Trial to Evaluate the Efficacy, Safety and Tolerability of BPaMZ in Drug-Sensitive (DS-TB) Adult Patients and Drug-Resistant (DR-TB) Adult Patients

Global Alliance for TB Drug Development

Status and phase: Completed; Phase 3; Phase 2

Conditions: Drug-Resistant Tuberculosis; Tuberculosis; Tuberculosis, MDR; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Treatments: Drug: Moxifloxacin; Drug: HR; Drug: Bedaquiline; Drug: Pyrazinamide; Drug: HRZE; Drug: Pretomanid

Study type: Interventional

Funder types: Other

Identifiers

NCT03338621

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

Details and patient eligibility

About

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)

Full description

Phase 2c multi-center, open-label, partially randomized clinical trial in DS-TB and DR-TB participants.

All participants in the below arms will have follow-up for a period of 104 weeks (24 months) from the start of therapy.

Participants with Drug Sensitive TB (DS-TB):

Participants with DS-TB will be randomized to one of two treatment arms. These participants will receive either BPaMZ daily for 17 weeks (4 months), or HRZE/HR combination tablets daily for 26 weeks (6 months). participants will be stratified for co-infection with human immunodeficiency virus (HIV) and cavitation.

Participants with Drug Resistant TB (DR-TB):

Participants with DR-TB will be assigned to receive BPaMZ daily for 26 weeks (6 months).

Enrollment: 455 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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455 participants in 3 patient groups

Drug Sensitive BPaMZ

Experimental group

Description:

Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 9 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 17 weeks (Total treatment duration 4 months

Treatment:

Drug: Pretomanid

Drug: Pyrazinamide

Drug: Bedaquiline

Drug: Moxifloxacin

Drug Sensitive Standard Treatment

Active Comparator group

Description:

isoniazid 75 mg + rifampicin 150 mg + pyrazinamide 400 mg + ethambutol 275 mg (HRZE) combination tablets for 8 weeks AND isoniazid 75 mg + rifampicin 150 mg (HR) combination tablets for Weeks 9 to 26

Treatment:

Drug: HRZE

Drug: HR

Drug Resistant BPaMZ

Experimental group

Description:

Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 18 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 26 weeks (Total treatment duration 6 months)

Treatment:

Drug: Pretomanid

Drug: Pyrazinamide

Drug: Bedaquiline

Drug: Moxifloxacin