Trials
Search / Trial NCT06418711

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

Launched by MANNKIND CORPORATION · May 13, 2024

Trial Information

Current as of February 19, 2025

Recruiting

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

ClinConnect Summary

This clinical trial, called the ICoN-1 Phase 3 Study, is looking at the effectiveness and safety of a new treatment called Clofazimine Inhalation Suspension for patients with MAC lung disease, which is a type of lung infection caused by non-tuberculous mycobacteria. The study will compare this inhaled treatment with a placebo (a treatment that has no active ingredients) when added to the standard care that patients are already receiving. The trial is currently recruiting participants aged 18 to 85 who have been diagnosed with MAC lung disease and have been on a specific treatment regimen for at least six months.

If you are interested in participating, you will need to provide written consent and meet certain criteria, such as being able to produce a sample of sputum (mucus from the lungs) for testing. You will also undergo regular visits to monitor your health and the effects of the treatment. Participants should be aware that there are some exclusions based on other health conditions or recent treatments. This trial aims to determine if adding Clofazimine to existing treatments can help improve lung health and manage the symptoms of MAC lung disease.

Gender

ALL

Eligibility criteria

  • 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).

Trial Officials

Wassim Fares, MD

Study Director

Mannkind Corporation

About Mannkind Corporation

MannKind Corporation is a biopharmaceutical company focused on the development and commercialization of innovative therapies for diabetes and other endocrine-related conditions. With a commitment to advancing patient care, MannKind leverages its proprietary Technosphere® Technology to create inhalable insulin products that enhance the treatment experience for individuals with diabetes. The company aims to address unmet medical needs through rigorous research and clinical trials, striving to improve the quality of life for patients while maintaining the highest standards of safety and efficacy in its product offerings.

Locations

Kansas City, Kansas, United States

Boston, Massachusetts, United States

New York, New York, United States

Bronx, New York, United States

Saint Louis, Missouri, United States

Sacramento, California, United States

Detroit, Michigan, United States

Los Angeles, California, United States

Lebanon, New Hampshire, United States

Anderson, South Carolina, United States

Omaha, Nebraska, United States

Portland, Oregon, United States

Washington, District Of Columbia, United States

West Reading, Pennsylvania, United States

Iowa City, Iowa, United States

Santa Barbara, California, United States

Philadelphia, Pennsylvania, United States

Birmingham, Alabama, United States

Washington, District Of Columbia, United States

New Orleans, Louisiana, United States

Jacksonville, Florida, United States

Columbia, Missouri, United States

New York, New York, United States

Newark, New Jersey, United States

Dallas, Texas, United States

Clearwater, Florida, United States

New Hyde Park, New York, United States

Gainesville, Florida, United States

West Palm Beach, Florida, United States

Valdosta, Georgia, United States

Winter Park, Florida, United States

Charleston, South Carolina, United States

Saint Petersburg, Florida, United States

Sebastian, Florida, United States

Wichita, Kansas, United States

Queens, New York, United States

Charlottesville, Virginia, United States

Fresno, California, United States

Bay Pines, Florida, United States

New York, New York, United States

Tyler, Texas, United States

People applied

Timeline

First submit

Trial launched

Trial updated

Estimated completion

Not reported

Discussion 0