Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT07485010 | Testing a Novel Combination Treatment (Arm D) Versus Standard of Care for Intensive Phase Treatment for Mycobacterium Abscessus Pulmonary Disease in People With or Without Cystic Fibrosis in the Finding the Optimal Regimen for Mycobacterium Abscessus Treatment (FORMaT) Adaptive Platform Trial | PHASE2 | NOT YET_RECRUITING | 300 | — | — | Apr 1, 2027 | Jul 1, 2031 | Mar 20, 2026 | - | — |
Definition of MABS clearance at final outcome: Negative MABS cultures from four consecutive sputum samples with one of those sputum specimens collected four weeks after the completion of consolidation therapy, or a MABS negative Bronchoalveolar Lavage (BAL) collected four weeks after completion of consolidation. Definition of tolerance: Tolerance is based on the Common Terminology Criteria for Adverse Events (CTCAE version 5.0). Only adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drug will be assessed in the determination of tolerance. "Good" tolerance is defined as no adverse events occurring or only adverse events coded as CTCAE grades 1 and 2. "Poor" tolerance is defined as any adverse events attributed as possibly-, probably-, or definitely-related to study drug coded as CTCAE grades 3, 4, or 5.
Microbiological clearance of MABS from respiratory samples collected at 4 weeks with good tolerability assessed at the end of short intensive therapy between Arm D and the standard of care arms given during intensive phase. Definition of MABS clearance is 3 MABS negative sputum samples or ONE MABS negative Bronchoalveolar Lavage (BAL) at end of Short Intensive Therapy. Treatment tolerance is defined as no Treatment emergent adverse events and/or Treatment emergent adverse events that are "possibly-", "probably-", or "definitely-" related to study drug and coded as grade 1 or 2 based on the CTCAEv5.0.
To compare the microbiological clearance from samples collected at 10 weeks with good tolerability between those who are allocated to prolonged intensive therapy and those allocated to immediate consolidation following short intensive therapy. MABS clearance, assessed at the end of prolonged intensive therapy (for those allocated to prolonged intensive) or at 12 weeks (for those allocated to immediate consolidation) will be defined as negative MABS cultures from all 3 sputum samples or from one BAL sample collected at 10 weeks. "Good" tolerance is defined as no adverse events occurring or only adverse events that are attributed as either "possibly-", "probably-", or "definitely-" related to study drug coded as CTCAE grades 1 and 2.
| Arm | Type | Description |
|---|---|---|
| Intensive Arm D with Sulbactam-Durlobactam in a combination antibiotic regimen | EXPERIMENTAL | Weeks 1 to 4 (and Weeks 7 to 10 if randomised to Prolonged Intensive) 1. IV sulbactam-durlobactam 2. IV ceftriaxone 3. Oral amoxicillin 4. Oral azithromycin or clarithromycin 5. Oral clofazimine. Weeks 5 to 6 (and Weeks 8 to 12 if randomised to Prolonged Intensive) 1\. Oral clofazimine, and; 2. Oral azithromycin or clarithromycin, and; 3. In combination with one to three of the following oral antibiotics guided by participant susceptibility and tolerance: * Linezolid, * Trimethoprim / sulfamethoxazole (co-trimoxazole), * Bedaquiline, * Rifabutin, * Doxycycline, * Moxifloxacin. |
| Intensive Arm A with IV amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine | ACTIVE_COMPARATOR | 1. IV amikacin, and; 2. IV tigecycline, and; 3. IV imipenem/cilastatin or IV cefoxitin, and; 4. Oral azithromycin or oral clarithromycin, and; 5. Oral clofazimine. Administered for a duration of 6 weeks for Short Intensive Therapy or 12 weeks for Prolonged Intensive Therapy. |
| Intensive Arm B with Inhaled Amikacin, imipenem or cefoxitin, tigecycline, macrolide and clofazimine | EXPERIMENTAL | 1. Inhaled amikacin, and; 2. IV tigecycline, and; 3. IV imipenem/cilastatin or IV cefoxitin, and; 4. Oral azithromycin or oral clarithromycin, and; 5. Oral clofazimine. Administered for a duration of 6 weeks for Short Intensive Therapy or 12 weeks for Prolonged Intensive Therapy. |
| Intensive Arm C with IV amikacin, imipenem or cefoxitin, tigecycline and macrolide | EXPERIMENTAL | 1. IV amikacin, and; 2. IV tigecycline, and; 3. IV imipenem/cilastatin or IV cefoxitin, and; 4. Oral azithromycin or oral clarithromycin. Administered for a duration of 6 weeks for Short Intensive Therapy or 12 weeks for Prolonged Intensive Therapy. |
| Consolidation arm a with clofazimine, macrolide and a combination of 1 to 3 oral antibiotic agents | ACTIVE_COMPARATOR | Oral clofazimine + oral azithromycin/oral clarithromycin in combination with one to three of the following oral antibiotics: oral linezolid, oral co-trimoxazole, oral doxycycline, oral moxifloxacin, oral bedaquiline (adults only), oral rifabutin. For 46 weeks after completion of Intensive Therapy phase. |
| Consolidation arm b with inhaled amikacin, clofazimine, macrolide and 1 to 3 oral antibiotic agents | EXPERIMENTAL | Inhaled amikacin (IA), oral clofazimine + oral azithromycin/oral clarithromycin in combination with one to three of the following oral antibiotics: oral linezolid, oral co-trimoxazole, oral doxycycline, oral moxifloxacin, oral bedaquiline (adults only), oral rifabutin. For 46 weeks after completion of Intensive Therapy phase. |
| Name | Type | Description |
|---|---|---|
| Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours) | DRUG | Adults and Children 12 years and older: IV sulbactam/durlobactam Greater than or equal to 130ml/min Every FOUR (4) hourly. Administered by intravenous infusion over 3 hours. For CrCL 45 to 129ml/min 1g sulbactam/ 1g durlobactam Every SIX (6) hourly. Administer by intravenous infusion over 3 hours. For CrCL 30 to 44ml/min 1g sulbactam/ 1g durlobactam Every EIGHT (8) hourly. Administer by intravenous infusion over 3 hours. For CrCL 15 to 29ml/min 1g sulbactam/ 1g durlobactam Every TWELVE (12) hourly. Administer by intravenous infusion over 3 hours. For CrCL\<15ml/min 1g sulbactam/ 1g durlobactam Every TWELVE (12) hourly for first 3 doses then reduce to every 24 hourly thereafter. Administer by intravenous infusion over 3 hours. |
| Ceftriaxone for Injection | DRUG | Adults and Children 12 years and older: IV ceftriaxone 1g Every TWELVE (12) hourly |
| Amoxicillin | DRUG | Adults and Children 12 years and older: Oral amoxicillin 1000mg Three times daily |
| Azithromcyin | DRUG | Adults and Children 12 years and older: Oral Azithromycin 250 - 500mg Once daily If \<40kg or poorly tolerated 250mg Once daily |
| clarithromycin | DRUG | Oral clarithromycin. Only for use if azithromycin not tolerated. Adults: 500mg twice daily. Children: 12-18 years of age: Dosing independent of weight 500mg twice daily |
| Clofazimine | DRUG | Adults and Children 12 years and older: Oral clofazimine 100mg to 300mg Once daily |
| Ethambutol | DRUG | For participants with confirmed mixed NTM (slow growers + MABS) infections, there is an option to add oral ethambutol to the treatment arm in accordance with the dosing below. Oral ethambutol 15mg/kg (rounded to account for tablet strength) OR Once daily 25mg/kg (rounded to account for tablet strength) Thrice weekly |
| Amikacin Injection | DRUG | Adults: Intravenous amikacin 5mg/kg once daily or 7.5mg/kg twice daily or 20-25 mg/kg thrice weekly. Children: Intravenous amikacin 15-30 mg/kg once daily, maximum dose 1500mg |
| tigecycline | DRUG | Adults: Intravenous Tigecycline 25 mg increasing by 5 mg every two doses until either maximum dose reached (50mg) or until patient is unable to tolerate twice daily. Children (≥8 years of age) intravenous tigecycline: Day 1- 0.6mg/kg twice daily to a maximum of 25mg. Day 2- 0.6mg/kg (maximum 25mg) in the morning, 1.2 mg/kg (maximum 50mg) at night. Day 3- 1.2mg/kg (maximum 50 mg) twice daily |
| Imipenem + Cilastatin | DRUG | Adults: Intravenous Imipenem (≥50kg) 500mg twice daily (\<50kg) 15 mg/kg twice daily. Children: intravenous imipenem Day 1- 2- 25mg/kg (maximum 1g) twice daily. DAY 3- 25mg/kg (maximum 1g) four times daily (drop to 3 if not tolerated). |
| Cefoxitin | DRUG | Adults: If imipenem is poorly tolerated intravenous cefoxitin 200 mg/kg thrice daily. Children: if imipenem is poorly tolerated intravenous cefoxitin 50mg/kg (maximum 4g) four times daily. |
| Amikacin (Inhalation) | DRUG | Adult: Inhaled amikacin 500mg twice daily. Children: Inhaled amikacin 500mg twice daily. PLEASE NOTE: low preservative intravenous amikacin preparation to be used as inhalation, NOT liposomal amikacin. |
| linezolid | DRUG | Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral linezolid 600mg once daily. Children: \>12 years 600mg once daily. |
| Trimethoprim / Sulfamethoxazole | DRUG | Adults and children 12 years and older: Oral Co-trimoxazole (Trimethoprim / Sulfamethoxazole) 160/800mg twice daily. |
| Doxycycline | DRUG | Adults and Children 12 years and older: Oral doxycycline 100mg once daily. |
| moxifloxacin | DRUG | Adult: Oral moxifloxacin 400mg once daily. Children 12 years and older: Oral moxifloxacin 10-15mg/kg once daily, maximum dose 400mg |
| bedaquiline | DRUG | Adult: Oral bedaquiline (18-64 years of age) 400mg once daily for the first two weeks followed by 400mg thrice weekly for 22 weeks (maximum duration of 6 months). |
| Rifabutin | DRUG | Adult: Oral rifabutin: 5mg/kg once daily, maximum 300-450mg. Children 12 years and older: Oral rifabutin 5mg/kg once daily |
Inclusion Criteria: 1. Must meet eligibility criteria as per the FORMaT Master Protocol and Appendix A1 Inclusion Criteria (NCT04310930). 2. Male or female participants aged 12 years and older. Exclusion Criteria: 1. Must not have any exclusion criteria as per the FORMaT Master Protocol and Appen...