E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multi-drug resistant tuberculosis |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10044755 |
E.1.2 | Term | Tuberculosis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to demonstrate that TMC207 added to a BR is superior to this BR plus placebo in regard to the proportion of subjects with favourable treatment outcome 60 weeks after randomization (i.e., 36 weeks of treatment and 24 weeks of treatment-free follow-up).
A favourable treatment outcome requires confirmed culture conversion at Week 60. |
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E.2.2 | Secondary objectives of the trial |
For the secondary objectives please refer to chapter 2.1.2 of the Clinical Trial Protocol |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal exclusion criteria |
- Has TB infection that has been demonstrated prior to randomization to be extensively drug resistant
- 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of patients with favorable treatment outcome at Week 60 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1- Number of patients with confirmed culture conversion at Week 84
2- Number of patients with confirmed culture conversion at Week 60 or at time of trial discontinuation
3- The number of patients with development of pre-extensively drug-resistant
tuberculosis and extensively drug-resistant tuberculosis
4- Time to sputum culture conversion
5- Number of patients with negative culture and smear for tuberculosis
6- Time to positive signal in Mycobacteria Growth Indicator Tube (MGIT960)
7- Number of patients with confirmed culture conversion by lung cavity status
8- Number of patients with confirmed culture conversion by geographic region
9- Number of patients with confirmed culture conversion by human immunodeficiency virus status
10- Number of patients with confirmed culture conversion by baseline resistance to antituberculosis therapy
11- Number of patients with Tuberculosis Symptom Profile symptoms at Week 36 and at the end of the treatment-free follow up
12- Number of tuberculosis-related deaths per investigator assessment
13- Number of patients with weight gain at Week 36 and at the end of the treatment-free follow up
14- Number of patients with improvements in laboratory assessments at Week 36 and at the end of the treatment-free follow up
15- Number of patients with improvements in chest radiograph assessments at Week 36 and at the end of the treatment-free follow up
16 - Number of patients that received salvage regimen with favorable treatment outcome 24 weeks after the end of the individualized salvage regimen
17 - Mean plasma concentrations of TMC207
18- Mean plasma concentrations of N-monodesmethyl metabolite of TMC207
19- Number of patients affected by an adverse event |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- Week 84
2- Up to week 84
3- Up to week 84
4- Up to week 84
5- Up to week 84
6- Up to week 84
7- Up to week 84
8- Up to week 84
9- Up to week 84
10- Up to week 84
11- Up to week 84
12- Up to week 84
13- Up to week 84
14- Up to week 84
15- Up to week 84
16- Up to week 84
17- Up to week 36
18- Up to week 36
19- Up to week 84 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Cambodia |
China |
Colombia |
Estonia |
Korea, Democratic People's Republic of |
Latvia |
Peru |
Philippines |
Russian Federation |
South Africa |
Taiwan |
Thailand |
Turkey |
Ukraine |
Vietnam |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |