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

ICoN-1: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of the Efficacy and Safety of Clofazimine Inhalation Suspension When Added to Guideline-Based Therapy in Participants With Nontuberculous Mycobacterial Infection

This clinical trial is designed to compare the efficacy and safety of Clofazimine Inhalation Suspension versus placebo when added to guideline-based therapy (GBT)

Study Overview

• Status: Terminated
• Conditions: Mycobacterium Infections, Nontuberculous; MAC Lung Disease; Treatment Refractory MAC Lung Disease
• Intervention / Treatment: Drug: Clofazimine Inhalation Suspension; Drug: Placebo

Detailed Description

Randomized, double-blind, placebo-controlled study (Part A) designed to compare the efficacy and safety of Clofazimine Inhalation Suspension versus placebo when added to guideline-based therapy (GBT). The primary objective of this study will be to compare the efficacy of Clofazimine Inhalation Suspension versus placebo as assessed by the co-primary endpoints, sputum culture conversion and change in Quality of Life-Bronchiectasis Respiratory Symptoms Score (QoL-B RSS).

An open label extension study (Part B) will be offered to qualified participants for treatment with Clofazimine Inhalation Suspension.

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital
  • Concord, Australia
    • Concord Repatriation General Hospital
  • New South Wales
    • Sydney, New South Wales, Australia, 2109
      • Macquarie University Clinical Trials Unit
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Sunshine Coast University Hospital
    • Brisbane, Queensland, Australia, 4032
      • The Prince Charles Hospital
    • Greenslopes, Queensland, Australia, 4064
      • Gallipoli Medical Research Foundation
  • Victoria
    • Cranbourne, Victoria, Australia, 3977
      • Monash University Centre for Inflammatory Diseases
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital Respiratory Clinic
• Japan
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Fukuoka, Japan, 818-8502
    • Fukuoka University Chikushi Hospital
  • Fukuoka, Japan, 837-0911
    • National Hospital Organization Omuta National Hospital
  • Fukuoka, Japan, 811-3195
    • National Hospital Organization Fukuokahigashi Medical Center
  • Fukuoka, Japan, 811-3195
    • Aso Iizuka Hospital
  • Gunma, Japan, 377-0280
    • National Hospital Organization Shibukawa Medical Center
  • Hyōgo, Japan, 670-8520
    • Himeji Medical Center
  • Ibaraki, Japan, 319-1113
    • Ibarakihigashi National Hospital
  • Kamogawa-shi, Japan, 296-0041
    • Kameda Clinic
  • Kanagawa, Japan, 227-8501
    • Showa University Fujigaoka Hospital
  • Kyoto, Japan, 610-0113
    • Minami Kyoto Hospital
  • Matsusaka, Japan, 515-8544
    • Matsusaka Municipal Hospital
  • Miyagi, Japan, 980-0873
    • Sendai Kousei Hospital
  • Niigata, Japan, 945-8585
    • Nishiniigata Chuo Hospital
  • Osaka, Japan, 560-8552
    • National Hospital Organization - Osaka Toneyama Medical Center
  • Saitama, Japan, 180-8610
    • Saitama Prefectural Cardiovascular and Respiratory Center
  • Sakai, Japan, 591-8555
    • National Hospital Organization Kinki-Chuo Chest Medical Center
  • Shinjuku-ku, Japan, 160-8582
    • Keio University Hospital
  • Shizuoka, Japan, 434-8511
    • National Hospital Organization Tenryu Hospital
  • Tokyo, Japan, 143-8541
    • Toho University Omori Medical Center
  • Tokyo, Japan, 180-8610
    • Japanese Red Cross Musashino Hospital
  • Tokyo, Japan, 162-8655
    • Center Hospital of the National Center for Global Health and Medicine
  • Tokyo, Japan, 105-8470
    • Mutual Aid Associations Toranomon Hospital
  • Tokyo, Japan, 204-8522
    • Japan Anti-Tuberculosis Association Fukujuji Hospital
  • Yokohama, Japan, 224-8503
    • Showa University Northern Yokohama Hospital
• South Korea
  • Gwangju, South Korea, 61469
    • Chonnam National University Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital
  • Seoul, South Korea, 06591
    • The Catholic University of Korea Seoul ST.MARY'S Hospital
• Taiwan
  • Hsinchu, Taiwan, 300
    • National Taiwan University Hospital
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Hospital
  • Taichung, Taiwan, 407219
    • Taichung Veterans General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham School of Medicine
  • California
    • Fresno, California, United States, 93701
      • University of California San Francisco Fresno
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Newport Beach, California, United States, 92663
      • Hoag Hospital
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • Santa Barbara, California, United States, 93105
      • Santa Barbara Cottage Hospital
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Connecticut
    • Farmington, Connecticut, United States, 06030-1225
      • UConn Health
    • New Haven, Connecticut, United States, 06520-8057
      • Yale University
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • The George Washington University Medical Faculty Associates
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Florida
    • Bay Pines, Florida, United States, 33744
      • VA Bay Pines
    • Clearwater, Florida, United States, 33765
      • St. Francis Sleep, Allergy & Lung Institute
    • Gainesville, Florida, United States, 32608
      • Malcolm Randall Veterans Affairs Medical Center
    • Jacksonville, Florida, United States, 32209
      • University of Florida College of Medicine
    • St. Petersburg, Florida, United States, 33707
      • Theia Clinical Research
    • Tampa, Florida, United States, 33620
      • University of South Florida
    • West Palm Beach, Florida, United States, 33401
      • Midway Specialty Care Center
    • Weston, Florida, United States, 33331
      • Cleveland Clinic
    • Winter Park, Florida, United States, 32789
      • Flourish Research
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Emory University School of Medicine
    • Valdosta, Georgia, United States, 31605
      • Medster Research
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital and Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Wichita, Kansas, United States, 67211
      • Infectious Disease Consultants Clinical Research
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Ochsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School Of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Columbia, Missouri, United States, 65201
      • University of Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School
  • New York
    • New Hyde Park, New York, United States, 11042
      • Northwell Health
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10016
      • NYU Langone Health
    • New York, New York, United States, 10029
      • Mount Sinai-National Jewish Respiratory Institute
    • Queens, New York, United States, 11373
      • NYC Health and Hospitals-Elmhurst
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7248
      • University of North Carolina at Chapel Hill
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple Lung Center
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Charleston, South Carolina, United States, 29414
      • Low Country Infectious Diseases
  • Texas
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consultants
    • Tyler, Texas, United States, 75708
      • The University of Texas Health Science Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • UVA Health Infectious Diseases Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Evidence of signed and dated informed consent document(s) indicating the participant has 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 in South Korea is 19 years) and ≤85 years.
3. Evidence of underlying nodular bronchiectasis and/or fibrocavitary disease on a chest 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 3 months prior to the date of informed consent. Note: A sputum culture will be obtained at baseline, but the participant may be randomized prior to availability of the results.
5. Be able to produce at least 3 mL of sputum or be willing to undergo an induction that produces at least 3 mL of sputum for mycobacteriology.
6. FEV1 ≥40% of predicted during screening, as calculated by the local spirometry laboratory standards.
7. Currently receiving a multi-drug regimen of GBT for pulmonary NTM infection in line with the 2020 ATS/ERS/ESCMID/IDSA guideline for the treatment of NTM pulmonary disease for at least 6 months prior to consenting in this study, with no changes in this regimen within 2 months of screening.
8. For female participants of childbearing potential, a negative serum pregnancy test and agreement to use a protocol-recommended method of contraception during heterosexual intercourse from the start of the screening period until ≥12 months after the final dose of study therapy. Note: A female participant is considered to be of childbearing potential, i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
9. For male participants who can father a child and are having intercourse with females of childbearing potential, agreement to use a protocol-recommended method of contraception from the start of the study therapy until ≥12 months after the final dose of study therapy and to refrain from sperm donation from the start of study therapy until ≥12 months after administration of the final dose of study therapy. Note: A male participant is considered fertile after puberty unless permanently sterile by bilateral orchidectomy.
10. Willingness and ability to comply with scheduled visits, drug inhalation plan, study procedures, laboratory tests, and study restrictions.

Exclusion Criteria:

1. Cystic fibrosis.
2. Active tuberculosis. Note: Participants with a history of treated latent or active tuberculosis may be eligible as long as their sputum cultures in the last year are negative for tuberculosis and they are deemed by the investigator as not having current 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 or without 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 of clofazimine.
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 >8 ug/mL for MAC).
9. Prior therapy with amikacin by any route of administration (e.g., inhaled or IV) in the previous 2 months from date of screening.
10. Ongoing participation in any other interventional drug or device clinical trial, or exposure to another investigational drug within 28 days prior to start of study treatment. Note: For investigational therapies that have a prolonged half-life, a case-by-case assessment will be made regarding the required washout period prior to being 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 sinus rhythm (>110/minute).
13. Increased risk of proarrhythmia (e.g., recent [within 6 months] myocardial infarction, stroke, heart failure decompensation or left ventricular ejection of <45%, ventricular arrhythmias, torsade de pointes, unstable angina, or high-degree atrioventricular block).
14. A family history of sudden cardiac death, unexplained death, long-QT syndrome, or death from a primary dysrhythmia potentially associated with QT prolongation.
15. Recent (within 6 months) initiation of or change in the dosing regimen of any concomitant medication that is known to prolong the QT interval. Note: Participants who are on a stable regimen, in the opinion of the investigator, of the concomitant medication during screening are eligible.
16. Chronic and clinically meaningful, in the opinion of the investigator, abnormalities in potassium, magnesium, or calcium levels.
17. Active pulmonary malignancy (primary or metastatic) or any malignancy requiring chemotherapy or radiation therapy within 3 years before screening or anticipated during the study period.
18. Current alcohol, medication, or illicit drug abuse.
19. Prior or ongoing social or medical condition (e.g., concomitant illness, psychiatric condition, behavioral disorder), medical history, physical findings, ECG findings or laboratory abnormality that, in the opinion of the investigator, could adversely affect the safety of the participant, makes it unlikely that the course treatment or follow-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 upper limit 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 significant immunosuppression 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clofazimine Inhalation Suspension; MNKD-101 (Clofazimine Inhalation Suspension) is a micronized suspension with a concentration of 20 mg/mL. Study drug will be inhaled using the PARI breath-enhanced jet nebulizer system daily for 28 days in Cycle 1. Cycle 2 will commence after 56 days off treatment and resume daily for 28 days. Dose: 80 mg	Drug: Clofazimine Inhalation Suspension; Eligible participants will be randomized in a 2:1 ratio to 1 of 2 possible treatment assignments, Clofazimine Inhalation Suspension or Placebo.; Other Names: MNKD-101
Placebo Comparator: Placebo; The placebo is comprised of isotonic saline (0.9% weight/volume sodium chloride). Study drug will be inhaled using the PARI breath-enhanced jet nebulizer system daily for 28 days in Cycle 1. Cycle 2 will commence after 56 days off treatment and resume daily for 28 days.	Drug: Placebo; Eligible participants will be randomized in a 2:1 ratio to 1 of 2 possible treatment assignments, Clofazimine Inhalation Suspension or Placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Part A) Change in QoL-B RSS from baseline to end of Month 6 (Part A)	(Part A) Change in QoL-B RSS from baseline to end of Month 6 (Part A)	Baseline to end of Month 6
(Part A) Sputum culture conversion (i.e., 3 consecutive monthly sputum cultures negative for MAC) by the end of Month 6	(Part A) Sputum culture conversion (i.e., 3 consecutive monthly sputum cultures negative for MAC) by the end of Month 6 (Part A)	Baseline to the end of Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Part A) Change in 6-minute walk distance (6MWD) from baseline to the end of Month 6	(Part A) Change in 6-minute walk distance (6MWD) from baseline to the end of Month 6	Baseline to the end of Month 6
(Part A) Change in participant identified Most Bothersome Symptom (MBS) from baseline to the end of Month 6	(Part A) Change in participant identified Most Bothersome Symptom (MBS) from baseline to the end of Month 6	Baseline to the end of Month 6
(Part A) Change in response to the Patient Global Impression of Severity (PGI-S) questionnaire from baseline to the end of Month 6	(Part A) Change in response to the Patient Global Impression of Severity (PGI-S) questionnaire from baseline to the end of Month 6	Baseline to the end of Month 6
(Part A) Response to the Patient Global Impression of Change (PGI-C) questionnaire at the end of Month 6	(Part A) Response to the Patient Global Impression of Change (PGI-C) questionnaire at the end of Month 6	Baseline to the end of Month 6
(Part A) Time to a composite endpoint of pulmonary worsening, as defined by: all-cause mortality, respiratory-related hospitalization, or the requirement for parenteral (inhaled or IV) antibiotic use for NTM or other pneumonia treatment (Part A)	(Part A) Time to a composite endpoint of pulmonary worsening, defined as the occurrence of any of the following clinical events: all-cause mortality, respiratory-related (as determined by the investigator) hospitalization, or the requirement for parenteral (inhaled or IV) antibiotic use for NTM or other pneumonia treatment (Part A)	Baseline to the end of Month 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Part A) Time to sputum culture conversion in participants who achieve culture conversion by Month 6	(Part A) Time to sputum culture conversion in participants who achieve culture conversion by Month 6	End of Month 6
(Part A) Rate of respiratory-related (as defined by the investigator) hospitalization	(Part A) Rate of respiratory-related (as defined by the investigator) hospitalization	Baseline to end of Month 6
(Part A) All-cause mortality	(Part A) All-cause mortality	Baseline to end of Month 6
(Part A) Respiratory-related (as determined by the investigator) mortality	(Part A) Respiratory-related (as determined by the investigator) mortality	Baseline to end of Month 6
(Part A) Use of rescue medication (i.e., initiation of anti-mycobacterial medication that is recommended by the investigator due to a perception of lack of efficacy of study drug) for pulmonary NTM infection	(Part A) Use of rescue medication (i.e., initiation of anti-mycobacterial medication that is recommended by the investigator due to a perception of lack of efficacy of study drug) for pulmonary NTM infection	Baseline to end of Month 6
(Part A) Difference in days of absenteeism from work	(Part A) Difference in days of absenteeism from work	Baseline to end of Month 6
(Part A) Difference in hospitalization days	(Part A) Difference in hospitalization days	Baseline to end of Month 6
(Part A) Difference in number of emergency room visits	(Part A) Difference in number of emergency room visits	Baseline to end of Month 6
(Part A) Difference in number of urgent care visits	(Part A) Difference in number of urgent care visits	Baseline to end of Month 6
(Part A) Difference in number of unscheduled doctor visits	(Part A) Difference in number of unscheduled doctor visits	Baseline to end of Month 6
(Part A) Change in BMI from baseline to the end of Month 6	(Part A) Change in BMI from baseline to the end of Month 6	Baseline to end of Month 6
(Part A) Changes in other QoL-B questionnaire domain (Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden) scores from baseline to the end of Month 6	(Part A) Changes in other QoL-B questionnaire domain (Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden) scores from baseline to the end of Month 6	Baseline to the end of Month 6
(Part A) Changes in shortness of breath when sitting or at rest and when exercising from baseline to the end of Month 6, measured using stand-alone shortness of breath questionnaire	(Part A) Changes in shortness of breath when sitting or at rest and when exercising from baseline to the end of Month 6, measured using stand-alone shortness of breath questionnaire	Baseline to the end of Month 6
(Part A) Change in most severe symptom at baseline from baseline to the end of Month 6, measured using stand-alone shortness of breath questionnaire	(Part A) Change in most severe symptom at baseline from baseline to the end of Month 6, measured using stand-alone shortness of breath questionnaire	Baseline to the end of Month 6
(Part A) Rate of study drug discontinuations	(Part A) Rate of study drug discontinuations	Baseline to end of Month 6
(Part A) Rate of study drug dose reductions	(Part A) Rate of study drug dose reductions	Baseline to end of Month 6
(Part A) Rate of treatment-emergent adverse events (TEAEs)	(Part A) Rate of treatment-emergent adverse events (TEAEs)	Baseline to end of Month 6
(Part A) Rate of serious adverse events (SAEs)	(Part A) Rate of serious adverse events (SAEs)	Baseline to end of Month 6
(Part A) Rate of laboratory abnormalities	(Part A) Rate of laboratory abnormalities	Baseline to end of Month 6
(Part A) Rate of electrocardiogram (ECG) abnormalities	(Part A) Rate of electrocardiogram (ECG) abnormalities	Baseline to end of Month 6
(Part B) Adverse Events (AEs) related to inhalation intolerability	(Part B) Adverse Events (AEs) related to inhalation intolerability	Study Month 7 through Study Month 22
(Part B) AEs due to skin discoloration	(Part B) AEs due to skin discoloration	Study Month 7 through Study Month 22
(Part B) AEs due to QTc changes	(Part B) AEs due to QTc changes	Study Month 7 through Study Month 22
(Part B) Sputum culture conversion (i.e., 3 consecutive- monthly sputum cultures negative for NTM	(Part B) Sputum culture conversion (i.e., 3 consecutive- monthly sputum cultures negative for NTM	Study Month 7 through Study Month 22
(Part B) Rate of persistency of negative sputum culture	(Part B) Rate of persistency of negative sputum culture	Study Month 7 through Study Month 22
(Part B) Change in QoL-B RSS from baseline	(Part B) Change in QoL-B RSS from baseline	Study Month 7 through Study Month 22
(Part B) Difference in days of absenteeism from work	(Part B) Difference in days of absenteeism from work	Study Month 7 through Study Month 22
(Part B) Difference in hospitalization days	(Part B) Difference in hospitalization days	Study Month 7 through Study Month 22
(Part B) Difference in number of emergency room visits	(Part B) Difference in number of emergency room visits	Study Month 7 through Study Month 22
(Part B) Difference in number of urgent care visits	(Part B) Difference in number of urgent care visits	Study Month 7 through Study Month 22
(Part B) Difference in number of unscheduled doctor visits	(Part B) Difference in number of unscheduled doctor visits	Study Month 7 through Study Month 22
(Part B) Sustainability of response to Clofazimine Inhalation Suspension, evaluated quarterly while on treatment following initial conversion, for participants who convert	(Part B) Sustainability of response to Clofazimine Inhalation Suspension, evaluated quarterly while on treatment following initial conversion, for participants who convert. Culture conversion with sustainability is defined as achieving culture conversion and then having no more than 2 consecutive broth or Agar positive sputum cultures and no Agar positive culture observed once initial conversion is achieved.	Study Month 7 through Study Month 22
(Part B) Durability of response to Clofazimine Inhalation Suspension, evaluated quarterly following active treatment, for participants who remain converters at the end of active treatment	(Part B) Durability of response to Clofazimine Inhalation Suspension, evaluated quarterly following active treatment, for participants who remain converters at the end of active treatment. Culture conversion with durability is defined as achieving culture conversion and remaining a converter at the end of active treatment and then having no broth or Agar positive sputum culture following active treatment	Study Month 7 through Study Month 22
(Part A) Sputum MAC density in CFU/mL at the end of Month 6	(Part A) Sputum MAC density in CFU/mL at the end of Month 6	End of Month 6
(Part A) Sputum MAC resistance patterns at the end of Month 6, measured using sputum microbiological lab assessments	(Part A) Sputum MAC resistance patterns at the end of Month 6, measured using sputum microbiological lab assessments	End of Month 6
(Part A) Time to first negative MAC sputum culture in participants who achieve culture conversion by Month 6	(Part A) Time to first negative MAC sputum culture in participants who achieve culture conversion by Month 6	End of Month 6
(Part A) Rate of sputum culture conversion (MAC-negative to MAC-positive) in the subgroup of study participants whose baseline sputum culture is negative for NTM	(Part A) Rate of sputum culture conversion (MAC-negative to MAC-positive) in the subgroup of study participants whose baseline sputum culture is negative for NTM	Baseline to end of study
(Part A) Time-to-positivity (TTP) in broth cultures for MAC in sputum at the end of Months 1,2,3,4,5, and 6	(Part A) Time-to-positivity (TTP) in broth cultures for MAC in sputum at the end of Months 1,2,3,4,5, and 6	End of Months 1,2,3,4,5, and 6
(Part A) Changes in inflammatory markers (specific tests to be determined) from baseline to the end of Months 1,3,4, and 6	(Part A) Changes in inflammatory markers (specific tests to be determined) from baseline to the end of Months 1,3,4, and 6	End of Months Months 1,3,4, and 6
(Part A) Rate of pulmonary worsening, as diagnosed and defined by the investigator based upon a participant's need for a limited course of antibiotic medication to treat an acute worsening of symptoms, in Months 1,2,3,4,5, and 6	(Part A) Rate of pulmonary worsening, as diagnosed and defined by the investigator based upon a participant's need for a limited course of antibiotic medication to treat an acute worsening of symptoms, in Months 1,2,3,4,5, and 6	End of Months 1,2,3,4,5, and 6
(Part A) Slope of the change from baseline to end of Month 6 in log10 CFU/mL of MAC	(Part A) Slope of the change from baseline to end of Month 6 in log10 CFU/mL of MAC	Baseline to end of Month 6
(Part A) Concentration of clofazimine in plasma	(Part A) Concentration of clofazimine in plasma	Baseline to end of Month 6
(Part A) Change in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) from baseline to the end of Month 6	(Part A) Change in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) from baseline to the end of Month 6	Baseline to the end of Month 6
(Part A) Rate of treatment-related adverse events (TRAEs)	(Part A) Rate of treatment-related adverse events (TRAEs)	Baseline to end of Month 6
(Part B) Rate of sputum culture conversion (MAC-negative to MAC-positive) in the subgroup of study participants whose baseline sputum culture is negative	(Part B) Rate of sputum culture conversion (MAC-negative to MAC-positive) in the subgroup of study participants whose baseline sputum culture is negative	Study Month 7 through Study Month 22

Collaborators and Investigators

• Sponsor: Mannkind Corporation
• Investigators: Study Director: Wassim Fares, MD, Mannkind Corporation

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2024
• Primary Completion (Actual): November 10, 2025
• Study Completion (Actual): November 10, 2025

Study Registration Dates

• First Submitted: May 8, 2024
• First Submitted That Met QC Criteria: May 13, 2024
• First Posted (Actual): May 17, 2024

Study Record Updates

• Last Update Posted (Actual): November 12, 2025
• Last Update Submitted That Met QC Criteria: November 10, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Bacterial Infections; Mycobacterium avium-intracellulare Infection; Azithromycin; Bronchiectasis; Infections; Ethambutol; Amikacin; Mycobacteria; Respiratory Infection; Lung diseases; Antitubercular Agents; Anti-Bacterial Agents; Bacterial Infections and Mycoses; antimycobacterial activity; antimycobacterial therapy; MAC infections; MAC pulmonary infection; mycobacterium; Mycobacterium Avium Complex Infections; Mycobacterium avium complex lung disease; Nontuberculous; Non-tuberculous mycobacterial (NTM) infections; Nontuberculous mycobacterial lung disease; NTM infection; NTM lung disease; NTM Pulmonary Disease; NTM lung infection; Pulmonary MAC disease; Pulmonary Mycobacterium Avium Complex disease; Treatment refractory MAC lung disease; Treatment refractory mycobacterial lung disease; Treatment refractory NTM lung infection; Treatment refractory NTM pulmonary disease; Clofazimine; Gram-Positive Bacterial Infections; Anti-infective Agents; Mycobacterium Infections, Nontuberculous; Actinomycetales Infections; Respiratory Tract diseases; NTM (Nontuberculous mycobacteria); MAC (Mycobacterium avium complex); MABSC (Mycobacterium abscessus complex); Pulmonary Nontuberculous Mycobacteria; MAC Lung disease; mycobacterium Infections; Non-tuberculous mycobacterial pulmonary disease; Lamprene
• Additional Relevant MeSH Terms: Bronchial Diseases; Lung Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Mycobacterium avium-intracellulare Infection; Bronchiectasis; Bacterial Infections; Gram-Positive Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: MKC-CI-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No