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

Mycobacterium abscessus pulmonary disease (MABS-PD) is a rare and serious lung infection that affects people who already have lung problems such as bronchiectasis, cystic fibrosis, past tuberculosis, or weakened immune systems, as well as people who do not have pre-existing lung problems. This infection is becoming more common worldwide and is difficult to treat because it is highly resistant to many antibiotics. Current treatment usually lasts 12-18 months, is hard for patients to tolerate, and often causes significant side effects.

This study will test a new combination of antibiotics given during the first four weeks of treatment-the "intensive phase." The new regimen includes intravenous sulbactam-durlobactam and intravenous ceftriaxone, along with oral amoxicillin, oral azithromycin, and oral clofazimine. The trial will compare this new approach to the current standard-of-care therapy using the existing FORMaT adaptive platform trial, which was created to identify better treatments for MABS-PD.

The main goal of the study is to find out whether the new combination can clear the infection while also being easier for patients to tolerate. Additional study measures will look at lung function, chest imaging, quality of life, and health-care use. The trial also includes several research components that will examine how the drugs behave in the body, immune responses, mycobacterial genetics, and antibiotic resistance.

This innovative study aims to provide the first high-quality clinical evidence for a potentially more effective and less toxic treatment option for people living with this challenging and severe lung infection.

• Probability of MABS clearance at Final Outcome irrespective of toxicity according to participant's treatment pathway. [Срок оценки: Screening (Day 0); at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).]
• Incidence of Treatment emergent adverse events [Срок оценки: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).]
• Safety of treatments based on changes in microbiological resistance. [Срок оценки: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).]
• Change in Forced Expiratory Volume in 1 second (FEV1) z-score at Final Outcome compared with Screening in participants who do and do not clear MABS at Final Outcome. [Срок оценки: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).]
• Phenotype of the structural abnormalities of chest Computer Tomography (CT) and changes in chest CT scores between Screening and Final Outcome between participants who clear or do not clear MABS at Final Outcome. [Срок оценки: Screening (Day 0); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).]
• Predictive value of structural abnormalities on Screening CT scans for sputum conversion and for progression of structural changes in relation to treatment. [Срок оценки: Screening (Day 0); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).]
• Change in 6-minute walk distance (6MWD) for adult participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. [Срок оценки: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).]
• Change in HRQoL (measured using the Cystic Fibrosis Questionnaire - Respiratory domain (CFQ-R)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. [Срок оценки: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).]
• Change in HRQoL (measured using the EuroQol 5-Dimension (EQ-5D)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. [Срок оценки: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).]
• Change in HRQoL (measured using the St George's Respiratory Questionnaire (SGRQ)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. [Срок оценки: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).]
• Change in HRQoL (measured using the Short Form (SF-36)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. [Срок оценки: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).]
• Change in HRQoL (measured using the Pediatric Quality of Life Inventory (PedsQL)) for participants from Screening to Final Outcome according to treatment pathway and in participants who do and do not clear MABS at Final Outcome. [Срок оценки: Screening (Day 0); At End of Short Intensive Therapy (Week 6); At End of Prolonged Intensive Therapy OR at Week 12 visit; at End of Treatment plus 4 weeks off treatment (Final Outcome Visit - either Week 56 or Week 62).]