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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
208
TMC207 400mg (4 tablets) once daily for 14 days, 200mg (2 tablets) three times a week for 6 or 22 weeks.
Placebo 4 tablets once daily for 14 days, 2 tablets three times a week for 6 or 22 weeks.
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.
Unnamed facility
Rio de Janeiro, Brazil
Unnamed facility
Chennai, India
Unnamed facility
New Delhi, India
Unnamed facility
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.
Time frame: 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.
Time frame: Week 24, Stage 2
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.
Time frame: Week 24, Stage 1
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.
Time frame: Week 72, Stage 2
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Stopinu Region, Latvia
Unnamed facility
Lima, Peru
Unnamed facility
Quezon City, Philippines
Unnamed facility
Moscow, Russia
Unnamed facility
Bethelsdorp, South Africa
Unnamed facility
Cape Town, South Africa
Unnamed facility
Durban, South Africa
...and 6 more locations
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.
Time frame: Week 8, 24, and 104 (Stage 1)
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.
Time frame: Week 24, Week 72, and Week 120 (Stage 2)