Phase 3 study

Reproduced exactly, unedited. Written for researchers rather than for patients.

Eligibility criteria for the FORMaT trial can be applied at two levels:

1. Eligibility into the Intervention Program, or;
2. Eligibility into the Observational Cohort.

Potential participants can only be enrolled in either the Intervention Program or the Observational Cohort at any one time. Provided the eligibility criteria are met, potential participants may either:

1. Enrol directly into the Intervention Program, or;
2. Enrol into the Observational Cohort and transition into the Intervention Program once they satisfy the inclusion criteria for this program which can occur at any time during the trial.

Eligibility into the FORMaT trial will be assessed at screening. Observational Cohort participants who go on to meet the Intervention Program eligibility criteria can transition from the Observational Cohort to the Intervention Program.

INTERVENTION PROGRAM ELIGIBILITY (APPENDIX A) Potential participants are eligible for the Intervention Program (Appendix A) if the criteria below are met. Eligible participants with mixed NTM infections (slow growers + MABS) or with recurrence of MABS infection following completion of previous treatment will be eligible if they meet the inclusion and exclusion criteria listed below. For eligible participants with mixed NTM infections additional therapy combinations are available as detailed in the relevant appendices.

INTERVENTION PROGRAM INCLUSION CRITERIA

1. Positive MABS-PD diagnosis meeting all three American Thoracic Society clinical, radiological and microbiological diagnostic criteria for MABS-PD. Defined as:

   1. Clinical: Pulmonary symptoms and exclusion of other diagnoses.
   2. Radiological: Nodular or cavitary opacities on chest radiograph or a chest high-resolution computed tomography (HRCT) scan showing multifocal bronchiectasis with multiple small nodules.
   3. Microbiological: MABS positive culture results from at least two separate expectorated sputum samples.

   or Positive culture results from at least one bronchial wash or lavage. or Transbronchial or other lung biopsy with mycobacterial histopathologic features (granulomatous inflammation or acid-fast bacilli (AFB)) and positive culture for NTM or biopsy showing mycobacterial histopathologic features (granulomatous inflammation or AFB) and one or more sputum or bronchial washes that are culture positive for NTM.

   Screening samples must be collected within the timeframes stated in the relevant appendix.

2. Male or female participants of any age.

3. Participant has not received treatment for MABS-PD in the 12 months preceding assessment of eligibility or as specified in the relevant appendix (this includes drugs prescribed for the treatment of other mycobacteria and/or other indications that may have activity against MABS, as specified in the FORMaT Prohibited Drug List Standard Operating Procedure (SOP)).

4. Informed consent signed by participant or parent/legal guardian if participant is under 18 years of age.

5. Ability to comply with study visits, therapies and study procedures as judged by the site investigator.

INTERVENTION PROGRAM EXCLUSION CRITERIA

• Participants receiving current treatment for MABS (this includes drugs prescribed for the treatment of other mycobacteria and/or other indications that may have activity against MABS, as specified in the FORMaT Prohibited Drug List SOP), except for participants taking azithromycin as part of routine treatment for CF or chronic infection-related pulmonary disease, or as specified in the relevant appendix.
• Participants who have a QTc interval of >500 milliseconds (QT interval corrected based on Fridericia method).
• Participants who are pregnant or planning to continue breast feeding.
• Known hypersensitivity or contraindication to any of the therapies for which no alternative option(s) have been provided.

OBSERVATIONAL COHORT INCLUSION CRITERIA

To be eligible to participate in the Observational Cohort the following criteria must be met:

1. Male and female participants of any age with at least one positive respiratory culture for MABS.
2. Informed consent signed by participant or parent/legal guardian if participant is under 18 years of age.
3. Ability to comply with study visits and study procedures as judged by the site investigator.

OBSERVATIONAL COHORT EXCLUSION CRITERIA

Potential participants will be ineligible to participate in the Observational Cohort if any of the following criterion are met:

• Receiving active treatment for MABS within the previous 12 months (this includes drugs prescribed for the treatment of other mycobacteria and/or other indications that may have activity against MABS, as specified in the FORMaT Prohibited Drug List SOP, except for participants taking azithromycin as part of routine treatment for CF or chronic infection-related pulmonary disease).

ADDITIONAL ELIGIBILITY CRITERIA Mixed NTM infections Participants who have cultured slow growing NTM of the same species two or more times in the 24 months prior to screening, with one of those cultures within the 6 months prior to screening, will be considered to have mixed NTM infection at the time of screening. The participants must meet all other inclusion criteria and no exclusion criteria to be eligible for participation. Ethambutol may be used in addition to trial therapies to cover mixed NTM infections considered to require treatment by their clinician.

Appendix specific sub-studies and integrated studies Appendix specific sub-studies and integrated studies may have additional eligibility criteria which are described in each of the relevant appendices.