NCT01600963

A Study to Evaluate the Efficacy and Safety of TMC207 in Patients With Pulmonary Infection With Multi-drug Resistant Mycobacterium Tuberculosis

A Phase III Placebo-controlled, Double-blind, Randomized Trial to Evaluate the Efficacy and Safety of TMC207 in Subjects With Sputum Smear-positive Pulmonary Infection With Multi-drug Resistant Mycobacterium Tuberculosis (MDR-TB)

• Status: Withdrawn
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Janssen Infectious Diseases BVBA · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to provide safety and efficacy data for TMC207 and to demonstrate that TMC207 added to a background regimen (BR) is superior to treatment with the BR plus placebo.

Detailed description

This is a randomized (individuals will be assigned by chance to study treatments), double-blind (individual and investigator will not know the identity of study treatments), placebo (substance containing no active medication)-controlled, 2-arm study in patients with sputum smear-positive pulmonary infection with multi-drug resistant tuberculosis (MDR-TB) defined as tuberculosis (TB) due to infection with a strain of Mycobacterium tuberculosis (M. tuberculosis) that is resistant to both isoniazid and rifampin, or pre-extensively drug resistant (pre-XDR-TB) defined as TB due to infection with an MDR strain of M. tuberculosis that is resistant either to at least one of the injectable second-line drugs \[amikacin, kanamycin, or capreomycin\] or to any fluoroquinolone, but not both). Approximately 600 patients with sputum smear-positive pulmonary infection with MDR-TB or pre-XDR TB will receive a background regimen (BR) of MDR-TB therapy and will be randomly assigned in a 1:1 ratio to one of 2 treatment arms (Arms A \[TMC207 + BR\] and B \[placebo + BR\]). All patients will receive TMC207 or placebo in combination with a BR of MDR-TB therapy. TMC207 (or matching placebo) will be taken as oral tablets at a once daily dose of 400 mg for the first 2 weeks and 200 mg 3 times/week for the remaining period of TMC207 (or matching placebo) administration. The study will consist of a screening phase of a maximum of 3 weeks, a 36-week double-blind treatment phase, followed by a 48-week follow-up phase up to Week 84, also referred to as the treatment-free follow-up. After the treatment-free follow-up phase, there will be a safety follow-up phase of 48 weeks up to Week 132. Patients from Arms A or B who fail treatment according to prespecified criteria will be given the option to receive 24 weeks of TMC207 plus an individualized salvage regimen taken for a duration consistent with national TB guidelines. Efficacy and pharmacokinetic evaluations will be performed at time points as detailed in the protocol. Safety will be monitored throughout the study.

Conditions

• Multi-drug Resistant Tuberculosis

Interventions

Type	Name	Description
DRUG	Arm A Double-blind Phase: TMC207	Type=exact number, unit=mg, number=400 mg for the first 2 weeks and 200 mg 3 times per week for the remainder of the treatment period, form=tablet, route=oral administration.
DRUG	Arm B Double-blind Phase: Placebo	Form=tablet, route=oral administration, taken once daily for 2 weeks then 3 times per week for the remainder of the treatment period.
DRUG	Treatment Failure During Double-blind Phase: TMC207	Type=exact number, unit=mg, number=200 mg 3 times per week, form=tablet, route=oral administration.
DRUG	Treatment Failure During Follow-up Phase: TMC207	Type=exact number, unit=mg, number=400 mg once daily for 2 wks and 200mg three times per week for 22 weeks, form=tablet, route=oral administration.

Timeline

• Start date: 2014-03-01
• Primary completion: 2016-07-01
• Completion: 2022-11-01
• First posted: 2012-05-17
• Last updated: 2015-12-02

Locations

44 sites across 17 countries: Brazil, Cambodia, China, Estonia, Ethiopia, Georgia, Latvia, Mexico, Peru, Philippines, Russia, South Africa, South Korea, Taiwan, Thailand, Turkey (Türkiye), Ukraine