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An Exploratory Study of TMC207 in Japanese Participants With Pulmonary Multi-Drug Resistant Tuberculosis (MDR-TB)

Primary Purpose

Tuberculosis, Multidrug-Resistant

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
TMC207 (bedaquiline)
Background Regimen (BR)
Sponsored by
Janssen Pharmaceutical K.K.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberculosis, Multidrug-Resistant focused on measuring Pulmonary Multi-Drug Resistant Tuberculosis (MDR-TB), TMC207, Bedaquiline

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Must have confirmed pulmonary multi-drug resistant tuberculosis (MDR-TB) infection, which is defined as infection by a strain of M. tuberculosis resistant to both rifampicin and isoniazid (RFP and INH) by previous screening from a TB treatment
  • Must have confirmed positive results for acid-fast bacilli (AFB) on direct smear examination of expectorated sputum specimen (more than [>] 1+ smear-positive) during the Screening Phase or sputum culture positive for M. tuberculosis within the preceding 3 months
  • A women must not be of childbearing potential: postmenopausal or permanently sterilized or otherwise be incapable of pregnancy, or if childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods and a man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control
  • Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
  • Must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

  • Has any concomitant severe illness or rapidly deteriorating health condition, including immune deficiency that would make implementation of the protocol or interpretation of the study results difficult or otherwise make the subject a poor candidate for a clinical study
  • Has complicated or severe extra-pulmonary manifestations of TB, including central nervous system infection
  • Participants with significant cardiac arrhythmia requiring medication
  • Participants with the abnormal electrocardiogram (ECG) parameters as defined in protocol
  • Has human immuno deficiency virus (HIV) antibody positive during the Screening Phase

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TMC207 (bedaquiline) + Background Regimen (BR)

Arm Description

Participants will receive TMC207 (bedaquiline) 400 milligram (mg) as 4*100 mg tablets once daily 2 weeks (14 days). From Week 3, participants will receive 200 mg (2 tablets) TMC207 (bedaquiline) 3 times a week up to Week 24 along with background regimen (BR). Based on the discussion with the Pharmaceuticals and Medical Devices Agency (PMDA), the extension of 24-week TMC207 treatment with BR drugs may occur up to Week 48, under certain circumstances, such that many BR drugs which are susceptible at the beginning of the Treatment Phase show resistance during the Treatment Phase. After TMC207 is stopped, the BR will be continued up to 78 weeks after conversion or 102 weeks after day 1 (what happens first).

Outcomes

Primary Outcome Measures

Percentage of Participants With Sputum Culture Conversion
Sputum culture conversion is defined as 2 consecutive negative cultures from sputa collected at least 25 days apart.

Secondary Outcome Measures

Number of Participants With Multidrug resistant (MDRTB) Outcome
Outcome is defined as, Cured: Participants who completed the study and has been consistently culture-negative (at least 5 consecutive negative cultures) for at least 48 weeks. If only 1 positive culture is reported in that time, participant may still be considered cured, provided that this positive culture is followed by a minimum of 3 consecutive negative cultures. Treatment failure: Participants who completed the study and was not cured. Death: Participants who died during study. Participants reported as dead during survival follow-up before or within Week 126 window were included in this category. Participants reported as dead during after Week 126 window are not included in this category as event occurred after planned duration (126 weeks) of study. Transfer out/Default: Participants who discontinued from study for any reason. Treatment completed: Participants who completed the study but did not meet definition for cure or treatment failure due to lack of bacteriologic results.

Full Information

First Posted
February 13, 2015
Last Updated
October 30, 2019
Sponsor
Janssen Pharmaceutical K.K.
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1. Study Identification

Unique Protocol Identification Number
NCT02365623
Brief Title
An Exploratory Study of TMC207 in Japanese Participants With Pulmonary Multi-Drug Resistant Tuberculosis (MDR-TB)
Official Title
An Open-Label Study to Explore the Safety, Efficacy and Pharmacokinetics of TMC207 in Japanese Patients With Pulmonary Multi-Drug Resistant Tuberculosis (MDR-TB)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
February 18, 2015 (Actual)
Primary Completion Date
November 8, 2018 (Actual)
Study Completion Date
November 8, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Pharmaceutical K.K.

4. Oversight

Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to explore safety and efficacy of TMC207 administered as part of a multi-drug regimen for 24 to 48-week treatment in Japanese participants with pulmonary multi-drug resistant tuberculosis (MDR-TB), and to evaluate pharmacokinetics (PK) of TMC207 and its primary metabolite M2.
Detailed Description
This is an open-label (everyone know the study intervention), single-arm, multicenter trial to explore safety, efficacy and PK of TMC207 in Japanese participants with pulmonary MDR-TB. The participants will receive TMC207 for 24 weeks in combination with individualized BR drugs selected by the Investigator on Day -1. Participants will primarily be assessed for sputum culture conversion at Week 24. Safety will be monitored throughout the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, Multidrug-Resistant
Keywords
Pulmonary Multi-Drug Resistant Tuberculosis (MDR-TB), TMC207, Bedaquiline

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TMC207 (bedaquiline) + Background Regimen (BR)
Arm Type
Experimental
Arm Description
Participants will receive TMC207 (bedaquiline) 400 milligram (mg) as 4*100 mg tablets once daily 2 weeks (14 days). From Week 3, participants will receive 200 mg (2 tablets) TMC207 (bedaquiline) 3 times a week up to Week 24 along with background regimen (BR). Based on the discussion with the Pharmaceuticals and Medical Devices Agency (PMDA), the extension of 24-week TMC207 treatment with BR drugs may occur up to Week 48, under certain circumstances, such that many BR drugs which are susceptible at the beginning of the Treatment Phase show resistance during the Treatment Phase. After TMC207 is stopped, the BR will be continued up to 78 weeks after conversion or 102 weeks after day 1 (what happens first).
Intervention Type
Drug
Intervention Name(s)
TMC207 (bedaquiline)
Other Intervention Name(s)
Bedaquiline
Intervention Description
TMC207 (bedaquiline): Participants will receive TMC207 (bedaquiline) 400 milligram (mg) as 4*100 mg tablets once daily 2 weeks (14 days) followed by 200 mg (2 tablets) 3 times a week up to Week 24 along with background regimen (BR). Based on the discussion with the Pharmaceuticals and Medical Devices Agency (PMDA), the extension of 24-week TMC207 treatment with BR drugs may occur up to Week 48, under certain circumstances, such that many BR drugs which are susceptible at the beginning of the Treatment Phase show resistance during the Treatment Phase.
Intervention Type
Drug
Intervention Name(s)
Background Regimen (BR)
Intervention Description
Participants will receive anti-bacterial tuberculosis drugs (pyrazinamide [PZA], ethambutol [EB, EMB], streptomycin [SM], kanamycin [KM, KAN], enviomycin [EVM], ethionamide [TH], cycloserine [CS], para-aminosalicylic acid [PAS], amikacin [AMK], levofloxacin [LVFX] and other fluoroquinolone. Other drugs are used less commonly, such as amoxicillin-clavulanate, linezolid and clofazimine based on Investigator's decision twice a week from Day 1 up to 78 weeks after conversion or 102 weeks after day 1 (what happens first).
Primary Outcome Measure Information:
Title
Percentage of Participants With Sputum Culture Conversion
Description
Sputum culture conversion is defined as 2 consecutive negative cultures from sputa collected at least 25 days apart.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Number of Participants With Multidrug resistant (MDRTB) Outcome
Description
Outcome is defined as, Cured: Participants who completed the study and has been consistently culture-negative (at least 5 consecutive negative cultures) for at least 48 weeks. If only 1 positive culture is reported in that time, participant may still be considered cured, provided that this positive culture is followed by a minimum of 3 consecutive negative cultures. Treatment failure: Participants who completed the study and was not cured. Death: Participants who died during study. Participants reported as dead during survival follow-up before or within Week 126 window were included in this category. Participants reported as dead during after Week 126 window are not included in this category as event occurred after planned duration (126 weeks) of study. Transfer out/Default: Participants who discontinued from study for any reason. Treatment completed: Participants who completed the study but did not meet definition for cure or treatment failure due to lack of bacteriologic results.
Time Frame
Week 102

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Must have confirmed pulmonary multi-drug resistant tuberculosis (MDR-TB) infection, which is defined as infection by a strain of M. tuberculosis resistant to both rifampicin and isoniazid (RFP and INH) by previous screening from a TB treatment Must have confirmed positive results for acid-fast bacilli (AFB) on direct smear examination of expectorated sputum specimen (more than [>] 1+ smear-positive) during the Screening Phase or sputum culture positive for M. tuberculosis within the preceding 3 months A women must not be of childbearing potential: postmenopausal or permanently sterilized or otherwise be incapable of pregnancy, or if childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods and a man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol Must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study Exclusion Criteria: Has any concomitant severe illness or rapidly deteriorating health condition, including immune deficiency that would make implementation of the protocol or interpretation of the study results difficult or otherwise make the subject a poor candidate for a clinical study Has complicated or severe extra-pulmonary manifestations of TB, including central nervous system infection Participants with significant cardiac arrhythmia requiring medication Participants with the abnormal electrocardiogram (ECG) parameters as defined in protocol Has human immuno deficiency virus (HIV) antibody positive during the Screening Phase
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Pharmaceutical K.K. Clinical Trial
Organizational Affiliation
Janssen Pharmaceutical K.K.
Official's Role
Study Director
Facility Information:
City
Kiyose
Country
Japan
City
Sakai
Country
Japan

12. IPD Sharing Statement

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An Exploratory Study of TMC207 in Japanese Participants With Pulmonary Multi-Drug Resistant Tuberculosis (MDR-TB)

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