Phase 2C clinical trial of novel, short-course regimens for the treatment of pulmonary tuberculosis: CRUSH-TB (Combination Regimens for Shortening TB Treatment; TBTC Study 38)
Information:
Sponsor – U.S. Centers for Disease Control & Prevention (75D30121C10164)
Principal Investigator – John L. Johnson, MD, ÐÇ¿Õ´«Ã½
| Type of Study | Phase 2C Clinical Trial |
|---|---|
| Design | Multi-Center, open-label, randomized, 3-arm clinical trial with adaptive design allowing for introduction of novel regimens once they are clinically ready for testing |
| Project Site | Kampala, Uganda |
| Sample Size | A total of at least 288 male and female participants (96/arm) at all study sites with newly diagnosed with sputum smear positive or GeneXpert positive pulmonary tuberculosis, aged 12 years or older, with normal QTcF on screening ECG |
| Study Period | Individual participant duration of follow-up is 12-18 months |
Goal of Study:
Assess the efficacy and safety of several regimens based on novel agents in the treatment of drug-sensitive TB disease; assessing mycobactericidal activity of 17-week treatments of bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z)-- (BMZ)-- plus rifabutin (Rb) (2 BMZRb/2 BMRb, Arm 1) or BMZ plus delamanid (D or DLM) (2 BMZD/2 BMD, Arm 2) compared to 26-week standard treatment with first-line TB drugs (isoniazid, rifampin, pyrazinamide, ethambutol, HRZE, Arm 3).
Primary Objective:
Time to sputum culture negative in liquid media
Secondary Objectives:
- Proportion of participants with a Grade 3 or higher adverse event during 26 weeks from randomization
- Lack of sustained cure during treatment or follow-up to 52 weeks
- Time to sputum culture negative in solid media
- Proportion of participants with sputum culture negative by 8 weeks and by 12 weeks (solid and liquid media).
- All-cause study drug discontinuation
- The rate of change in time to sputum culture positivity (TTP) through 17 weeks in the Mycobacterial Growth Indicator Tube (Bactec MGIT960)
- Lack of sustained cure during treatment or follow-up to 78 weeks
- Population pharmacokinetics (PK) of bedaquiline, with or without rifabutin
- Pharmacokinetic/pharmacodynamic (PK/PD) relationship between test drug PK parameters and microbiologic outcomes