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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 2

Conditions: Tuberculosis

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT00449644

CR011929

2007-004462-40 (EudraCT Number)

TMC207-TIDP13-C208 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 208 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

208 participants in 4 patient groups, including a placebo group

TMC207 Stage 1

Experimental group

Description:

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).

Treatment:

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

Drug: TMC207

Placebo Stage 1

Placebo Comparator group

Description:

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

Treatment:

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

Drug: Placebo

TMC207 Stage 2

Experimental group

Description:

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.

Treatment:

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

Drug: TMC207

Placebo Stage 2

Placebo Comparator group

Description:

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

Treatment:

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

Drug: Placebo