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

NCT00449644 | Completed Phase 2 Results DMC

• 3 other identifiers: CR011929TMC207-TIDP13-C2082007-004462-40
• Study Type: interventional
• Target: 208
• Locations: 8 countries
• Sites: 16

Brief 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.

Conditions

Tuberculosis

Keywords

Tuberculosis; MDR TB

Outcome Measures

Primary Outcomes (2)

• 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.

  Week 8, Stage 1

• 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.

  Week 24, Stage 2

Secondary Outcomes (4)

• The Time to Sputum Culture Conversion at Week 24 (Stage 1)

  Week 24, Stage 1

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

  Week 72, Stage 2

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

  Week 8, 24, and 104 (Stage 1)

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

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

Study Arms (4)

TMC207 Stage 1

EXPERIMENTAL

TMC207 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).

Drug: TMC207; Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)

Placebo Stage 1

PLACEBO COMPARATOR

Placebo 4 tablets once daily for 14 days, 2 tablets three times a week for 6 weeks in addition to BR for MDR-TB.

Drug: Placebo; Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)

TMC207 Stage 2

EXPERIMENTAL

TMC207 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.

Drug: TMC207; Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)

Placebo Stage 2

PLACEBO COMPARATOR

Placebo 4 tablets once daily for 14 days, 2 tablets three times a week for 22 weeks in addition to BR for MDR-TB.

Drug: Placebo; Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)

Interventions

TMC207 DRUG

TMC207 400mg (4 tablets) once daily for 14 days, 200mg (2 tablets) three times a week for 6 or 22 weeks.

TMC207 Stage 1; TMC207 Stage 2

Placebo DRUG

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

Placebo Stage 1; Placebo Stage 2

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.

Placebo Stage 1; Placebo Stage 2; TMC207 Stage 1; TMC207 Stage 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Janssen Infectious Diseases BVBA: lead

Study Sites (16)

Unknown Facility

Rio de Janeiro, Brazil

Location

Unknown Facility

Chennai, India

Location

Unknown Facility

New Delhi, India

Location

Unknown Facility

Stopinu Region, Latvia

Location

Unknown Facility

Lima, Peru

Location

Unknown Facility

Quezon City, Philippines

Location

Unknown Facility

Moscow, Russia

Location

Unknown Facility

Bethelsdorp, South Africa

Location

Unknown Facility

Cape Town, South Africa

Location

Unknown Facility

Durban, South Africa

Location

Unknown Facility

George, South Africa

Location

Unknown Facility

Klerksdorp, South Africa

Location

Unknown Facility

Sandringham, South Africa

Location

Unknown Facility

Chiang Mai, Thailand

Location

Unknown Facility

Nakhon, Thailand

Location

Unknown Facility

Nonthaburi, Thailand

Location

Related Publications (5)

• 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.

  PMID: 19494215 RESULT

• 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.

  PMID: 37035978 DERIVED

• 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.

  PMID: 30024924 DERIVED

• 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.

  PMID: 26647431 DERIVED

• 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.

  PMID: 25140958 DERIVED

MeSH Terms

Conditions

Tuberculosis; Tuberculosis, Multidrug-Resistant

Interventions

bedaquiline

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Limitations and Caveats

In Participant Flow, deaths occurring during the trial are reported. In addition, 1 TMC207 and 2 placebo subjects in stage 1 and 4 TMC207 and 1 placebo subject in stage 2 died after discontinuation during long-term survival follow-up.

Results Point of Contact

• Title: Medical Leader
• Organization: Janssen Infectious Diseases - Diagnostics BVBA

1 609 730-7768

Study Officials

• Janssen Infectious Diseases BVBA Clinical Trial

  Janssen Infectious Diseases BVBA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2007
• First Posted: March 20, 2007
• Study Start: June 1, 2007
• Primary Completion: March 1, 2010
• Study Completion: October 1, 2012
• Last Updated: April 29, 2014
• Results First Posted: June 25, 2013

Record last verified: 2014-04

Locations

LA (1); ZA (6); BR (1); TH (3); RU (1); IN (2); PE (1); PH (1)