- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01600963
A Study to Evaluate the Efficacy and Safety of TMC207 in Patients With Pulmonary Infection With Multi-drug Resistant Mycobacterium Tuberculosis
November 30, 2015 updated by: Janssen Infectious Diseases BVBA
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)
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.
Study Overview
Status
Withdrawn
Conditions
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.
Study Type
Interventional
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Porto Alegre, Brazil
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Rio De Janeiro, Brazil
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Sao Paulo, Brazil
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Phnom Penh, Cambodia
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Beijing, China
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Changsha, China
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Chongqing, China
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Fuzhou, China
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Jinan, China
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Nanjing, China
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Shanghai, China
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Kohtla-Järve, Estonia
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Talinn, Estonia
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Addis Ababa, Ethiopia
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Gondar, Ethiopia
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Tbilisi, Georgia
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Busan, Korea, Republic of
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Daegu, Korea, Republic of
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Gwangju, Korea, Republic of
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Gyeongsangnam-Do, Korea, Republic of
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Incheon, Korea, Republic of
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Seoul, Korea, Republic of
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Stopinu Region, Latvia
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Monterrey, Mexico
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Lima, Peru
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Quezon City, Philippines
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Arkhangelsk, Russian Federation
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Ekaterinburg, Russian Federation
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Moscow, Russian Federation
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Novosibirsk, Russian Federation
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Orel, Russian Federation
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Saint-Petersburg, Russian Federation
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Paarl, South Africa
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Sandringham, South Africa
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Ysterplaat, South Africa
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Changhua County, Taiwan
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New Taipei City, Taiwan
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Taichung, Taiwan
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Tainan, Taiwan
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Nonthaburi, Thailand
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Kecioren, Turkey
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Donetsk, Ukraine
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Kiev, Ukraine
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Ternopil, Ukraine
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Arm A
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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.
Type=exact number, unit=mg, number=200 mg 3 times per week, form=tablet, route=oral administration.
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.
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Placebo Comparator: Arm B
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Type=exact number, unit=mg, number=200 mg 3 times per week, form=tablet, route=oral administration.
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.
Form=tablet, route=oral administration, taken once daily for 2 weeks then 3 times per week for the remainder of the treatment period.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Number of patients with favorable treatment outcome at Week 60
Time Frame: Week 60
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Week 60
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of patients with confirmed culture conversion at Week 84
Time Frame: Week 84
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Week 84
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Number of patients with confirmed culture conversion at Week 60 or at time of trial discontinuation
Time Frame: Up to Week 132
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Up to Week 132
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The number of patients with development of pre-extensively drug-resistant tuberculosis and extensively drug-resistant tuberculosis
Time Frame: Up to Week 132
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Up to Week 132
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Time to sputum culture conversion
Time Frame: Up to Week 132
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Up to Week 132
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Number of patients with negative culture and smear for tuberculosis
Time Frame: Up to Week 132
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Up to Week 132
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Time to positive signal in Mycobacteria Growth Indicator Tube (MGIT960)
Time Frame: Up to Week 132
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Up to Week 132
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Number of patients with confirmed culture conversion by lung cavity status
Time Frame: Up to Week 132
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Up to Week 132
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Number of patients with confirmed culture conversion by geographic region
Time Frame: Up to Week 132
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Up to Week 132
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Number of patients with confirmed culture conversion by human immunodeficiency virus status
Time Frame: Up to Week 132
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Up to Week 132
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Number of patients with confirmed culture conversion by baseline resistance to anti-tuberculosis therapy
Time Frame: Up to Week 132
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Up to Week 132
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Number of patients with Tuberculosis Symptom Profile symptoms at Week 36 and at the end of the treatment-free follow up
Time Frame: Up to Week 132
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Up to Week 132
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Number of tuberculosis-related deaths per investigator assessment
Time Frame: Up to Week 132
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Up to Week 132
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Number of patients with weight gain (greater than 5 percent) at Week 36 and at the end of the treatment-free follow up
Time Frame: Up to Week 132
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Up to Week 132
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Number of patients with improvements in laboratory assessments at Week 36 and at the end of the treatment-free follow up
Time Frame: Up to Week 132
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Up to Week 132
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Number of patients with improvements in chest radiograph assessments at Week 36 and at the end of the treatment-free follow up
Time Frame: Up to Week 132
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Up to Week 132
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Number of patients that received salvage regimen with favorable treatment outcome 24 weeks after the end of the individualized salvage regimen
Time Frame: Up to Week 132
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Up to Week 132
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Mean plasma concentrations of TMC207
Time Frame: Up to Week 36
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Up to Week 36
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Mean plasma concentrations of N-monodesmethyl metabolite of TMC207
Time Frame: Up to Week 36
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Up to Week 36
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Number of patients affected by an adverse event
Time Frame: Up to Week 132
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Up to Week 132
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Number of patients with confirmed culture conversion at Week 36
Time Frame: Up to Week 132
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Up to Week 132
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Number of patients who required lung surgeries (resection or pneumonectomy) during the study
Time Frame: Week 84
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Week 84
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Number of patients with confirmed culture conversion by baseline albumin grade
Time Frame: Up to Week 132
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Up to Week 132
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Number of patients with confirmed culture conversion by baseline TMC207 minimal inhibitory concentration
Time Frame: Up to Week 132
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Minimal inhibitory concentration is defined as lowest concentration of an antimicrobial agent that will inhibit the visible growth of an organism.
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Up to Week 132
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Number of patients with confirmed culture conversion at Week 132
Time Frame: Week 132
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Week 132
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Number of patients who required lung surgeries (resection or pneumonectomy) during the study
Time Frame: Week 132
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Week 132
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Number of patients who experienced death
Time Frame: Up to Week 132
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Up to Week 132
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Number of patients will be qualified as cure based on the WHO outcome definition and the number of treatment failures, deaths, transfer out/defaults, and treatment completed
Time Frame: Up to Week 132
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Cure is defined as an multidrug-resistant tuberculosis (MDR-TB) patient who has completed the study procedures according to the protocol and has at least five consecutive negative cultures from samples collected at least 30 days apart in the final 12 months of the study.
If only one positive culture is reported during that time, a patient may still be considered cured, provided that this positive culture is followed by a minimum of 3 consecutive negative cultures taken at least 30 days apart.
Treatment failure is defined as a patient who completed the study procedures and was not cured as per the "Cure" definition based on the WHO classification during the study procedures.
Defaults is defined as patients who discontinued study procedures for any reason.
Treatment completed is defined as an MDR-TB patient who has completed the study procedures but does not meet the definition for cure or treatment failure due to lack of bacteriologic results.
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Up to Week 132
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2014
Primary Completion (Anticipated)
July 1, 2016
Study Completion (Anticipated)
November 1, 2022
Study Registration Dates
First Submitted
April 24, 2012
First Submitted That Met QC Criteria
May 16, 2012
First Posted (Estimate)
May 17, 2012
Study Record Updates
Last Update Posted (Estimate)
December 2, 2015
Last Update Submitted That Met QC Criteria
November 30, 2015
Last Verified
November 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CR100807
- TMC207-TIDP13-C210 (Other Identifier: Janssen Infectious Diseases BVBA)
- 2011-000653-23 (EudraCT Number)
- U1111-1135-7013 (Other Identifier: Universal Trial Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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