An Open-Label, Partially Randomized Trial to Evaluate the Efficacy, Safety and Tolerability of a 4-month Treatment of Bedaquiline Plus Pretomanid Plus Moxifloxacin Plus Pyrazinamide (BPaMZ) Compared to a 6-month Treatment of HRZE/HR (Control) in Adult Participants With Drug-Sensitive Smear-Positive Pulmonary Tuberculosis (DS-TB) and a 6-month Treatment of BPaMZ in Adult Participants With Drug Resistant, Smear-Positive Pulmonary Tuberculosis (DR-TB)

SimpliciTB (B-Pa-M-Z) NC-008

To evaluate the efficacy, safety and tolerability at 8 weeks (2-months), 52 weeks (12-months), and 104 Weeks (24-months) post the start of the following treatment regimens in participants with: Drug Sensitive TB (DS-TB) patients given BPaMZ for 17 Weeks ( or 4 months) vs. Standard HRZE/HR treatment given for 26 weeks (or 6 months) and Drug Resistant TB (DR-TB) patients given BPaMZ for 26 Weeks (or 6 months)

2018-07-30

2021-07-01

2022-06-10

Completed

Early phase I

455

Inclusion Criteria: * Sputum positive for tubercule bacilli (at least 1+ on the International Union Against Tuberculosis and Lung Disease \[IUATLD\]/WHO scale (Appendix 1) on smear microscopy) at the trial laboratory. * Participants with one of the following pulmonary TB conditions: DS-TB treatment arm participants should be: * sensitive to rifampicin and isoniazid by rapid sputum based test AND * either newly diagnosed for TB or have a history of being untreated for at least 3 years after cure from a previous episode of TB. DR-TB treatment arm participants should be Resistant to rifampicin and/or isoniazid. * Of non-childbearing potential or willing to practice effective methods of birth control * Body weight (in light clothing and no shoes) ≥ 30 kg. * Completed informed consent form Exclusion Criteria: * Karnofsky score \<60% * Any risk factor for QT prolongation * Any planned contraindicated medicines * Resistant to fluoroquinolones (rapid, sputum-based molecular screening tests). Any of the following lab toxicities/abnormalities: * CD4+ count \< 100 cells/µL (HIV infected participants) * platelets \<75,000/mm³ * creatinine \>1.5 times upper limit of normal (ULN) * eGFR ≤ 60 mL/min * haemoglobin \<8.0 g/dL * serum potassium less than the lower limit of normal for the laboratory. * GGT: greater than 3 x ULN * AST: ≥3.0 x ULN to be excluded; * ALT: ≥3.0 x ULN to be excluded * ALP: ≥3.0 x ULN to be excluded * Total bilirubin: \>1.5 x ULN to be excluded; * Direct bilirubin: greater than 1x ULN to be excluded

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2', 'PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Phase 2c multi-center, open-label, partially randomized clinical trial in DS-TB and DR-TB participants', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 455, 'type': 'ACTUAL'}}

2024-03-07