TuberculosisPhase 2TESEC-04NCT01241188
A Trial of the C-Tb Skin Test, When Given Intradermally to Adult Patients Recently Diagnosed With Active Tuberculosis (TB)
A Phase 2 study testing C-Tb and 2 TU Tuberculin PPD RT 23 SSI in people with Tuberculosis, run by Statens Serum Institut at 1 site in South Africa.
Trial summary
Tuberculosis (TB) continues to be the most important bacterial infection worldwide and therefore new improved diagnostic tests are needed to help doctors in diagnosing TB. The new skin test is named C-Tb. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- C-Tb and 2 TU Tuberculin PPD RT 23 SSI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 253 participants
- Where
- 1 siteSouth Africa
- Study dates
- Apr 2011to Dec 2011
- Phase
- Phase 2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has signed an informed consent
- Aged 18 to 65 years
- Has been diagnosed with active TB:
- has a compatible clinical picture of TB according to South African guidelines with the intention to treat and at least 1 documented positive sputum smear microscopy result or
- has a compatible clinical picture of TB according to South African Guidelines with the intention to treat and a positive culture result
- Is HIV negative confirmed by 2 two rapid tests (Abbott-DetermineTM HIV-1/2 and Sensa (Seyama Solutions, SA))
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- Is willing and likely to comply with the trial procedures
- Is prepared to grant authorized persons access to their medical record
- Has signed an informed consent
- Aged 18 to 65 years
- Has a compatible clinical picture of TB according to South African guidelines with the intention to treat
- Is HIV positive confirmed by:
- 2 positive rapid tests (Abbott-DetermineTM HIV-1/2 and Sensa (Seyama Solutions, SA)) or
- 1 positive rapid tests (Abbott-DetermineTM HIV-1/2 or Sensa (Seyama Solutions, SA)) and an additional confirmatory ELISA (Enzygnost anti-HIV-1/2 Plus)
- Is willing and likely to comply with the trial procedures
- Is prepared to grant authorized persons access to their medical records
Who cannot join
- Has been in treatment for TB for more than 2 weeks
- Has a known MDR/XDR-TB
- Has within 3 months prior to the day of inclusion been in treatment with a product which is likely to modify the immune response except for HIV treatment (e.g., immunoglobulin, systemic corticosteroids, methotrexate, azathioprine, cyclosporine or blood products)
- Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. MMR, yellow fever, oral typhoid vaccines)
- Has been vaccinated with BCG < 6 months prior to the day of inclusion
- Has been tuberculin (TST) tested < 6 months prior to the day of inclusion
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- Has an active disease affecting the lymphoid organs except for HIV (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)
- Has a current skin condition which interferes with the reading of the skin tests e.g. tattoos, severe scarring, burns/sunburns, rash, eczema, psoriasis, or any other skin disease at or near the injection sites
- Has a condition where blood drawings pose more than minimal risk for the patient, such as haemophilia, other coagulation disorders, or significantly impaired venous access
- Currently participating in another clinical trial with an investigational or non investigational drug or device, or has participated in another clinical trial within the 3 months prior to dosing
- Has participated in previous clinical trials investigating the ESAT-6 and/or CFP-10 antigens
- Is pregnant, breastfeeding or intending to get pregnant
- Has a condition which in the opinion of the investigator is not suitable for participation in the study
Trial locations and contacts
1 site in 1 country.
South Africa1 site
University of Cape Town Lung Institute (Pty) Ltd
Cape Town, Cape Town, 7925
About this study
Official title: A Phase IIb Sensitivity Trial of the Diagnostic Agent C-Tb, When Given Intradermally by the Mantoux Technique to Adult Patients Recently Diagnosed With Active TB
Tuberculosis (TB) continues to be the most important bacterial infection worldwide and therefore new improved diagnostic tests are needed to help doctors in diagnosing TB.
The new skin test is named C-Tb. Like the current Tuberculin Skin Test (TST), the C-Tb test is injected just under the skin and will when positive show a redness and/or swelling at the injection site while a negative test will leave no reactions.
The aim of this trial is to test the C-Tb skin test in adults diagnosed with TB to determine if a TB infected individual has a truly positive test result (this is called to find the sensitivity of the skin test).
Read the detailed description
The trial is designed to investigate the sensitivity of C-Tb using various sizes of cut-off of induration in a double blind randomised, split-body study comparing 0.1 µg/0.1 mL C-Tb with the reference agent 2 T.U. Tuberculin PPD RT23 SSI. (Each volunteer receives the C-Tb agent in one arm and 2 T.U. Tuberculin PPD RT 23 SSI in the other arm). Two groups of adult patients recently diagnosed with active TB will be investigated; patients in the main group will NOT have a co-infection with HIV and patients in the second group will have a co-infection with HIV.
The C-Tb and 2 TU Tuberculin PPD RT 23 SSI agents are given concomitantly to each volunteer in the RIGHT AND LEFT forearms according to a double blind randomisation scheme.
The primary objectives are to assess the sensitivity of the C-Tb test as a function of the cut-off value (i.e., the smallest size of induration measured in mm resulting in a positive outcome of the C-Tb test) when the test is administered intradermally by the Mantoux technique to HIV negative adult patients recently diagnosed with active TB and to assess the sensitivity of the C-Tb test as a function of the cut-off value (i.e., the smallest size of induration measured in mm resulting in a positive outcome of the C-Tb test) when the test is administered intradermally by the Mantoux technique to HIV positive adult patients recently diagnosed with active TB The sensitivity is defined as the relative frequency of patients with an induration response ≥ cut-off in TB patients.
Similarly the specificity of the C-Tb test is defined as the relative frequency of subjects in a healthy population (i.e., no exposure to M. tuberculosis) who have an induration response < cut-off after a C-Tb test.
An optimal cut-off point of being infected will be determined by combing the results from the present sensitivity study with those from a parallel specificity study in (BCG vaccinated) individuals with no previous exposure to M. tuberculosis.
The secondary objectives of the trial is to compare the induration response of C-Tb with the induration response of 2 T.U. Tuberculin PPD RT 23 SSI, to compare the induration response of C-Tb with the in-vitro IFN-γ response measured at screening using the QuantiFERON®-TB Gold In Tube assay, to correlate the induration response to the initial CD4+ counts in HIV positive patients and to record all adverse events (local and systemic) occurring within 28 days after application of the agents
- Conditions
- Tuberculosis
- Being tested
- C-Tb, 2 TU Tuberculin PPD RT 23 SSI
- Keywords
- tuberculosis, rdESAT-6, CFP-10, skin test, diagnostic test
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C-TbBiological
Also called rdESAT-6 + rCFP-10
The C-Tb agent is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearms according to a double blind randomisation scheme
2 TU Tuberculin PPD RT 23 SSIBiological
Also called PPD, Tuberculin
The 2 TU Tuberculin PPD RT 23 SSI agent is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearms according to a double blind randomisation scheme
| Study group | Role | What they receive |
|---|---|---|
| 0.1 µg/0.1 mL C-Tb | Experimental | The C-Tb and 2 TU Tuberculin PPD RT 23 SSI agents are given concomitantly to each volunteer in the RIGHT AND LEFT forearms according to a double blind randomisation scheme Receives: Biological: C-Tb |
| 2 TU Tuberculin PPD RT 23 SSI | Active comparator | The C-Tb and 2 TU Tuberculin PPD RT 23 SSI agents are given concomitantly to each volunteer in the RIGHT AND LEFT forearms according to a double blind randomisation scheme Receives: Biological: 2 TU Tuberculin PPD RT 23 SSI |
What is being measured
The primary outcome is the main question the study is designed to answer.
The diameter of induration at the injection sites measured transversely to the long axis of the forearm 2-3 days after application of the agents
Measured: From injections to 2-3 days after aplication
Secondary outcomes (4)
Injection site adverse reactions within 28 days after application of the agents
Measured: Onset between the injections and 28 days after the injections
All adverse events occurring within 28 days after application of the agents
Measured: Onset between the injections and 28 days after the injections
Laboratory safety parameters of haematology and biochemistry
Measured: Onset between the injections and 28 days after the injections
In vitro IFN-γ response as measured by the QuantiFERON®-TB Gold In Tube assay
Measured: Onset between the injections and 28 days after the injections
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2010 (estimated)
- Study startApr 2011
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 253 participants (actual)
Sponsor and investigators
- Lead sponsor
- Statens Serum Institut
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Birgit Thierry-Carstensen, Study director, Statens Serum Institut DenmarkKeertan Dheda, MD, Principal investigator, University of Cape Town Lung Institute (Pty) Ltd, South Africa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01241188
- Sponsor's protocol ID
- TESEC-04
- Acronym
- TESEC-04
- Status last verified
- Apr 2015
- First submitted
- 15 Nov 2010
- Last updated
- 17 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hoff ST, Peter JG, Theron G, Pascoe M, Tingskov PN, Aggerbeck H, Kolbus D, Ruhwald M, Andersen P, Dheda K. Sensitivity of C-Tb: a novel RD-1-specific skin test for the diagnosis of tuberculosis infection. Eur Respir J. 2016 Mar;47(3):919-28. doi: 10.1183/13993003.01464-2015. Epub 2015 Dec 17.
PubMed 26677940Aggerbeck H, Giemza R, Joshi P, Tingskov PN, Hoff ST, Boyle J, Andersen P, Lewis DJ. Randomised clinical trial investigating the specificity of a novel skin test (C-Tb) for diagnosis of M. tuberculosis infection. PLoS One. 2013 May 14;8(5):e64215. doi: 10.1371/journal.pone.0064215. Print 2013.
PubMed 23691171
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIb Sensitivity Trial of the Diagnostic Agent C-Tb, When Given Intradermally by the Mantoux Technique to Adult Patients Recently Diagnosed With Active TB
- ClinicalTrials.gov ID
- NCT01241188
- Acronym / sponsor ID
- TESEC-04 / TESEC-04
- Conditions
- Tuberculosis
- Keywords
- tuberculosis, rdESAT-6, CFP-10, skin test, diagnostic test
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 253 participants (actual)
- Lead sponsor
- Statens Serum InstitutUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 16 Nov 2010 (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.
Tuberculosis (TB) continues to be the most important bacterial infection worldwide and therefore new improved diagnostic tests are needed to help doctors in diagnosing TB.
The new skin test is named C-Tb. Like the current Tuberculin Skin Test (TST), the C-Tb test is injected just under the skin and will when positive show a redness and/or swelling at the injection site while a negative test will leave no reactions.
The aim of this trial is to test the C-Tb skin test in adults diagnosed with TB to determine if a TB infected individual has a truly positive test result (this is called to find the sensitivity of the skin test).
Detailed description
The trial is designed to investigate the sensitivity of C-Tb using various sizes of cut-off of induration in a double blind randomised, split-body study comparing 0.1 µg/0.1 mL C-Tb with the reference agent 2 T.U. Tuberculin PPD RT23 SSI. (Each volunteer receives the C-Tb agent in one arm and 2 T.U. Tuberculin PPD RT 23 SSI in the other arm). Two groups of adult patients recently diagnosed with active TB will be investigated; patients in the main group will NOT have a co-infection with HIV and patients in the second group will have a co-infection with HIV.
The C-Tb and 2 TU Tuberculin PPD RT 23 SSI agents are given concomitantly to each volunteer in the RIGHT AND LEFT forearms according to a double blind randomisation scheme.
The primary objectives are to assess the sensitivity of the C-Tb test as a function of the cut-off value (i.e., the smallest size of induration measured in mm resulting in a positive outcome of the C-Tb test) when the test is administered intradermally by the Mantoux technique to HIV negative adult patients recently diagnosed with active TB and to assess the sensitivity of the C-Tb test as a function of the cut-off value (i.e., the smallest size of induration measured in mm resulting in a positive outcome of the C-Tb test) when the test is administered intradermally by the Mantoux technique to HIV positive adult patients recently diagnosed with active TB The sensitivity is defined as the relative frequency of patients with an induration response ≥ cut-off in TB patients.
Similarly the specificity of the C-Tb test is defined as the relative frequency of subjects in a healthy population (i.e., no exposure to M. tuberculosis) who have an induration response < cut-off after a C-Tb test.
An optimal cut-off point of being infected will be determined by combing the results from the present sensitivity study with those from a parallel specificity study in (BCG vaccinated) individuals with no previous exposure to M. tuberculosis.
The secondary objectives of the trial is to compare the induration response of C-Tb with the induration response of 2 T.U. Tuberculin PPD RT 23 SSI, to compare the induration response of C-Tb with the in-vitro IFN-γ response measured at screening using the QuantiFERON®-TB Gold In Tube assay, to correlate the induration response to the initial CD4+ counts in HIV positive patients and to record all adverse events (local and systemic) occurring within 28 days after application of the agents
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 0.1 µg/0.1 mL C-Tb | Experimental | Biological: C-TbThe C-Tb and 2 TU Tuberculin PPD RT 23 SSI agents are given concomitantly to each volunteer in the RIGHT AND LEFT forearms according to a double blind randomisation scheme |
| 2 TU Tuberculin PPD RT 23 SSI | Active comparator | Biological: 2 TU Tuberculin PPD RT 23 SSIThe C-Tb and 2 TU Tuberculin PPD RT 23 SSI agents are given concomitantly to each volunteer in the RIGHT AND LEFT forearms according to a double blind randomisation scheme |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Has signed an informed consent
- Aged 18 to 65 years
- Has been diagnosed with active TB:
- Is HIV negative confirmed by 2 two rapid tests (Abbott-DetermineTM HIV-1/2 and Sensa (Seyama Solutions, SA))
- Is willing and likely to comply with the trial procedures
Key exclusion criteria (13 listed)
- Has been in treatment for TB for more than 2 weeks
- Has a known MDR/XDR-TB
- Has within 3 months prior to the day of inclusion been in treatment with a product which is likely to modify the immune response except for HIV treatment (e.g., immunoglobulin, systemic corticosteroids, methotrexate, azathioprine, cyclosporine or blood products)
- Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. MMR, yellow fever, oral typhoid vaccines)
- Has been vaccinated with BCG < 6 months prior to the day of inclusion
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 |
|---|---|---|
| C-TbAlso: rdESAT-6 + rCFP-10The C-Tb agent is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearms according to a double blind randomisation scheme | Biological | 0.1 µg/0.1 mL C-Tb |
| 2 TU Tuberculin PPD RT 23 SSIAlso: PPD, TuberculinThe 2 TU Tuberculin PPD RT 23 SSI agent is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearms according to a double blind randomisation scheme | Biological | 2 TU Tuberculin PPD RT 23 SSI |
Primary outcome
The diameter of induration at the injection sites measured transversely to the long axis of the forearm 2-3 days after application of the agents
Time frame: From injections to 2-3 days after aplication
4 secondary outcomes
Injection site adverse reactions within 28 days after application of the agents
Time frame: Onset between the injections and 28 days after the injections
All adverse events occurring within 28 days after application of the agents
Time frame: Onset between the injections and 28 days after the injections
Laboratory safety parameters of haematology and biochemistry
Time frame: Onset between the injections and 28 days after the injections
In vitro IFN-γ response as measured by the QuantiFERON®-TB Gold In Tube assay
Time frame: Onset between the injections and 28 days after the injections
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 17 Apr 2015.
- Derived from this study: PubMed 26677940Hoff ST, Peter JG, Theron G, Pascoe M, Tingskov PN, Aggerbeck H, Kolbus D, Ruhwald M, Andersen P, Dheda K. Sensitivity of C-Tb: a novel RD-1-specific skin test for the diagnosis of tuberculosis infection. Eur Respir J. 2016 Mar;47(3):919-28. doi: 10.1183/13993003.01464-2015. Epub 2015 Dec 17.
- Derived from this study: PubMed 23691171Aggerbeck H, Giemza R, Joshi P, Tingskov PN, Hoff ST, Boyle J, Andersen P, Lewis DJ. Randomised clinical trial investigating the specificity of a novel skin test (C-Tb) for diagnosis of M. tuberculosis infection. PLoS One. 2013 May 14;8(5):e64215. doi: 10.1371/journal.pone.0064215. Print 2013.
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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.
Birgit Thierry-Carstensen study director
Statens Serum Institut Denmark
Keertan Dheda, MD principal investigator
University of Cape Town Lung Institute (Pty) Ltd, South Africa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing C-Tb and 2 TU Tuberculin PPD RT 23 SSI in people with Tuberculosis, run by Statens Serum Institut at 1 site in South Africa.
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 16 inclusion and 13 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 17 Apr 2015. 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 South Africa. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The diameter of induration at the injection sites measured transversely to the long axis of the forearm 2-3 days after application of the agents (time frame: From injections to 2-3 days after aplication). 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 NCT01241188, which also lists 2 linked publications.
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 17 Apr 2015.