premise. In the human BCG challenge model, BCG is administered intradermally and the degree of BCG growth suppression is quantified by analysing the tissue obtained in a punch biopsy of volunteers' skin over the BCG 'challenge' site.
This study aims to use two different strains of BCG, each at standard and high dose, to optimise this BCG challenge model.
- Conditions
- Tuberculosis
- Being tested
- BCG SSI, BCG Tice
- Keywords
- BCG challenge study
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG SSIDrug
Also called Bacille Calmette-Guérin Statens Serum Institute (BCG SSI)
Intradermal injection
BCG TiceDrug
Also called Bacille Calmette-Guérin Tice
Intradermal injection
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | 10 BCG-naïve subjects receiving intradermal BCG SSI at standard dose (2-8 x 10^5 cfu) followed by a punch biopsy at the challenge site 14 days later. Receives: Drug: BCG SSI |
| Group B | Experimental | 10 BCG-naïve subjects receiving BCG Tice at standard dose (2-8 x 10^5 cfu) followed by a punch biopsy at the challenge site 14 days later. Receives: Drug: BCG Tice |
| Group C | Experimental | 10 BCG-naïve subjects receiving intradermal BCG SSI at high dose (6-24 x 10^5 cfu) followed by a punch biopsy at the challenge site 14 days later. Receives: Drug: BCG SSI |
| Group D | Experimental | 10 BCG-naïve subjects receiving intradermal BCG Tice at high dose (6-24 x 10^5 cfu) followed by a punch biopsy at the challenge site 14 days later. Receives: Drug: BCG Tice |
| Group E | Experimental | 8-12 BCG-naïve subjects receiving the optimal strain and dose of intradermal BCG identified from preliminary results obtained from Group A, B, C and D, followed by a punch biopsy at the challenge site 14 days later. Receives: Drug: BCG SSI; Drug: BCG Tice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantity of BCG at challenge site
To evaluate and compare the amount of BCG (measured by CFU count and PCR) from a biopsy taken from the intradermal BCG challenge site in healthy BCG-naïve adults receiving either BCG SSI or BCG Tice at either standard or high dose
Measured: At Day 14
Secondary outcomes (1)
Immune response markers
To identify laboratory markers of the immune response that correlate with the levels of mycobacterial suppression at the BCG challenge site
Measured: Up to Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2014 (estimated)
- Study startMar 2014
- Primary completionJan 2015
- Study completionJan 2015
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 N/A
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Aeras, University of Birmingham
- Responsible party
- Sponsor
- Investigators
- Helen McShane, Study director, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02088892
- Sponsor's protocol ID
- TB031
- Status last verified
- Jan 2015
- First submitted
- 10 Mar 2014
- Last updated
- 22 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Minhinnick A, Harris S, Wilkie M, Peter J, Stockdale L, Manjaly-Thomas ZR, Vermaak S, Satti I, Moss P, McShane H. Optimization of a Human Bacille Calmette-Guerin Challenge Model: A Tool to Evaluate Antimycobacterial Immunity. J Infect Dis. 2016 Mar 1;213(5):824-30. doi: 10.1093/infdis/jiv482. Epub 2015 Oct 8.
PubMed 26450421
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Challenge Study to Quantify BCG at the Challenge Site of Healthy Volunteers Receiving Either Intradermal BCG SSI or BCG TICE at Standard or High Dose
- ClinicalTrials.gov ID
- NCT02088892
- Acronym / sponsor ID
- TB031
- Conditions
- Tuberculosis
- Keywords
- BCG challenge study
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Aeras, University of Birmingham
- Study start
- Mar 2014
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 17 Mar 2014 (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.
TB031 is a challenge study comparing two different strains of the Bacille Calmette-Guérin (BCG) vaccine at standard and high dose.
Detailed description
Currently, to assess vaccine efficacy against tuberculosis (TB) there is no alternative to large randomized controlled trials. These efficacy trials for novel TB vaccines are difficult, long and very costly. For this reason there is an urgent need for a valid, reliable, and strong correlate of protection which can help distinguish between candidate TB vaccines undergoing phase I trials, and thereby allow the vaccine development field to advance more quickly, and in a more cost-effective manner.
This study aims to address the current lack of immunological correlates in the TB vaccine field. As an alternative to phase II field trials, human challenge models can provide an evaluation of preliminary efficacy of vaccine candidates. Challenge models, with their concept of deliberate infectious challenge of human volunteers, have been well established for pathogens such as malaria, typhoid and dengue, and these models have greatly facilitated vaccine development. At present there is no safe human challenge model of Mycobacterium tuberculosis (M. tb) infection to enable proof-of-concept efficacy evaluation of candidate vaccines.
Whilst scientists cannot use M. tb as a challenge agent to evaluate efficacy in a clinical trial for safety and ethical reasons, they can use another mycobacterium, attenuated Mycobacterium bovis, as a surrogate for M. tb infection. Attenuated Mycobacterium bovis is the mycobacterial strain in BCG and is safe to use in humans. An effective vaccine against M. tb should also be effective against BCG. After injection into humans, BCG replicates, and an effective TB vaccine should reduce this BCG replication. The BCG challenge model is based on this premise. In the human BCG challenge model, BCG is administered intradermally and the degree of BCG growth suppression is quantified by analysing the tissue obtained in a punch biopsy of volunteers' skin over the BCG 'challenge' site.
This study aims to use two different strains of BCG, each at standard and high dose, to optimise this BCG challenge model.
Study design
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: BCG SSI10 BCG-naïve subjects receiving intradermal BCG SSI at standard dose (2-8 x 10^5 cfu) followed by a punch biopsy at the challenge site 14 days later. |
| Group B | Experimental | Drug: BCG Tice10 BCG-naïve subjects receiving BCG Tice at standard dose (2-8 x 10^5 cfu) followed by a punch biopsy at the challenge site 14 days later. |
| Group C | Experimental | Drug: BCG SSI10 BCG-naïve subjects receiving intradermal BCG SSI at high dose (6-24 x 10^5 cfu) followed by a punch biopsy at the challenge site 14 days later. |
| Group D | Experimental | Drug: BCG Tice10 BCG-naïve subjects receiving intradermal BCG Tice at high dose (6-24 x 10^5 cfu) followed by a punch biopsy at the challenge site 14 days later. |
| Group E | Experimental | Drug: BCG SSI, Drug: BCG Tice8-12 BCG-naïve subjects receiving the optimal strain and dose of intradermal BCG identified from preliminary results obtained from Group A, B, C and D, followed by a punch biopsy at the challenge site 14 days later. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Healthy adult aged 18-55 years
- BCG naïve
- Resident in or near Oxford (for CCTVM) or Birmingham (for WTCRF) for the duration of the study period
- No relevant findings in medical history or on physical examination
- Allow the Investigators to discuss the volunteer's medical history with their GP
Key exclusion criteria (16 listed)
- Laboratory evidence at screening of latent M. tb infection as indicated by a positive ELISPOT response to ESAT6 or CFP10 antigens
- Clinical, radiological, or laboratory evidence of current active TB disease
- Previous vaccination with BCG, or any candidate TB vaccine
- Within the last year had close household contact with an individual with smear positive pulmonary tuberculosis
- Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, respiratory 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 |
|---|---|---|
| BCG SSIAlso: Bacille Calmette-Guérin Statens Serum Institute (BCG SSI)Intradermal injection | Drug | Group A, Group C, Group E |
| BCG TiceAlso: Bacille Calmette-Guérin TiceIntradermal injection | Drug | Group B, Group D, Group E |
Primary outcome
Quantity of BCG at challenge site
Time frame: At Day 14
To evaluate and compare the amount of BCG (measured by CFU count and PCR) from a biopsy taken from the intradermal BCG challenge site in healthy BCG-naïve adults receiving either BCG SSI or BCG Tice at either standard or high dose
1 secondary outcome
Immune response markers
Time frame: Up to 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 22 Jan 2015.
- Derived from this study: PubMed 26450421Minhinnick A, Harris S, Wilkie M, Peter J, Stockdale L, Manjaly-Thomas ZR, Vermaak S, Satti I, Moss P, McShane H. Optimization of a Human Bacille Calmette-Guerin Challenge Model: A Tool to Evaluate Antimycobacterial Immunity. J Infect Dis. 2016 Mar 1;213(5):824-30. doi: 10.1093/infdis/jiv482. Epub 2015 Oct 8.
- Jenner Institute Clinical TrialsLink provided by the sponsor.
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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 study director
University of Oxford
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing BCG SSI and BCG Tice in people with Tuberculosis, run by University of Oxford at 2 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 16 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 22 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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.
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?
Quantity of BCG at challenge site (time frame: At 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 NCT02088892, 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 22 Jan 2015.