B14-10 Randomized Phase 2/3 Trial of an All-Oral Bedaquiline-Based Regimen for Refractory Mycobacterium Avium Complex (MAC) Lung Disease

Background

There are limited treatment options for refractory Mycobacterium avium complex (MAC) lung disease, which is defined as positive MAC cultures despite at least 6 months of guideline-based therapy. While bedaquiline, a diarylquinoline antibiotic, has been approved for multidrug-resistant pulmonary tuberculosis as part of combination therapy, but also has in vivo activity against MAC in murine models. The TMC207NTM3002 clinical trial evaluated an all-oral bedaquiline-based regimen for treatment of refractory MAC lung disease (NCT04630145). Here, we present the primary analysis results at Week 24.

Methods

This multicenter, randomized, open-label, active-controlled phase 2/3 clinical trial evaluated the efficacy and safety of an oral bedaquiline-based regimen, in which bedaquiline was co-administered with clarithromycin and ethambutol for 48 weeks (bedaquiline regimen), compared with a rifamycin-based regimen comprised of either rifampicin or rifabutin co-administered with clarithromycin and ethambutol for 60 weeks (control). Individuals with macrolide resistance at screening or cavities ≥2 cm in diameter on chest CT scan were excluded from participation. Participants from sites in Japan, South Korea and Taiwan were enrolled and randomized 1:1 to the bedaquiline regimen or control. The primary endpoint was the percentage of participants with sputum culture conversion, defined as three consecutive negative sputum cultures taken at least 25 days apart, at Week 24.

Results

Between January 2021 and March 2024, 129 adult participants were enrolled and randomized to the bedaquiline regimen (n = 65) or control (n = 64). The percentage of participants with sputum culture conversion at Week 24 was significantly higher in the bedaquiline regimen (24.6%,16/65) relative to control (4.7%, 3/64) (19.7% difference in proportion [95% CI 8.3% to 31.2%]; p = 0.002 by Cochran-Mantel-Haenszel test stratified by region). Serious adverse events were reported in 6.2% (4/65) participants in the bedaquiline regimen and 3.1% (2/64) participants in control up to Week 24. No serious adverse events were related to bedaquiline, and no safety concerns with bedaquiline were identified.

Conclusions

In the phase 2/3 randomized controlled trial of participants with refractory MAC lung disease, the oral bedaquiline-based regimen demonstrated superior efficacy relative to a control regimen in achievement of sputum culture conversion at Week 24. Bedaquiline was safe and well tolerated with a low rate of treatment-limiting adverse events.

This abstract is funded by: Johnson & Johnson