TMC207TBC3001 - Early Access of TMC207 in Patients with Extensively Drug Resistant (XDR) or Pre-XDR Pulmonary Tuberculosis (TB)

Phase 1

• Conditions: Tuberculosis (TB); MedDRA version: 14.1Level: PTClassification code 10044755Term: TuberculosisSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2010-021125-12-LT
• Lead Sponsor: Janssen Infectious Diseases BVBA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-06-01
• Last Update Posted: 9 January 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 295

Inclusion Criteria

1. Male or female subject with confirmed pulmonary XDR or pre-XDR-TB infection with resistance to INH, RMP, and to a FQ and/or injectable 2nd line TB drug (kanamycin, amikacin, or capreomycin). Confirmation should include previous (within the preceding 6 months) smear or culture and DST results demonstrating pulmonary TB with an XDR or pre-XDR resistance pattern.
2. Subject has limited or no treatment options and is unable/ineligible to participate in any other TMC207 study.
3. Aged = 18 years.
4. Subject will be managed at a medical center that has been certified by the Green Light Committee of the WHO Stop TB Partnership, OR, following an assessment of the site confirms that the site meets equivalent standards, including DOTS-Plus-equivalent supervision of medication administration; laboratory capacity to provide regular sputum cultures and drug susceptibility tests (DST); and an uninterrupted supply of approved second line drugs with which to create a companion BR.
5. Medically stable in the opinion of the investigator on the basis of physical examination, and safety examinations performed at screening.
6. All women of childbearing potential must have a negative urine pregnancy test at screening.
7. Women must:
– be postmenopausal for at least 2 years, or
– be surgically sterile (have had a total hysterectomy or bilateral oophorectomy, tubal ligation/bilateral tubal clips without reversal operation, or otherwise be incapable of
pregnancy), or
– not be heterosexually active for the duration of the early access study, or
– be practicing a highly effective method of birth control (as specified below), and agree to continue to use the same method of contraception throughout TB treatment:
? Use a double barrier method (i.e., male condom + either diaphragm or cervical cap),
or
? Use non-estrogen hormonal based contraceptives in combination with a barrier
contraceptive (i.e., male condom, diaphragm or cervical cap, or femal condom), or
? Use an intrauterine device in combination with a barrier contraceptive (i.e., male condom, diaphragm or cervical cap, or female condom).
Note: A male and female condom should not be used together due to risk of breakage or damage caused by latex friction.
8. Men must agree to use a highly effective method of birth control (i.e., male condom with either female intrauterine device, diaphragm, cervical cap or [non-estrogen] hormonal based contraceptives) and not to donate sperm during the early access study and for 3 months after receiving the last dose of TB treatment.
Note: A male and female condom should not be used together due to risk of breakage or damage caused by latex friction.
9. Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the early access study.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 290
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

1. History of and/or clinically relevant, currently active or underlying gastrointestinal, cardiovascular, nervous system, psychiatric, metabolic, renal, respiratory (other than due to TB), inflammatory, neoplastic, skin, immunological or infectious disease, which is not stable and controlled.
If there are clinically relevant, currently active or underlying diseases, they should not compromise the safety of the subject or the ability to participate in the study as judged by the investigator. The investigator is encouraged to discuss concomitant illnesses with the sponsor.
2. Subjects with complicated or severe extra pulmonary manifestations of TB, including osteoarticular and central nervous system infection.
3. HIV-infected subjects who cannot be treated with antiretroviral (ARVs) regimens as outlined in Section 4.4 during administration of TMC207.
4. Having received TMC207 in a previous study.
5. Subject is eligible for other Tibotec sponsored TMC207 studies.
6. Known allergies, hypersensitivity, or intolerance to TMC207 or its excipients.
7. Use of disallowed therapies as specified in the section of disallowed medication (see Section 8). 8. Are currently enrolled in another investigational study or have been enrolled in an
investigational study within 60 days before the planned start of treatment with TMC207, unless approved by the sponsor.
9. Pregnant or breast-feeding.
10. Any condition that, in the opinion of the investigator, would compromise the early access study or the well-being of the subject or prevent the subject from meeting or performing protocol requirements.
11. Current alcohol, barbiturate, amphetamine, recreational or narcotic drug use, which in the investigator’s opinion would compromise subject’s safety and/or compliance with the protocol procedures.
12. Subjects with the following laboratory abnormalities at screening as defined by the DMID Adult Toxicity Table and in accordance with the normal ranges of the clinical laboratory at the site:
- serum creatinine grade 1 or greater (> 1.0 x ULN);
- lipase grade 2 (with no signs or symptoms of pancreatitis) or greater (> 1.5 x ULN);
- AST or ALT grade 2 or greater (= 2.0 - < 3.0 x ULN);
- total bilirubin grade 1 or greater (> 1.0 x ULN).
Note: If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges (including the above listed parameters), the subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically relevant or to be appropriate and reasonable for the population under study. This determination must be recorded in the subject's source documents and initialed by the investigator.
13. Subjects with QTcF interval > 450 msec at screening (and, if above the limit, confirmed by repeat single ECG).
14. Subjects with any other clinically significant ECG abnormality at screening, such as arrhythmia, ischemia, or evidence of heart failure.
15. Subjects with a family history of Long QT Syndrome.
16. Vulnerable subjects (e.g., persons kept in detention).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to provide early access to TMC207 for subjects who have pulmonary infection due to strains of M. tuberculosis with resistance to INH, RMP, and to a fluoroquinolone (FQ) and/or injectable 2nd line TB drug(kanamycin, amikacin, or capreomycin).;Secondary Objective: The secondary objective is to evaluate the safety and tolerability of TMC207. In addition, the results of microbiology assessments which are recommended to be performed during the early access study will be described.;Primary end point(s): This early access study will be conducted to make TMC207 available to subjects with extensively drug resistant (XDR) or pre-XDR TB infection who have limited-to-no treatment options. Data collection will be limited and no statistical hypotheses will be tested.;Timepoint(s) of evaluation of this end point: Not applicable

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable