NCT02754765

Evaluating Newly Approved Drugs for Multidrug-resistant TB

Evaluating Newly Approved Drugs for Multidrug-resistant TB (endTB): A Clinical Trial

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 754 (actual)
• Sponsor: Médecins Sans Frontières, France · Academic / Other
• Sex: All
• Age: 15 Years
• Healthy volunteers: Not accepted

Summary

endTB Clinical Trial a Phase III, randomized, controlled, open-label, non-inferiority, multi-country trial evaluating the efficacy and safety of five new, all-oral, shortened regimens for multidrug-resistant tuberculosis (MDR-TB).

Detailed description

This is a Phase III, randomized, controlled, open-label, non-inferiority, multi-country trial evaluating the efficacy and safety of new combination regimens for MDR-TB treatment. Regimens examined combine newly approved drugs bedaquiline and/or delamanid with existing drugs known to be active against Mycobacterium tuberculosis (linezolid, clofazimine, moxifloxacin or levofloxacin, and pyrazinamide). The study will enroll in parallel across 5 experimental and 1 standard-of-care control arms. Randomization will be outcome adapted using Bayesian interim analysis of efficacy endpoints. Experimental regimens will contain bedaquiline and/or delamanid and up to 4 companion drugs. Control-arm treatment may contain one of the following (bedaquiline or delamanid) and companion drugs, constructed and delivered according to local standard of care and consistent with WHO guidelines. Trial participation in all arms will last at least until Week 73, and up to Week 104. In the experimental arms, treatment will be for 39 weeks (participants in the experimental arms will be allowed up to 47 weeks to complete the 39-week treatment course) and post-treatment follow up for up to 65 additional weeks. In the control arm, treatment will be delivered according to local standard of care (in consistence with WHO guidance); duration may vary and will be approximately 86 weeks for the conventional regimen and 39-52 weeks for the standardized shorter regimen. Non-inferiority will be established for any experimental arm if the lower bound of the one-sided 97.5% confidence interval around the difference in favorable outcome between the control and experimental arms is greater than or equal to -12%.

Conditions

• Tuberculosis, Multidrug-Resistant
• Infection, Bacterial
• Pulmonary Tuberculoses

Interventions

Type	Name	Description
DRUG	Bedaquiline
DRUG	Delamanid
DRUG	Clofazimine
DRUG	Levofloxacin
DRUG	Moxifloxacin
DRUG	Linezolid
DRUG	Pyrazinamide
DRUG	Control arm MDR-TB regimen, consistent with WHO guidelines	Control arm MDR-TB regimen, consistent WHO guidelines

Timeline

• Start date: 2016-12-01
• Primary completion: 2023-06-01
• Completion: 2023-06-01
• First posted: 2016-04-28
• Last updated: 2025-02-10

Locations

12 sites across 7 countries: Georgia, India, Kazakhstan, Lesotho, Pakistan, Peru, South Africa