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

NCT ID: NCT01600963

Last Updated: 2015-12-02

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2022-11-30

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm A

Group Type: EXPERIMENTAL

Arm A Double-blind Phase: TMC207

Intervention Type: DRUG

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.

Treatment Failure During Double-blind Phase: TMC207

Intervention Type: DRUG

Type=exact number, unit=mg, number=200 mg 3 times per week, form=tablet, route=oral administration.

Treatment Failure During Follow-up Phase: TMC207

Intervention Type: DRUG

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.

Arm B

Group Type: PLACEBO_COMPARATOR

Arm B Double-blind Phase: Placebo

Intervention Type: DRUG

Form=tablet, route=oral administration, taken once daily for 2 weeks then 3 times per week for the remainder of the treatment period.

Treatment Failure During Double-blind Phase: TMC207

Intervention Type: DRUG

Type=exact number, unit=mg, number=200 mg 3 times per week, form=tablet, route=oral administration.

Treatment Failure During Follow-up Phase: TMC207

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosed with sputum smear-positive pulmonary Mycobacterium multi-drug resistant tuberculosis; including pre-extensively drug resistant TB, and positive for acid fast bacilli on direct smear examination of expectorated or induced sputum specimen (>=1+ smear positive within the preceding 3 weeks) at screening and also on Day -1

Exclusion Criteria

• Has known infection with extensively drug resistant tuberculosis isolate
• Has a clinically significant active medical condition such as, but not limited to, hepatic, pancreatic, renal, cardiovascular, gastrointestinal, hematologic, neurologic, locomotor, immunologic, ophthalmologic (e.g., corneal opacification or ulcers, uveitis, chorioretinitis), metabolic (except stable diabetes based on the investigator's judgement), endocrine, oncological disease, muscular disease (e.g., myositis, rhabdomyolysis), or psychiatric, dermatological illness, or any other illness that the investigator considers should exclude the patient or that could interfere with the interpretation of the study results. Eligibility of patients with poorly controlled diabetes as indicated by hemoglobin A1c higher than the normal range at screening should be based on the investigators judgment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Infectious Diseases BVBA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Infectious Diseases BVBA Clinical Trial

Role: STUDY_DIRECTOR

Janssen Infectious Diseases BVBA

Locations

Porto Alegre, , Brazil

Rio de Janeiro, , Brazil

São Paulo, , Brazil

Phnom Penh, , Cambodia

Beijing, , China

Changsha, , China

Chongqing, , China

Fuzhou, , China

Jinan, , China

Nanjing, , China

Shanghai, , China

Kohtla-Järve, , Estonia

Talinn, , Estonia

Addis Ababa, , Ethiopia

Gonder, , Ethiopia

Tbilisi, , Georgia

Stopinu Region, , Latvia

Monterrey, , Mexico

Lima, , Peru

Quezon City, , Philippines

Arkhangelsk, , Russia

Moscow, , Russia

Novosibirsk, , Russia

Oryol, , Russia

Saint Petersburg, , Russia

Yekaterinburg, , Russia

Paarl, , South Africa

Sandringham, , South Africa

Ysterplaat, , South Africa

Busan, , South Korea

Daegu, , South Korea

Gwangju, , South Korea

Gyeongsangnam-Do, , South Korea

Incheon, , South Korea

Seoul, , South Korea

Changhua County, , Taiwan

New Taipei City, , Taiwan

Taichung, , Taiwan

Tainan City, , Taiwan

Nonthaburi, , Thailand

Keçiören, , Turkey (Türkiye)

Donetsk, , Ukraine

Kiev, , Ukraine

Ternopil, , Ukraine

Countries

Brazil; Cambodia; China; Estonia; Ethiopia; Georgia; Latvia; Mexico; Peru; Philippines; Russia; South Africa; South Korea; Taiwan; Thailand; Turkey (Türkiye); Ukraine

Other Identifiers

TMC207-TIDP13-C210

Identifier Type: OTHER

Identifier Source: secondary_id

2011-000653-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1135-7013

Identifier Type: OTHER

Identifier Source: secondary_id

CR100807

Identifier Type: -

Identifier Source: org_study_id