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

Summary

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.

Conditions

• Mycobacterium Abscessus Pulmonary Disease
• Mycobacterium Abscessus Infection
• Non-Tuberculous Mycobacterial (NTM) Infections
• Non-Tuberculous Mycobacteria Pulmonary Disease

Interventions

DRUG

Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours)

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.

DRUG

Ceftriaxone for Injection

Adults and Children 12 years and older: IV ceftriaxone 1g Every TWELVE (12) hourly

DRUG

Amoxicillin

Adults and Children 12 years and older: Oral amoxicillin 1000mg Three times daily

DRUG

Azithromcyin

Adults and Children 12 years and older: Oral Azithromycin 250 - 500mg Once daily If \<40kg or poorly tolerated 250mg Once daily

DRUG

clarithromycin

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

DRUG

Clofazimine

Adults and Children 12 years and older: Oral clofazimine 100mg to 300mg Once daily

DRUG

Ethambutol

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

DRUG

Amikacin Injection

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

DRUG

tigecycline

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

DRUG

Imipenem + Cilastatin

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).

DRUG

Cefoxitin

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.

DRUG

Amikacin (Inhalation)

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.

DRUG

linezolid

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.

DRUG

Trimethoprim / Sulfamethoxazole

Adults and children 12 years and older: Oral Co-trimoxazole (Trimethoprim / Sulfamethoxazole) 160/800mg twice daily.

DRUG

Doxycycline

Adults and Children 12 years and older: Oral doxycycline 100mg once daily.

DRUG

moxifloxacin

Adult: Oral moxifloxacin 400mg once daily. Children 12 years and older: Oral moxifloxacin 10-15mg/kg once daily, maximum dose 400mg

DRUG

bedaquiline

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).

DRUG

Rifabutin

Adult: Oral rifabutin: 5mg/kg once daily, maximum 300-450mg. Children 12 years and older: Oral rifabutin 5mg/kg once daily

Sponsors & Collaborators

• Innoviva Specialty Therapeutics

  collaborator INDUSTRY

• The University of Queensland

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2027-04-30

Primary Completion

2031-04-30

Completion

2031-07-31

FDA Drug

Yes