A Study of an Oral Short-course Regimen Including Bedaquiline for the Treatment of Participants With Multidrug-resistant Tuberculosis in China (PROSPECT)

Beijing Chest Hospital

Status and phase: Enrolling; Phase 4

Conditions: Tuberculosis, Multidrug-Resistant

Treatments: Drug: Linezolid; Drug: Protionamide; Drug: Bedaquiline; Drug: Cycloserine; Drug: Levofloxacin; Drug: Pyrazinamide; Drug: Clofazimine

Study type: Interventional

Funder types: Other

Identifiers

NCT05306223

TMC207TBC4006 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate efficacy and safety of an oral bedaquiline-containing multidrug-resistant tuberculosis (MDR-TB) short-course regimen (SCR) compared to an oral SCR not including bedaquiline at the end of treatment in participants with pulmonary MDR-TB in China.

Enrollment: 212 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has a positive sputum Mycobacterium tuberculosis culture from a test performed at screening
• Has microbiological confirmation of rifampicin resistance by GeneXpert and to isoniazid (INH) via molecular drug-susceptibility testing (DST) showing katG mutation
• Has a chest imaging result compatible with a diagnosis of pulmonary Tuberculosis (TB)
• Agrees to use effective contraception during the 40-week study treatment phase. A female participant must be: of nonchildbearing potential; of childbearing potential and practicing effective methods of contraception during the 40-week study treatment phase
• Is willing to undergo human immunodeficiency virus (HIV) testing

Exclusion criteria

• Has received prior treatment with bedaquiline
• Has prior exposure to at least 1 second-line drug in the regimen for at least 4 weeks
• Has any grade 3 or 4 laboratory abnormality as confirmed by a clinical expert
• Has a known allergy or intolerance to bedaquiline or other drugs in the regimen
• Is infected with a strain of nontuberculous mycobacteria
• Is HIV-positive

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

212 participants in 2 patient groups

Bedaquiline-containing Short-course Regimen (SCR)

Experimental group

Description:

Participants will receive an oral dose of bedaquiline 400 milligrams (mg) once daily for first 2 weeks followed by bedaquiline 200 mg thrice a week for 22 weeks (with at least 48 hours between doses) in combination with oral doses of levofloxacin (LFX) up to 1000 mg (weight-based), cycloserine (CS) up to 750 mg (weight-based), clofazimine (CFZ) 100 mg daily for 40 weeks and linezolid \[LZD\] 600 mg daily for at least 24 weeks . If a participant is still sputum culture-positive for Mycobacterium tuberculosis by Week 16, bedaquiline treatment will be extended from Week 24 to Week 40.

Treatment:

Drug: Linezolid

Drug: Levofloxacin

Drug: Bedaquiline

Drug: Clofazimine

Drug: Cycloserine

Non-bedaquiline-containing Short-course Regimen (SCR)

Experimental group

Description:

Participants will receive oral doses of LFX up to 1000 mg (weight-based), CS up to 750 mg (weight-based), CFZ 100 mg, Pyrazinamide (PZA) up to 2000 mg (weight-based), Protionamide (PTO) up to 800 mg (weight-based) daily for first 16 weeks and LZD 600 mg daily for at least 24 weeks.

Treatment:

Drug: Linezolid

Drug: Protionamide

Drug: Levofloxacin

Drug: Pyrazinamide

Drug: Clofazimine

Drug: Cycloserine