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

NCT06418711 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: MKC-CI-002
• Study Type: interventional
• Target: 132
• Locations: 5 countries
• Sites: 99

Brief Summary

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

Conditions

MAC Lung Disease; Treatment Refractory MAC Lung Disease; Mycobacterium Infections, Nontuberculous

Keywords

Bronchiectasis; NTM (Nontuberculous mycobacteria); MAC (Mycobacterium avium complex); MABSC (Mycobacterium abscessus complex); Pulmonary Nontuberculous Mycobacteria; Respiratory Infection; antimycobacterial activity; antimycobacterial therapy; MAC infections; MAC Lung disease; MAC pulmonary infection; Mycobacteria; mycobacterium; Mycobacterium Avium Complex Infections; Mycobacterium avium complex lung disease; mycobacterium Infections; Nontuberculous; Non-tuberculous mycobacterial (NTM) infections; Nontuberculous mycobacterial lung disease; Non-tuberculous mycobacterial pulmonary 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; Respiratory Tract diseases; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Mycobacterium Infections, Nontuberculous; Mycobacterium avium-intracellulare Infection; Lung diseases; Anti-Bacterial Agents; Anti-infective Agents; Antitubercular Agents; Azithromycin; Amikacin; Ethambutol; Clofazimine; Lamprene

Outcome Measures

Primary Outcomes (2)

• (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

• (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

Secondary Outcomes (5)

• (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)

  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

  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

  Baseline to the end of Month 6

Other Outcomes (45)

• (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

  End of Month 6

• (Part A) Time to first negative MAC sputum culture in participants who achieve culture conversion by Month 6

  End of Month 6

Study Arms (2)

Clofazimine Inhalation Suspension

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Clofazimine Inhalation Suspension DRUG

Eligible participants will be randomized in a 2:1 ratio to 1 of 2 possible treatment assignments, Clofazimine Inhalation Suspension or Placebo.

Also known as: MNKD-101

Clofazimine Inhalation Suspension

Placebo DRUG

Eligible participants will be randomized in a 2:1 ratio to 1 of 2 possible treatment assignments, Clofazimine Inhalation Suspension or Placebo.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Evidence of signed and dated informed consent document(s) indicating the participant has been informed of all pertinent aspects of the trial.
• Age ≥18 years or legal age for the participating country (e.g., the legal age in South Korea is 19 years) and ≤85 years.
• 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.
• 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.
• 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.
• FEV1 ≥40% of predicted during screening, as calculated by the local spirometry laboratory standards.
• 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.
• 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.
• 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.
• Willingness and ability to comply with scheduled visits, drug inhalation plan, study procedures, laboratory tests, and study restrictions.

You may not qualify if:

• Cystic fibrosis.
• 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.
• Disseminated MAC or MABSC infection or participants with isolated MABSC infection.
• Recent (i.e., within the last 3 months from date of screening) ICU admission with or without mechanical ventilation.
• Inability to inhale with a nebulizer, in the opinion of the investigator.
• Participants with known hypersensitivity to any of the ingredients or excipients of clofazimine.
• Prior therapy with clofazimine in the previous 4 months from date of screening.
• Participants with known resistance to clofazimine as treatment for MAC (i.e., MIC \>8 ug/mL for MAC).
• Prior therapy with amikacin by any route of administration (e.g., inhaled or IV) in the previous 2 months from date of screening.
• 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.
• Current (or planned during the study) pregnancy or breastfeeding.
• QT prolongation during screening (450 ms or longer), and/or uncontrolled sinus rhythm (\>110/minute).
• 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).
• A family history of sudden cardiac death, unexplained death, long-QT syndrome, or death from a primary dysrhythmia potentially associated with QT prolongation.
• 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.

Sponsors & Collaborators

• Mannkind Corporation: lead

Study Sites (99)

University of Alabama at Birmingham School of Medicine

Birmingham, Alabama, 35294, United States

Location

University of California San Francisco Fresno

Fresno, California, 93701, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Hoag Hospital

Newport Beach, California, 92663, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Santa Barbara Cottage Hospital

Santa Barbara, California, 93105, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

UCONN Health

Farmington, Connecticut, 06030-1225, United States

Location

Yale University

New Haven, Connecticut, 06520-8057, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

The George Washington University Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

VA Bay Pines

Bay Pines, Florida, 33744, United States

Location

St. Francis Sleep, Allergy & Lung Institute

Clearwater, Florida, 33765, United States

Location

Malcolm Randall Veterans Affairs Medical Center

Gainesville, Florida, 32608, United States

Location

University of Florida College of Medicine

Jacksonville, Florida, 32209, United States

Location

Theia Clinical Research

St. Petersburg, Florida, 33707, United States

Location

University of South Florida

Tampa, Florida, 33620, United States

Location

Midway Specialty Care Center

West Palm Beach, Florida, 33401, United States

Location

Cleveland Clinic

Weston, Florida, 33331, United States

Location

Flourish Research

Winter Park, Florida, 32789, United States

Location

Emory University School Of Medicine

Atlanta, Georgia, 30342, United States

Location

Medster Research

Valdosta, Georgia, 31605, United States

Location

University of Hawaii

Honolulu, Hawaii, 96813, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Infectious Disease Consultants Clinical Research

Wichita, Kansas, 67211, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70115, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Missouri

Columbia, Missouri, 65201, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Rutgers New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

Northwell Health

New Hyde Park, New York, 11042, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Mount Sinai-National Jewish Respiratory Institute

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

NYC Health and Hospitals-Elmhurst

Queens, New York, 11373, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7248, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Temple Lung Center

Philadelphia, Pennsylvania, 19140, United States

Location

Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

AnMed Health

Anderson, South Carolina, 29621, United States

Location

Low Country Infectious Diseases

Charleston, South Carolina, 29414, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

North Texas Infectious Diseases Consultants

Dallas, Texas, 75246, United States

Location

The University of Texas Health Science Center

Tyler, Texas, 75708, United States

Location

UVA Health Infectious Diseases Clinic

Charlottesville, Virginia, 22903, United States

Location

Macquarie University Clinical Trials Unit

Sydney, New South Wales, 2109, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, 4575, Australia

Location

The Prince Charles Hospital

Brisbane, Queensland, 4032, Australia

Location

Gallipoli Medical Research Foundation

Greenslopes, Queensland, 4064, Australia

Location

Monash University Centre for Inflammatory Diseases

Cranbourne, Victoria, 3977, Australia

Location

Alfred Health

Melbourne, Victoria, 3004, Australia

Location

Royal Perth Hospital Respiratory Clinic

Perth, Western Australia, 6000, Australia

Location

Royal Adelaide Hospital

Adelaide, 5000, Australia

Location

Concord Repatriation General Hospital

Concord, Australia

Location

Aso Iizuka Hospital

Fukuoka, 811-3195, Japan

Location

National Hospital Organization Fukuokahigashi Medical Center

Fukuoka, 811-3195, Japan

Location

Fukuoka University Hospital

Fukuoka, 814-0180, Japan

Location

Fukuoka University Chikushi Hospital

Fukuoka, 818-8502, Japan

Location

National Hospital Organization Omuta National Hospital

Fukuoka, 837-0911, Japan

Location

National Hospital Organization Shibukawa Medical Center

Gunma, 377-0280, Japan

Location

Himeji Medical Center

Hyōgo, 670-8520, Japan

Location

Ibarakihigashi National Hospital

Ibaraki, 319-1113, Japan

Location

Kameda Clinic

Kamogawa-shi, 296-0041, Japan

Location

SHOWA University Fujigaoka Hospital

Kanagawa, 227-8501, Japan

Location

Minami Kyoto Hospital

Kyoto, 610-0113, Japan

Location

Matsusaka Municipal Hospital

Matsusaka, 515-8544, Japan

Location

Sendai Kousei Hospital

Miyagi, 980-0873, Japan

Location

Nishiniigata Chuo Hospital

Niigata, 945-8585, Japan

Location

National Hospital Organization - Osaka Toneyama Medical Center

Osaka, 560-8552, Japan

Location

Saitama Prefectural Cardiovascular and Respiratory Center

Saitama, 180-8610, Japan

Location

National Hospital Organization Kinki-Chuo Chest Medical Center

Sakai, 591-8555, Japan

Location

Keio University Hospital

Shinjuku-ku, 160-8582, Japan

Location

National Hospital Organization Tenryu Hospital

Shizuoka, 434-8511, Japan

Location

Mutual Aid Associations Toranomon Hospital

Tokyo, 105-8470, Japan

Location

Toho University Omori Medical Center

Tokyo, 143-8541, Japan

Location

Center Hospital of the National Center for Global Health and Medicine

Tokyo, 162-8655, Japan

Location

Japanese Red Cross Musashino Hospital

Tokyo, 180-8610, Japan

Location

Japan Anti-Tuberculosis Association Fukujuji Hospital

Tokyo, 204-8522, Japan

Location

SHOWA University Northern Yokohama Hospital

Yokohama, 224-8503, Japan

Location

Chonnam National University Hospital

Gwangju, 61469, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea Seoul St.Mary's Hospital

Seoul, 06591, South Korea

Location

National Taiwan University Hospital

Hsinchu, 300, Taiwan

Location

Kaohsiung Medical University Hospital

Kaohsiung City, 807, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 407219, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Mycobacterium Infections, Nontuberculous; Bronchiectasis; Mycobacterium avium-intracellulare Infection; Respiratory Tract Infections; Mycobacterium Infections; Infections; Respiratory Tract Diseases; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Lung Diseases

Condition Hierarchy (Ancestors)

Bronchial Diseases

Study Officials

• Wassim Fares, MD

  Mannkind Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: During Part A of the study, the identity of the treatments will be concealed by the use of a placebo, and treatment unblinding will only occur in the case of participant emergencies or if requested by the Data and Safety Monitoring Board (DSMB). 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: At least 234 eligible participants will be randomized in a 2:1 ratio of 1 of 2 possible treatment assignments in order to ensure that a minimum of 180 participants are evaluable for efficacy: Clofazimine Inhalation Suspension (N=120) and placebo (n=60). Randomization will be stratified by type of nontuberculous mycobacteria (NTM) infection (Mycobacterium avium complex \[MAC\] infection only vs MAC co-infection with Mycobacterium abscessus complex \[MABSC\] or other NTM species) based on historical samples used to establish eligibility during screening. Enrollment of participants with MAC coinfection with MABSC or other NTM species will be capped at 20% of all participants to limit heterogeneity in the participant population.

Study Record Dates

• First Submitted: May 8, 2024
• First Posted: May 17, 2024
• Study Start: September 11, 2024
• Primary Completion: November 10, 2025
• Study Completion: November 10, 2025
• Last Updated: November 12, 2025

Record last verified: 2025-11

Locations

JP (25); US (54); AU (9); KR (6); TW (5)