“Finding the Optimal Regimen for Mycobacterium abscessus Treatment” (FORMaT) is a multi-site, international, investigator-led adaptive platform trial (APT) which aims to find the most effective and well tolerated treatment for MABC-PD. There is an intensive treatment phase using intravenous (IV) and oral antimicrobials (see Table 1) followed by a consolidation treatment phase each with separate randomisations. The APT has 3 nested trials – the first nested trial and the first interim analysis compares efficacy and tolerance of the 3 intensive therapy arms at 6 weeks.
Table 1: FORMaT Intensive Phase Treatment Arms
| Intensive Arm A (REFERENCE ARM) | Intensive Arm B | Intensive Arm C |
|---|---|---|
| 1. IV amikacin | 1. Inhaled amikacin | 1. IV amikacin |
| 2. IV tigecycline (>8yrs) | 2. IV tigecycline (>8yrs) | 2. IV tigecycline (>8yrs) |
| 3. IV imipenem or cefoxitin | 3. IV imipenem or cefoxitin | 3. IV imipenem or cefoxitin |
| 4. Oral azithromycin or clarithromycin | 4. Oral azithromycin or clarithromycin | 4. Oral azithromycin or clarithromycin |
| 5. Oral clofazimine | 5. Oral clofazimine |
The first interim analysis in May 2026 included data from 61 participants who completed 6 weeks intensive therapy. It compared the primary outcome between participants in the 2 test arms (Arms B and C) with the reference arm (Arm A). Across group data is presented, as between-group data will not be available until an intervention has completed its evaluation.
The primary outcome is MABC clearance with treatment tolerance. MABC clearance is defined as 3 negative respiratory samples (sputum/induced sputum) or 1 negative bronchoalveolar lavage collected at Week 4 and interpreted at Week 6. Only adverse events (AEs) that were possibly/probably/definitely related to study drugs were assessed in the determination of tolerance. Good treatment tolerance is defined as no AEs or only AEs possibly/probably/definitely related to study drugs graded 1 or 2 based on the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5). Poor treatment tolerance is defined as AEs possibly/probably/definitely related to study drugs graded 3 to 5 based on the CTCAE v5.
Summary of Outcome:
- The iDSMB and TSC have reviewed the Interim analysis results and recommended and agreed that the FORMaT trial is to continue the current Intensive Therapy Treatment Arms (Arms A, B and C) without modification.
- The new intensive Arm-D will be added as a 4th arm to the existing 3 intensive therapy arms. Arm-D includes IV sulbactam-durlobactam, IV ceftriaxone, oral amoxicillin, oral azithromycin and oral clofazimine.
Next Steps:
- The study will continue in accordance with the current approved protocol.
- Protocol amendments for the new Arm-D will be submitted to relevant regulatory authorities, ethics committees and site-specific governance.
- Allocation to Arm-D will be increased initially to equalise numbers as rapidly as possible – the allocation ratio will be calculated at the end of 2026. The roll out of Arm-D will be staggered across sites starting in Quarter 1 of 2027.