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

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Brazil
      • Porto Alegre, Brazil
      • Rio De Janeiro, Brazil
      • Sao Paulo, Brazil
  • Cambodia
      • Phnom Penh, Cambodia
  • China
      • Beijing, China
      • Changsha, China
      • Chongqing, China
      • Fuzhou, China
      • Jinan, China
      • Nanjing, China
      • Shanghai, China
  • Estonia
      • Kohtla-Järve, Estonia
      • Talinn, Estonia
  • Ethiopia
      • Addis Ababa, Ethiopia
      • Gondar, Ethiopia
  • Georgia
      • Tbilisi, Georgia
  • Korea, Republic of
      • Busan, Korea, Republic of
      • Daegu, Korea, Republic of
      • Gwangju, Korea, Republic of
      • Gyeongsangnam-Do, Korea, Republic of
      • Incheon, Korea, Republic of
      • Seoul, Korea, Republic of
  • Latvia
      • Stopinu Region, Latvia
  • Mexico
      • Monterrey, Mexico
  • Peru
      • Lima, Peru
  • Philippines
      • Quezon City, Philippines
  • Russian Federation
      • Arkhangelsk, Russian Federation
      • Ekaterinburg, Russian Federation
      • Moscow, Russian Federation
      • Novosibirsk, Russian Federation
      • Orel, Russian Federation
      • Saint-Petersburg, Russian Federation
  • South Africa
      • Paarl, South Africa
      • Sandringham, South Africa
      • Ysterplaat, South Africa
  • Taiwan
      • Changhua County, Taiwan
      • New Taipei City, Taiwan
      • Taichung, Taiwan
      • Tainan, Taiwan
  • Thailand
      • Nonthaburi, Thailand
  • Turkey
      • Kecioren, Turkey
  • Ukraine
      • Donetsk, Ukraine
      • Kiev, Ukraine
      • Ternopil, Ukraine

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm A
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: 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.
Placebo Comparator: Arm B
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.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Number of patients with favorable treatment outcome at Week 60
Time Frame: Week 60
Week 60

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of patients with confirmed culture conversion at Week 84
Time Frame: Week 84
Week 84
Number of patients with confirmed culture conversion at Week 60 or at time of trial discontinuation
Time Frame: Up to Week 132
Up to Week 132
The number of patients with development of pre-extensively drug-resistant tuberculosis and extensively drug-resistant tuberculosis
Time Frame: Up to Week 132
Up to Week 132
Time to sputum culture conversion
Time Frame: Up to Week 132
Up to Week 132
Number of patients with negative culture and smear for tuberculosis
Time Frame: Up to Week 132
Up to Week 132
Time to positive signal in Mycobacteria Growth Indicator Tube (MGIT960)
Time Frame: Up to Week 132
Up to Week 132
Number of patients with confirmed culture conversion by lung cavity status
Time Frame: Up to Week 132
Up to Week 132
Number of patients with confirmed culture conversion by geographic region
Time Frame: Up to Week 132
Up to Week 132
Number of patients with confirmed culture conversion by human immunodeficiency virus status
Time Frame: Up to Week 132
Up to Week 132
Number of patients with confirmed culture conversion by baseline resistance to anti-tuberculosis therapy
Time Frame: Up to Week 132
Up to Week 132
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
Up to Week 132
Number of tuberculosis-related deaths per investigator assessment
Time Frame: Up to Week 132
Up to Week 132
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
Up to Week 132
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
Up to Week 132
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
Up to Week 132
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
Up to Week 132
Mean plasma concentrations of TMC207
Time Frame: Up to Week 36
Up to Week 36
Mean plasma concentrations of N-monodesmethyl metabolite of TMC207
Time Frame: Up to Week 36
Up to Week 36
Number of patients affected by an adverse event
Time Frame: Up to Week 132
Up to Week 132
Number of patients with confirmed culture conversion at Week 36
Time Frame: Up to Week 132
Up to Week 132
Number of patients who required lung surgeries (resection or pneumonectomy) during the study
Time Frame: Week 84
Week 84
Number of patients with confirmed culture conversion by baseline albumin grade
Time Frame: Up to Week 132
Up to Week 132
Number of patients with confirmed culture conversion by baseline TMC207 minimal inhibitory concentration
Time Frame: Up to Week 132
Minimal inhibitory concentration is defined as lowest concentration of an antimicrobial agent that will inhibit the visible growth of an organism.
Up to Week 132
Number of patients with confirmed culture conversion at Week 132
Time Frame: Week 132
Week 132
Number of patients who required lung surgeries (resection or pneumonectomy) during the study
Time Frame: Week 132
Week 132
Number of patients who experienced death
Time Frame: Up to Week 132
Up to Week 132
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
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.
Up to Week 132

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Infectious Diseases BVBA

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2014

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2016

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 24, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 16, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 17, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 2, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 30, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings