AzTrials
AzTrials

TuberculosisPhase 2NCT00449644

TMC207-TiDP13-C208: Anti-bacterial Activity, Safety, and Tolerability of TMC207 in Participants With Multi-drug Resistant Mycobacterium Tuberculosis (MDR-TB).

A Phase 2 study testing TMC207 and Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis) in people with Tuberculosis, run by Janssen Infectious Diseases BVBA at 16 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The objective of this study is to demonstrate that the antibacterial activity of TMC207 is better than placebo when added to a standardized Background Regimen (BR) for treatment of multi-drug resistant TB. Also safety and tolerability will be evaluated. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Tuberculosis
What is being tested?
TMC207 and Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
208 participants
Where
16 sitesin 8 countries
Study dates
Jun 2007to Oct 2012
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 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Females of non-childbearing potential
  • Patients with newly diagnosed sputum smear-positive pulmonary MDR-TB infection
  • Patients must consent to HIV-testing
  • Patients must be willing to discontinue all TB drugs to allow 7 days washout
  • Patients having normal weight
  • Patients are willing to be hospitalized per standard of care.

Who cannot join

  • Previously having been treated for MDR-TB
  • Having a significant cardiac arrhythmia that requires medication
  • For HIV infected patients, having a CD4+ count < 300 cells/µL
  • Patients with complicated or severe extrapulmonary manifestations of TB or neurological manifestations of TB
  • Patients who will require surgical procedure for management of their TB
  • Evidence of chorioretinitis, optic neuritis, or uveitis at screening
  • Having had a drug susceptibility test performed prior to screening and being not susceptible to at least 3 of the 5 classes of TB drugs used to treat MDR-TB
  • Women who are pregnant and/or breastfeeding.

Trial locations and contacts

16 sites in 8 countries.

16 sites in 8 countries

South Africa6 sites
  • Study site

    Bethelsdorp

  • Study site

    Cape Town

  • Study site

    Durban

  • Study site

    George

  • Study site

    Klerksdorp

  • Study site

    Sandringham

Other trials in South Africa

Thailand3 sites
  • Study site

    Chiang Mai

  • Study site

    Nakhon

  • Study site

    Nonthaburi

Other trials in Thailand

India2 sites
  • Study site

    Chennai

  • Study site

    New Delhi

Other trials in India

Brazil1 site
  • Study site

    Rio de Janeiro

Other trials in Brazil

Latvia1 site
  • Study site

    Stopinu Region

Other trials in Latvia

Peru1 site
  • Study site

    Lima

Other trials in Peru

Philippines1 site
  • Study site

    Quezon City

Other trials in Philippines

Russia1 site
  • Study site

    Moscow

Other trials in Russia

About this study

Official title: A Phase II, Placebo-controlled, Double-blind, Randomized Trial to Evaluate the Anti-bacterial Activity, Safety, and Tolerability of TMC207 in Subjects With Newly Diagnosed Sputum Smear-positive Pulmonary Infection With Multi-drug Resistant Mycobacterium Tuberculosis (MDR-TB).

The objective of this study is to demonstrate that the antibacterial activity of TMC207 is better than placebo when added to a standardized Background Regimen (BR) for treatment of multi-drug resistant TB. Also safety and tolerability will be evaluated.

Read the detailed description

The trial will be conducted in 2 consecutive stages, an exploratory (investigative) stage (Stage 1) and a proof of effectiveness stage (Stage 2). During Stage 1, a panel of 50 participants will be randomized (participants are assigned different treatments based on chance) to receive either TMC207 or placebo for 8 weeks on top of a BR. In Stage 2, another panel of 150 participants will be randomized to receive either TMC207 or placebo for 24 weeks on top of a BR. TMC207 will be dosed as 400 mg every day for the first 2 weeks, and as 200 mg 3 times/week for the following 6 or 22 weeks during Stages 1 and 2, respectively. When the participants in Stage 1 have completed 8 weeks double-blind (neither theparticipant nor the physician knows whether drug or placebo is being taken, or at what dosage) treatment with TMC207 or placebo (or have discontinued earlier), the primary Stage 1 analysis will be performed on all data of the first 8 weeks of treatment. Following this Stage 1 analysis, Stage 2 will be initiated and a panel of 150 new participants will be enrolled. After the double-blind treatment phase in both Stage 1 and Stage 2, participants will continue to receive MDR-TB treatment as per national treatment guidelines. They will be followed for safety, tolerability, pharmacokinetics, and microbiological efficacy for 96 weeks after receiving their last dose of TMC207 or placebo. The Data Safety Monitoring Board Committee will review these data on a regular basis. The DSMB/DSMC is a group of experts in tuberculosis and clinical trial conduct who have no commercial interests in the development of TMC207 and the company (Tibotec, BVBA) that is developing the new TB drug.

Conditions
Tuberculosis
Being tested
TMC207, Placebo, Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)
Keywords
Tuberculosis, 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 (4 tablets) once daily for 14 days, 200mg (2 tablets) three times a week for 6 or 22 weeks.

  • PlaceboDrug

    Placebo 4 tablets once daily for 14 days, 2 tablets three times a week for 6 or 22 weeks.

  • Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)Drug

    Background Regimen (BR) of antibacterial drugs used in the treatment of TB according to national TB program and selected at the baseline visit as speciified in the protocol for up to 96 weeks.

Study groups in NCT00449644
Study groupRoleWhat they receive
TMC207 Stage 1ExperimentalTMC207 400mg (4 tablets) once daily for 14 days, 200mg (2 tablets) three times a week for 6 weeks in addition to Background Regimen (BR) for multi-drug resistant tuberculosis (MDR-TB).
Receives: Drug: TMC207; Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)
Placebo Stage 1Placebo comparatorPlacebo 4 tablets once daily for 14 days, 2 tablets three times a week for 6 weeks in addition to BR for MDR-TB.
Receives: Drug: Placebo; Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)
TMC207 Stage 2ExperimentalTMC207 400mg (4 tablets) once daily for 14 days, 200mg (2 tablets) three times a week for 22 weeks in addition to BR for MDR-TB.
Receives: Drug: TMC207; Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)
Placebo Stage 2Placebo comparatorPlacebo 4 tablets once daily for 14 days, 2 tablets three times a week for 22 weeks in addition to BR for MDR-TB.
Receives: Drug: Placebo; Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Time to Sputum Culture Conversion at Week 8 (Stage 1)

    The table below shows the time to sputum culture conversion. Sputum culture conversion is defined as as having 2 consecutive negative cultures at least 25 days apart, not followed by a confirmed positive during the considered time period. Participants who discontinue or die during the considered time period are considered as non-responders and censored at their last assessment.

    Measured: Week 8, Stage 1

  2. The Time to Sputum Culture Conversion at Week 24 (Stage 2)

    The table below shows the time to sputum culture conversion. Sputum culture conversion is defined as as having 2 consecutive negative cultures at least 25 days apart, not followed by a confirmed positive during the considered time period. Participants who discontinue or die during the considered time period are considered as non-responders and censored at their last assessment.

    Measured: Week 24, Stage 2

Secondary outcomes (4)
  1. The Time to Sputum Culture Conversion at Week 24 (Stage 1)

    The table below shows the time to sputum culture conversion. Sputum culture conversion is defined as as having 2 consecutive negative cultures at least 25 days apart, not followed by a confirmed positive during the considered time period. Participants who discontinue or die during the considered time period are considered as non-responders and censored at their last assessment.

    Measured: Week 24, Stage 1

  2. The Time to Sputum Culture Conversion at Week 72 (Stage 2)

    The table below shows the time to sputum culture conversion. Sputum culture conversion is defined as as having 2 consecutive negative cultures at least 25 days apart, not followed by a confirmed positive during the considered time period. Participants who discontinue or die during the considered time period are considered as non-responders and censored at their last assessment.

    Measured: Week 72, Stage 2

  3. The Percentage of Participants With Sputum Culture Conversion (Stage 1)

    The table below shows the percentage of participants in Stage 1 who were responders to treatment. Sputum culture conversion is defined as as having 2 consecutive negative cultures at least 25 days apart, not followed by a confirmed positive during the considered time period. Participants who discontinue or die during the considered time period are considered as non-responders.

    Measured: Week 8, 24, and 104 (Stage 1)

  4. The Percentage of Participants With Sputum Culture Conversion (Stage 2)

    The table below shows the percentage of participants in Stage 2 who were responders to treatment. Sputum culture conversion is defined as as having 2 consecutive negative cultures at least 25 days apart, not followed by a confirmed positive during the considered time period. Participants who discontinue or die during the considered time period are considered as non-responders.

    Measured: Week 24, Week 72, and Week 120 (Stage 2)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2007 (estimated)
  2. Study startJun 2007
  3. Primary completionMar 2010
  4. Study completionOct 2012

Resources

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
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
208 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00449644
Sponsor's protocol ID
CR011929
Other IDs
TMC207-TIDP13-C208, 2007-004462-40
Status last verified
Apr 2014
First submitted
16 Mar 2007
Last updated
29 Apr 2014
Data monitoring committee
Yes

Publications

  • Diacon AH, Pym A, Grobusch M, Patientia R, Rustomjee R, Page-Shipp L, Pistorius C, Krause R, Bogoshi M, Churchyard G, Venter A, Allen J, Palomino JC, De Marez T, van Heeswijk RP, Lounis N, Meyvisch P, Verbeeck J, Parys W, de Beule K, Andries K, Mc Neeley DF. The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med. 2009 Jun 4;360(23):2397-405. doi: 10.1056/NEJMoa0808427.

    PubMed 19494215
  • 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 37035978
  • Meyvisch P, Kambili C, Andries K, Lounis N, Theeuwes M, Dannemann B, Vandebosch A, Van der Elst W, Molenberghs G, Alonso A. Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial. PLoS One. 2018 Jul 19;13(7):e0200539. doi: 10.1371/journal.pone.0200539. eCollection 2018.

    PubMed 30024924
  • Pym 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
  • Diacon AH, Pym A, Grobusch MP, de los Rios JM, Gotuzzo E, Vasilyeva I, Leimane V, Andries K, Bakare N, De Marez T, Haxaire-Theeuwes M, Lounis N, Meyvisch P, De Paepe E, van Heeswijk RP, Dannemann B; TMC207-C208 Study Group. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N Engl J Med. 2014 Aug 21;371(8):723-32. doi: 10.1056/NEJMoa1313865.

    PubMed 25140958

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TMC207 and Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis) in people with Tuberculosis, run by Janssen Infectious Diseases BVBA at 16 sites in 8 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 6 inclusion and 8 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 29 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in South Africa, Thailand, India, Brazil, Latvia and 3 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. Some participants in this study may receive a placebo. 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 25 Jun 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 Time to Sputum Culture Conversion at Week 8 (Stage 1) (time frame: Week 8, Stage 1). The study lists 2 primary outcomes in all. 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 NCT00449644, which also lists 5 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 29 Apr 2014.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in