ICoN-1 Phase 3 Study of the Efficacy and Safety of Treatment With MNKD-101, Clofazimine Inhalation Suspension

Inclusion Criteria:

1. Evidence of signed and dated informed consent document(s) indicating the participanthas been informed of all pertinent aspects of the trial.

2. Age ≥18 years or legal age for the participating country (e.g., the legal age inSouth Korea is 19 years) and ≤85 years.

3. Evidence of underlying nodular bronchiectasis and/or fibrocavitary disease on achest radiograph or chest computed tomography, as determined by the investigator,within the last 12 months.

4. MAC-positive culture results from at least two separates (at least 1 week apart)expectorated sputum samples, one taken within 12 months, and another taken within 3months prior to the date of informed consent. Note: A sputum culture will beobtained at baseline, but the participant may be randomized prior to availability ofthe results.

5. Be able to produce at least 3 mL of sputum or be willing to undergo an inductionthat produces at least 3 mL of sputum for mycobacteriology.

6. FEV1 ≥40% of predicted during screening, as calculated by the local spirometrylaboratory standards.

7. Currently receiving a multi-drug regimen of GBT for pulmonary NTM infection in linewith the 2020 ATS/ERS/ESCMID/IDSA guideline for the treatment of NTM pulmonarydisease for at least 6 months prior to consenting in this study, with no changes inthis regimen within 2 months of screening.

8. For female participants of childbearing potential, a negative serum pregnancy testand agreement to use a protocol-recommended method of contraception duringheterosexual intercourse from the start of the screening period until ≥12 monthsafter the final dose of study therapy. Note: A female participant is considered tobe of childbearing potential, i.e., fertile, following menarche and until becomingpost-menopausal unless permanently sterile. Permanent sterilization methods includehysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausalstate is defined as no menses for 12 months without an alternative medical cause. Ahigh follicle-stimulating hormone (FSH) level in the postmenopausal range may beused to confirm a post-menopausal state in women not using hormonal contraception orhormonal replacement therapy. However, in the absence of 12 months of amenorrhea, asingle FSH measurement is insufficient.

9. For male participants who can father a child and are having intercourse with femalesof childbearing potential, agreement to use a protocol-recommended method ofcontraception from the start of the study therapy until ≥12 months after the finaldose of study therapy and to refrain from sperm donation from the start of studytherapy until ≥12 months after administration of the final dose of study therapy.Note: A male participant is considered fertile after puberty unless permanentlysterile by bilateral orchidectomy.

10. Willingness and ability to comply with scheduled visits, drug inhalation plan, studyprocedures, laboratory tests, and study restrictions.

Exclusion Criteria:

1. Cystic fibrosis.

2. Active tuberculosis. Note: Participants with a history of treated latent or activetuberculosis may be eligible as long as their sputum cultures in the last year arenegative for tuberculosis and they are deemed by the investigator as not havingcurrent active tuberculosis.

3. Disseminated MAC or MABSC infection or participants with isolated MABSC infection.

4. Recent (i.e., within the last 3 months from date of screening) ICU admission with orwithout mechanical ventilation.

5. Inability to inhale with a nebulizer, in the opinion of the investigator.

6. Participants with known hypersensitivity to any of the ingredients or excipients ofclofazimine.

7. Prior therapy with clofazimine in the previous 4 months from date of screening.

8. Participants with known resistance to clofazimine as treatment for MAC (i.e., MIC >8ug/mL for MAC).

9. Prior therapy with amikacin by any route of administration (e.g., inhaled or IV) inthe previous 2 months from date of screening.

10. Ongoing participation in any other interventional drug or device clinical trial, orexposure to another investigational drug within 28 days prior to start of studytreatment. Note: For investigational therapies that have a prolonged half-life, acase-by-case assessment will be made regarding the required washout period prior tobeing eligible for this study.

11. Current (or planned during the study) pregnancy or breastfeeding.

12. QT prolongation during screening (450 ms or longer), and/or uncontrolled sinusrhythm (>110/minute).

13. Increased risk of proarrhythmia (e.g., recent [within 6 months] myocardialinfarction, stroke, heart failure decompensation or left ventricular ejection of <45%, ventricular arrhythmias, torsade de pointes, unstable angina, or high-degreeatrioventricular block).

14. A family history of sudden cardiac death, unexplained death, long-QT syndrome, ordeath from a primary dysrhythmia potentially associated with QT prolongation.

15. Recent (within 6 months) initiation of or change in the dosing regimen of anyconcomitant medication that is known to prolong the QT interval. Note: Participantswho are on a stable regimen, in the opinion of the investigator, of the concomitantmedication during screening are eligible.

16. Chronic and clinically meaningful, in the opinion of the investigator, abnormalitiesin potassium, magnesium, or calcium levels.

17. Active pulmonary malignancy (primary or metastatic) or any malignancy requiringchemotherapy or radiation therapy within 3 years before screening or anticipatedduring the study period.

18. Current alcohol, medication, or illicit drug abuse.

19. Prior or ongoing social or medical condition (e.g., concomitant illness, psychiatriccondition, behavioral disorder), medical history, physical findings, ECG findings orlaboratory abnormality that, in the opinion of the investigator, could adverselyaffect the safety of the participant, makes it unlikely that the course treatment orfollow-up would be completed, or could impair the assessment of study results.

20. Any prior use of bedaquiline within 1 year of screening.

21. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 times upperlimit of normal (ULN) or total bilirubin >1.5 times ULN during screening.

22. Absolute neutrophil count <500/µL during screening.

23. Use of prednisone ≥10mg/day within 3 months prior to screening, or other significantimmunosuppression as deemed by the investigator.

24. Estimated glomerular filtration rate <30mL/minute/1.73 m2 (according to the CKD-EPI 2021 creatine equation) during screening.

25. Advanced liver disease (Child-Pugh Class A, B, or C).