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

A Multi-centre, Randomised Trial Comparing a Novel Combination Treatment (Arm D - Intravenous Sulbactam-durlobactam in Combination With Intravenous Ceftriaxone, Oral Amoxicillin, Oral Azithromycin and Oral Clofazimine) Versus Standard of Care Treatments for the Intensive Phase of 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

The goal of this clinical trial is to learn if a new combination antibiotic treatment (Arm D) works to treat a rare lung condition called mycobacterium abscessus pulmonary disease in people of any age and sex, when compared to the standard treatments. It will also learn about the safety of this new combination antibiotic treatment when compared to the standard treatments. The main questions it aims to answer are:

• How well does Arm D treat mycobacterium abscessus pulmonary disease?
• What side effects does Arm D cause when used to treat mycobacterium abscessus pulmonary disease? Researchers will compare Arm D to the current standard of care treatments to see if Arm D treats mycobacterium abscessus pulmonary disease better and if it will cause less side effects.

Participants will:

• Be screened and recruited to the FORMaT adaptive platform trial (NCT04310930)
• Be given Arm D for 4 weeks or standard of care treatments for 6 weeks.
• Be reviewed by the study doctors weekly for checkups and tests.
• Provide respiratory samples (sample coughed up from the chest), respond to quality-of-life questionnaires, have CT lung scans and blood tests.

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.

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 Appendix A1 Exclusion Criteria (NCT04310930).

2. Participants aged <12 years old.

3. Participants aged between 12 and <18years old with clinically significant renal impairment as indicated by an age-appropriate estimated creatinine clearance.

4. Known hypersensitivity to any of the therapies for which no alternative option(s) have been provided. This includes:

   • Sulbactam/durlobactam
   • Ceftriaxone,
   • Amoxicillin,
   • Macrolide antibiotics, and
   • Clofazimine.