Building Evidence for Advancing New Treatment for Rifampicin Resistant Tuberculosis (RR-TB) Comparing a Short Course of Treatment (Containing Bedaquiline, Delamanid and Linezolid) With the Current South African Standard of Care

• Status: Recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

Summary

BEAT Tuberculosis is a phase 3, open label, multi-centre, randomized controlled trial. The purpose of this trial is to compare the efficacy and safety of a Study Strategy consisting of 6 months of bedaquiline (BDQ), delamanid (DLM), and linezolid (LNZ), with levofloxacin (LVX) and clofazimine (CFZ) compared to the current South African Standard of Care (Control Strategy) for 9 months for the treatment of rifampicin resistant (RR-TB) Tuberculosis.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Wits Health Consortium (Pty) Ltd
• Collaborators: Perinatal HIV Research Unit of the University of the Witswatersrand; Regents of the University of California; University of Cape Town
• Treatments: Bedaquiline; Clofazimine; Diarylquinolines; Ethambutol; Fluoroquinolones; Isoniazid; Levofloxacin; Linezolid; Ofloxacin; Pyrazinamide; Rifampin

Criteria

Inclusion Criteria:

• Willing and able to give informed consent to be enrolled in the research study prior to any study related procedures (signed or witnessed consent if the participant is unable to read and understand the informed consent document; signed or witnessed consent from a child's biological parent, legal guardian or primary caregiver) and if the participant is a child (12-17 years) is willing to sign assent

• Willing and able to adhere to the complete follow-up schedule and to study procedures

• Male or female, aged 12 years or older

• Weigh more than or equal to 30kg

• Have confirmed Pulmonary TB with initial laboratory result of resistance to at least rifampicin as confirmed by genotypic or phenotypic susceptibility testing in the last three months

• Willing to use effective contraception for females of child bearing potential if sexually active; must be willing to use either an intrauterine contraceptive device or a hormonal method for the duration of the treatment regimen and for three months thereafter

• Willing to have an HIV test and if positive is willing to be treated with appropriate antiretroviral therapy

Exclusion Criteria:

• Had taken more than 28 days but less than 24 weeks of second line TB drugs including BDQ, LNZ, CFZ, fluoroquinolones or DLM.

Please note: Participants with prior successfully treated episodes of DR TB are permitted to enroll.

• Is pregnant or breastfeeding

• Has complicated or severe extra-pulmonary manifestations of TB, including osteo-articular, pericardial and central nervous system infection as per investigators opinion

• Is unable to take oral medication

• Is taking any prohibited medications as referred to in the protocol

• Has a known allergy or hypersensitivity to any of the medicines in the regimens

• Is currently taking part in another clinical trial of any medicinal product

• Has a QTcF interval of greater than 450 ms. Please note: If the QTcF interval is greater than 450 ms, it may be repeated if participant has reversible contributory factors, i.e. low potassium or to allow washout of previous QT prolonging drugs.

• Has clinically significant ECG abnormality in the opinion of the site investigator within 60 days prior to entry, including but not limited to second or third degree atrioventricular (AV) block or clinically important arrhythmia

• Participants with the following laboratory abnormality at screening.

1. Hemoglobin level of < 8.0 g/dL

2. Platelet count < 75,000/mm^3

3. Absolute neutrophil count (ANC) < 1000/ mm^3

4. An estimated creatinine clearance (CrCl) less than 30 mL/min as calculated by the National Health Laboratory Service (NHLS) equation

5. Alanine aminotransferase (ALT) ≥3 x upper limit of normal (ULN)

6. Total bilirubin grade 3 or greater (>2.0 x ULN, or >1.50 x ULN when accompanied by any increase in other liver function test)

7. Serum potassium less than 3.2 mmol/l

• Peripheral neuropathy of grade 3 or 4 using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events

• If in the investigator's opinion, the participant is unable to commit to study related procedures or it is unsafe for the participant to take part in the study