TuberculosisPhase 2NCT00910871
To Evaluate the Safety, Tolerability, and Efficacy of TMC207 as Part of an Individualized Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Participants With Sputum Smear-positive Pulmonary MDR-TB.
A Phase 2 study testing TMC207 and Background Regimen (BR) for MDR-TB in people with Tuberculosis, run by Janssen Infectious Diseases BVBA at 27 sites in 12 countries.
Trial summary
The purpose of this study is to evaluate the safety, tolerability and effectiveness of TMC207 in combination with an individualized background regimen (BR) of antibacterial drugs as treatment for MDR-TB Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis
- What is being tested?
- TMC207 and Background Regimen (BR) for MDR-TB
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 241 participants
- Where
- 27 sitesin 12 countries
- Study dates
- Sep 2009to Jan 2013
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Females of child-bearing potential must be using and are willing to continue using effective birth control methods, or be willing to practice sexual abstinence throughout treatment or be nonheterosexual active
- Confirmed pulmonary MDR-TB infection including those infected with XDR (extensively drug resistant)-TB
- Positive for acid-fast bacilli (AFB) on direct smear examination of expectorated sputum specimen (= 1+ smear-positive)
- HIV-positive patients are eligible, provided they meet the requirements as described in the protocol
- Must voluntarily sign the Informed Consent Form (ICF) prior to starting any study activities
- Willing to comply with protocol requirements
- Willing to comply with NTP treatment guidelines
Who cannot join
- Patients having a known or suspected hypersensitivity or serious adverse reaction to TMC207
- Patients with significant cardiac arrhythmia requiring medication
- Patients with complicated or severe extrapulmonary manifestations of TB, including central nervous system infection
- Patients with certain QT/QTc interval characteristics as described in the protocol
- Patients having participated in other clinical studies with investigational agents, within 8 weeks prior to trial start
- Women who are pregnant or breastfeeding
- Patients who have previously received treatment with TMC207 as part of a clinical trial.
Trial locations and contacts
27 sites in 12 countries.
27 sites in 12 countries
China5 sites
Study site
Beijing
Study site
Fuzhou
Study site
Jinan
Study site
Nanjing
Study site
Shanghai
South Africa3 sites
Study site
Bellville West Cape
Study site
Durban
Study site
Sandringham
About this study
Official title: A Phase II, Open-label Trial With TMC207 as Part of a Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Subjects With Sputum Smear-positive Pulmonary Infection With MDR-TB.
The purpose of this study is to evaluate the safety, tolerability and effectiveness of TMC207 in combination with an individualized background regimen (BR) of antibacterial drugs as treatment for MDR-TB
Read the detailed description
This is a Phase II, open-label (all people involved know the identity of the intervention) trial to evaluate the safety, tolerability, and efficacy of TMC207 as part of an individualized Multi-drug Resistant Tuberculosis (MDR-TB) treatment regimen in participants with sputum smear-positive pulmonary MDR-TB. Approximately 225 participants will receive TMC207 for 24 weeks in combination with an individualized background regimen (BR) of antibacterial drugs used in the treatment of TB according to national and international guidelines and selected at the baseline visit. TMC207 dosage will be 400 mg once daily (q.d.) for the first 2 weeks and 200 mg 3 times/week (t.i.w.) for the following 22 weeks. Upon completion of the 24-week treatment with TMC207, all participants will continue to receive their BR under the care of their physician and in accordance with national TB program (NTP) treatment guidelines.
Additionally, the pharmacokinetics (how the body absorbs, distributes, metabolizes and eliminates a drug) of TMC207 and its N-monodesmethyl metabolite (M2), and pharmacokinetic/pharmacodynamic (the study of the action or effects a drug has on the body) relationships for safety and efficacy will be assessed. Safety evaluations that will be performed are lab tests, vital signs, ECG, reporting of adverse events, physical examinations and X-rays.
All participants will be followed up for 19 months after their last intake of TMC207. Also participants who prematurely withdraw (unless they withdraw consent) will be followed for this period or until the last follow-up visit for the last patient in the trial. Investigators will be asked to provide information about the survival/clinical outcome of these participants throughout the follow-up period, approximately every 6 months.
Primary outcome is time to sputum culture conversion in Mycobacteria Growth Indicator Tube (MGIT) during and beyond treatment with TMC207. Sputum culture conversion will be defined as 2 consecutive negative cultures from sputa collected at least 28 days apart.
- Conditions
- Tuberculosis
- Being tested
- TMC207, Background Regimen (BR) for MDR-TB
- Keywords
- Tuberculosis, TMC207-TiDP13-C209, TMC207-C209, TMC207, TB, MDR-TB
- Medical subject headings
- Tuberculosis, Tuberculosis, Multidrug-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMC207Drug
TMC207 400mg once daily for 2 weeks then 200mg three times a week for 22 weeks.
Background Regimen (BR) for MDR-TBDrug
Background Regimen (BR) of antibacterial drugs used in the treatment of TB according to national TB program and selected at the baseline visit as specified in the protocol for up to 96 weeks.
| Study group | Role | What they receive |
|---|---|---|
| TMC207 | Experimental | TMC207 400mg once daily for 2 weeks then 200mg three times a week for 22 weeks in addition to Background Regimen (BR) for the treatment of multi-drug resistant tuberculosis (MDR-TB). Receives: Drug: TMC207; Drug: Background Regimen (BR) for MDR-TB |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Median Time to Sputum Culture Conversion
The table below shows the median time in days to culture conversion for the modified intent-to-treat (mITT) population up to Week 24. Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multi-drug resistant tuberculosis (MDR-TB) taken at least 25 days apart. Participants who discontinued during the 24-week period were considered non-responders (based on Mycobacteria Growth Indicator Tube [MGIT]).
Measured: Up to Week 24
Secondary outcomes (1)
The Percentage of Participants With Sputum Culture Conversion
The table below shows the percentage of participants who were responders to treatment. Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multi-drug resistant tuberculosis (MDR-TB) taken at least 25 days apart. Participants who discontinued or died during the trial were considered non-responders.
Measured: Week 120
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2009 (estimated)
- Study startSep 2009
- Primary completionMar 2011
- Study completionJan 2013
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 (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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 241 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Infectious Diseases BVBA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Infectious Diseases BVBA Clinical Trial, Study director, Janssen Infectious Diseases BVBA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00910871
- Sponsor's protocol ID
- CR012352
- Other IDs
- TMC207-TiDP13-C209, 2008-008444-25, 2008
- Status last verified
- Apr 2015
- First submitted
- 28 May 2009
- Last updated
- 24 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bolhuis MS, Akkerman OW, Sturkenboom MGG, van Boven JFM, Alffenaar JC, Stevens J. Bedaquiline exposure in people with drug-resistant TB treated for diabetes: analysis of two phase 2 trials. Int J Tuberc Lung Dis. 2023 Apr 1;27(4):335-337. doi: 10.5588/ijtld.22.0581. No abstract available.
PubMed 37035978Pym AS, Diacon AH, Tang SJ, Conradie F, Danilovits M, Chuchottaworn C, Vasilyeva I, Andries K, Bakare N, De Marez T, Haxaire-Theeuwes M, Lounis N, Meyvisch P, Van Baelen B, van Heeswijk RP, Dannemann B; TMC207-C209 Study Group. Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis. Eur Respir J. 2016 Feb;47(2):564-74. doi: 10.1183/13993003.00724-2015. Epub 2015 Dec 2.
PubMed 26647431
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open-label Trial With TMC207 as Part of a Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Subjects With Sputum Smear-positive Pulmonary Infection With MDR-TB.
- ClinicalTrials.gov ID
- NCT00910871
- Acronym / sponsor ID
- CR012352
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, TMC207-TiDP13-C209, TMC207-C209, TMC207, TB, MDR-TB
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 241 participants (actual)
- Lead sponsor
- Janssen Infectious Diseases BVBAIndustry (pharma, biotech, devices)
- Study start
- Sep 2009
- Primary completion
- Mar 2011 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 1 Jun 2009 (estimated)
- Results
- Posted 16 May 2013
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 safety, tolerability and effectiveness of TMC207 in combination with an individualized background regimen (BR) of antibacterial drugs as treatment for MDR-TB
Detailed description
This is a Phase II, open-label (all people involved know the identity of the intervention) trial to evaluate the safety, tolerability, and efficacy of TMC207 as part of an individualized Multi-drug Resistant Tuberculosis (MDR-TB) treatment regimen in participants with sputum smear-positive pulmonary MDR-TB. Approximately 225 participants will receive TMC207 for 24 weeks in combination with an individualized background regimen (BR) of antibacterial drugs used in the treatment of TB according to national and international guidelines and selected at the baseline visit. TMC207 dosage will be 400 mg once daily (q.d.) for the first 2 weeks and 200 mg 3 times/week (t.i.w.) for the following 22 weeks. Upon completion of the 24-week treatment with TMC207, all participants will continue to receive their BR under the care of their physician and in accordance with national TB program (NTP) treatment guidelines.
Additionally, the pharmacokinetics (how the body absorbs, distributes, metabolizes and eliminates a drug) of TMC207 and its N-monodesmethyl metabolite (M2), and pharmacokinetic/pharmacodynamic (the study of the action or effects a drug has on the body) relationships for safety and efficacy will be assessed. Safety evaluations that will be performed are lab tests, vital signs, ECG, reporting of adverse events, physical examinations and X-rays.
All participants will be followed up for 19 months after their last intake of TMC207. Also participants who prematurely withdraw (unless they withdraw consent) will be followed for this period or until the last follow-up visit for the last patient in the trial. Investigators will be asked to provide information about the survival/clinical outcome of these participants throughout the follow-up period, approximately every 6 months.
Primary outcome is time to sputum culture conversion in Mycobacteria Growth Indicator Tube (MGIT) during and beyond treatment with TMC207. Sputum culture conversion will be defined as 2 consecutive negative cultures from sputa collected at least 28 days apart.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TMC207 | Experimental | Drug: TMC207, Drug: Background Regimen (BR) for MDR-TBTMC207 400mg once daily for 2 weeks then 200mg three times a week for 22 weeks in addition to Background Regimen (BR) for the treatment of multi-drug resistant tuberculosis (MDR-TB). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Females of child-bearing potential must be using and are willing to continue using effective birth control methods, or be willing to practice sexual abstinence throughout treatment or be nonheterosexual active
- Confirmed pulmonary MDR-TB infection including those infected with XDR (extensively drug resistant)-TB
- Positive for acid-fast bacilli (AFB) on direct smear examination of expectorated sputum specimen (= 1+ smear-positive)
- HIV-positive patients are eligible, provided they meet the requirements as described in the protocol
- Must voluntarily sign the Informed Consent Form (ICF) prior to starting any study activities
Key exclusion criteria (7 listed)
- Patients having a known or suspected hypersensitivity or serious adverse reaction to TMC207
- Patients with significant cardiac arrhythmia requiring medication
- Patients with complicated or severe extrapulmonary manifestations of TB, including central nervous system infection
- Patients with certain QT/QTc interval characteristics as described in the protocol
- Patients having participated in other clinical studies with investigational agents, within 8 weeks prior to trial start
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 |
|---|---|---|
| TMC207TMC207 400mg once daily for 2 weeks then 200mg three times a week for 22 weeks. | Drug | TMC207 |
| Background Regimen (BR) for MDR-TBBackground Regimen (BR) of antibacterial drugs used in the treatment of TB according to national TB program and selected at the baseline visit as specified in the protocol for up to 96 weeks. | Drug | TMC207 |
Primary outcome
The Median Time to Sputum Culture Conversion
Time frame: Up to Week 24
The table below shows the median time in days to culture conversion for the modified intent-to-treat (mITT) population up to Week 24. Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multi-drug resistant tuberculosis (MDR-TB) taken at least 25 days apart. Participants who discontinued during the 24-week period were considered non-responders (based on Mycobacteria Growth Indicator Tube [MGIT]).
1 secondary outcome
The Percentage of Participants With Sputum Culture Conversion
Time frame: Week 120
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37035978Bolhuis MS, Akkerman OW, Sturkenboom MGG, van Boven JFM, Alffenaar JC, Stevens J. Bedaquiline exposure in people with drug-resistant TB treated for diabetes: analysis of two phase 2 trials. Int J Tuberc Lung Dis. 2023 Apr 1;27(4):335-337. doi: 10.5588/ijtld.22.0581. No abstract available.
- Derived from this study: PubMed 26647431Pym AS, Diacon AH, Tang SJ, Conradie F, Danilovits M, Chuchottaworn C, Vasilyeva I, Andries K, Bakare N, De Marez T, Haxaire-Theeuwes M, Lounis N, Meyvisch P, Van Baelen B, van Heeswijk RP, Dannemann B; TMC207-C209 Study Group. Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis. Eur Respir J. 2016 Feb;47(2):564-74. doi: 10.1183/13993003.00724-2015. Epub 2015 Dec 2.
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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.
Janssen Infectious Diseases BVBA Clinical Trial study director
Janssen Infectious Diseases BVBA
27 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TMC207 and Background Regimen (BR) for MDR-TB in people with Tuberculosis, run by Janssen Infectious Diseases BVBA at 27 sites in 12 countries.
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 7 inclusion and 7 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 24 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 27 sites in China, Russia, South Africa, Ukraine, Estonia and 7 more countries. 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?
Yes. Results are posted in the registry (first posted 16 May 2013). 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?
The Median Time to Sputum Culture Conversion (time frame: Up to Week 24). 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 NCT00910871, 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 24 Apr 2015.