ICoN-1 Phase 3 Study of the Efficacy and Safety of Treatment With MNKD-101, Clofazimine Inhalation Suspension
NCT ID: NCT06418711
Last Updated: 2025-11-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE3
132 participants
INTERVENTIONAL
2024-09-11
2025-11-10
Brief Summary
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Detailed Description
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An open label extension study (Part B) will be offered to qualified participants for treatment with Clofazimine Inhalation Suspension.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Sputum Test Results: Results of post-baseline testing for the presence of NTM in sputum will remain concealed until the participant has completed Part A of the study and the participant's result for the sample taken at the end of Month 6 becomes available.
Study Groups
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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
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.
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.
Placebo
Eligible participants will be randomized in a 2:1 ratio to 1 of 2 possible treatment assignments, Clofazimine Inhalation Suspension or Placebo.
Interventions
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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.
Placebo
Eligible participants will be randomized in a 2:1 ratio to 1 of 2 possible treatment assignments, Clofazimine Inhalation Suspension or Placebo.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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
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).
18 Years
85 Years
ALL
No
Sponsors
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Mannkind Corporation
INDUSTRY
Responsible Party
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Principal Investigators
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Wassim Fares, MD
Role: STUDY_DIRECTOR
Mannkind Corporation
Locations
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University of Alabama at Birmingham School of Medicine
Birmingham, Alabama, United States
University of California San Francisco Fresno
Fresno, California, United States
Cedars-Sinai Medical Center
Los Angeles, California, United States
Hoag Hospital
Newport Beach, California, United States
University of California Davis Medical Center
Sacramento, California, United States
University of California San Francisco
San Francisco, California, United States
Santa Barbara Cottage Hospital
Santa Barbara, California, United States
Stanford University
Stanford, California, United States
National Jewish Health
Denver, Colorado, United States
UCONN Health
Farmington, Connecticut, United States
Yale University
New Haven, Connecticut, United States
Georgetown University Hospital
Washington D.C., District of Columbia, United States
The George Washington University Medical Faculty Associates
Washington D.C., District of Columbia, United States
VA Bay Pines
Bay Pines, Florida, United States
St. Francis Sleep, Allergy & Lung Institute
Clearwater, Florida, United States
Malcolm Randall Veterans Affairs Medical Center
Gainesville, Florida, United States
University of Florida College of Medicine
Jacksonville, Florida, United States
Theia Clinical Research
St. Petersburg, Florida, United States
University of South Florida
Tampa, Florida, United States
Midway Specialty Care Center
West Palm Beach, Florida, United States
Cleveland Clinic
Weston, Florida, United States
Flourish Research
Winter Park, Florida, United States
Emory University School Of Medicine
Atlanta, Georgia, United States
Medster Research
Valdosta, Georgia, United States
University of Hawaii
Honolulu, Hawaii, United States
University of Iowa Hospital and Clinics
Iowa City, Iowa, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
Infectious Disease Consultants Clinical Research
Wichita, Kansas, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, United States
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Henry Ford Hospital
Detroit, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
University of Missouri
Columbia, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States
Rutgers New Jersey Medical School
Newark, New Jersey, United States
Northwell Health
New Hyde Park, New York, United States
NYU Langone Health
New York, New York, United States
Mount Sinai-National Jewish Respiratory Institute
New York, New York, United States
Columbia University
New York, New York, United States
NYC Health and Hospitals-Elmhurst
Queens, New York, United States
Montefiore Medical Center
The Bronx, New York, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Oregon Health & Science University
Portland, Oregon, United States
Temple Lung Center
Philadelphia, Pennsylvania, United States
Reading Hospital
West Reading, Pennsylvania, United States
AnMed Health
Anderson, South Carolina, United States
Low Country Infectious Diseases
Charleston, South Carolina, United States
Medical University of South Carolina
Charleston, South Carolina, United States
North Texas Infectious Diseases Consultants
Dallas, Texas, United States
The University of Texas Health Science Center
Tyler, Texas, United States
UVA Health Infectious Diseases Clinic
Charlottesville, Virginia, United States
Macquarie University Clinical Trials Unit
Sydney, New South Wales, Australia
Sunshine Coast University Hospital
Birtinya, Queensland, Australia
The Prince Charles Hospital
Brisbane, Queensland, Australia
Gallipoli Medical Research Foundation
Greenslopes, Queensland, Australia
Monash University Centre for Inflammatory Diseases
Cranbourne, Victoria, Australia
Alfred Health
Melbourne, Victoria, Australia
Royal Perth Hospital Respiratory Clinic
Perth, Western Australia, Australia
Royal Adelaide Hospital
Adelaide, , Australia
Concord Repatriation General Hospital
Concord, , Australia
Aso Iizuka Hospital
Fukuoka, , Japan
National Hospital Organization Fukuokahigashi Medical Center
Fukuoka, , Japan
Fukuoka University Hospital
Fukuoka, , Japan
Fukuoka University Chikushi Hospital
Fukuoka, , Japan
National Hospital Organization Omuta National Hospital
Fukuoka, , Japan
National Hospital Organization Shibukawa Medical Center
Gunma, , Japan
Himeji Medical Center
Hyōgo, , Japan
Ibarakihigashi National Hospital
Ibaraki, , Japan
Kameda Clinic
Kamogawa-shi, , Japan
SHOWA University Fujigaoka Hospital
Kanagawa, , Japan
Minami Kyoto Hospital
Kyoto, , Japan
Matsusaka Municipal Hospital
Matsusaka, , Japan
Sendai Kousei Hospital
Miyagi, , Japan
Nishiniigata Chuo Hospital
Niigata, , Japan
National Hospital Organization - Osaka Toneyama Medical Center
Osaka, , Japan
Saitama Prefectural Cardiovascular and Respiratory Center
Saitama, , Japan
National Hospital Organization Kinki-Chuo Chest Medical Center
Sakai, , Japan
Keio University Hospital
Shinjuku-ku, , Japan
National Hospital Organization Tenryu Hospital
Shizuoka, , Japan
Mutual Aid Associations Toranomon Hospital
Tokyo, , Japan
Toho University Omori Medical Center
Tokyo, , Japan
Center Hospital of the National Center for Global Health and Medicine
Tokyo, , Japan
Japanese Red Cross Musashino Hospital
Tokyo, , Japan
Japan Anti-Tuberculosis Association Fukujuji Hospital
Tokyo, , Japan
SHOWA University Northern Yokohama Hospital
Yokohama, , Japan
Chonnam National University Hospital
Gwangju, , South Korea
Seoul National University Hospital
Seoul, , South Korea
Severance Hospital
Seoul, , South Korea
Asan Medical Center
Seoul, , South Korea
Samsung Medical Center
Seoul, , South Korea
The Catholic University of Korea Seoul St.Mary's Hospital
Seoul, , South Korea
National Taiwan University Hospital
Hsinchu, , Taiwan
Kaohsiung Medical University Hospital
Kaohsiung City, , Taiwan
Taichung Veterans General Hospital
Taichung, , Taiwan
Taipei Veterans General Hospital
Taipei, , Taiwan
National Taiwan University Hospital
Taipei, , Taiwan
Countries
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Other Identifiers
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MKC-CI-002
Identifier Type: -
Identifier Source: org_study_id