TERMINATED

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

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Conditions

MAC Lung DiseaseTreatment Refractory MAC Lung DiseaseMycobacterium Infections, NontuberculousBronchiectasisNTM (Nontuberculous mycobacteria)MAC (Mycobacterium avium complex)MABSC (Mycobacterium abscessus complex)Pulmonary Nontuberculous MycobacteriaRespiratory Infectionantimycobacterial activityantimycobacterial therapyMAC infectionsMAC pulmonary infectionMycobacteriamycobacteriumMycobacterium Avium Complex InfectionsMycobacterium avium complex lung diseasemycobacterium InfectionsNontuberculousNon-tuberculous mycobacterial (NTM) infectionsNontuberculous mycobacterial lung diseaseNon-tuberculous mycobacterial pulmonary diseaseNTM infectionNTM lung diseaseNTM Pulmonary DiseaseNTM lung infectionPulmonary MAC diseasePulmonary Mycobacterium Avium Complex diseaseTreatment refractory mycobacterial lung diseaseTreatment refractory NTM lung infectionTreatment refractory NTM pulmonary diseaseRespiratory Tract diseasesActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsMycobacterium avium-intracellulare InfectionLung diseasesAnti-Bacterial AgentsAnti-infective AgentsAntitubercular AgentsAzithromycinAmikacinEthambutolClofazimineLamprene

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

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

Quick Facts

Study Start:2024-09-11
Study Completion:2025-11-10
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:TERMINATED

Study ID

NCT06418711

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 85 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. 1. Evidence of signed and dated informed consent document(s) indicating the participant has been informed of all pertinent aspects of the trial.
  2. 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. 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. 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. 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. 6. FEV1 ≥40% of predicted during screening, as calculated by the local spirometry laboratory standards.
  7. 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. 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. 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. 10. Willingness and ability to comply with scheduled visits, drug inhalation plan, study procedures, laboratory tests, and study restrictions.
  1. 1. Cystic fibrosis.
  2. 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. 3. Disseminated MAC or MABSC infection or participants with isolated MABSC infection.
  4. 4. Recent (i.e., within the last 3 months from date of screening) ICU admission with or without mechanical ventilation.
  5. 5. Inability to inhale with a nebulizer, in the opinion of the investigator.
  6. 6. Participants with known hypersensitivity to any of the ingredients or excipients of clofazimine.
  7. 7. Prior therapy with clofazimine in the previous 4 months from date of screening.
  8. 8. Participants with known resistance to clofazimine as treatment for MAC (i.e., MIC \>8 ug/mL for MAC).
  9. 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. 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. 11. Current (or planned during the study) pregnancy or breastfeeding.
  12. 12. QT prolongation during screening (450 ms or longer), and/or uncontrolled sinus rhythm (\>110/minute).
  13. 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. 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. 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. 16. Chronic and clinically meaningful, in the opinion of the investigator, abnormalities in potassium, magnesium, or calcium levels.
  17. 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. 18. Current alcohol, medication, or illicit drug abuse.
  19. 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. 20. Any prior use of bedaquiline within 1 year of screening.
  21. 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. 22. Absolute neutrophil count \<500/µL during screening.
  23. 23. Use of prednisone ≥10mg/day within 3 months prior to screening, or other significant immunosuppression as deemed by the investigator.
  24. 24. Estimated glomerular filtration rate \<30mL/minute/1.73 m2 (according to the CKD-EPI 2021 creatine equation) during screening.
  25. 25. Advanced liver disease (Child-Pugh Class A, B, or C).

Contacts and Locations

Principal Investigator

Wassim Fares, MD
STUDY_DIRECTOR
Mannkind Corporation

Study Locations (Sites)

University of Alabama at Birmingham School of Medicine
Birmingham, Alabama, 35294
United States
University of California San Francisco Fresno
Fresno, California, 93701
United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048
United States
Hoag Hospital
Newport Beach, California, 92663
United States
University of California Davis Medical Center
Sacramento, California, 95817
United States
University of California San Francisco
San Francisco, California, 94143
United States
Santa Barbara Cottage Hospital
Santa Barbara, California, 93105
United States
Stanford University
Stanford, California, 94305
United States
National Jewish Health
Denver, Colorado, 80206
United States
UCONN Health
Farmington, Connecticut, 06030-1225
United States
Yale University
New Haven, Connecticut, 06520-8057
United States
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
United States
The George Washington University Medical Faculty Associates
Washington D.C., District of Columbia, 20037
United States
VA Bay Pines
Bay Pines, Florida, 33744
United States
St. Francis Sleep, Allergy & Lung Institute
Clearwater, Florida, 33765
United States
Malcolm Randall Veterans Affairs Medical Center
Gainesville, Florida, 32608
United States
University of Florida College of Medicine
Jacksonville, Florida, 32209
United States
Theia Clinical Research
St. Petersburg, Florida, 33707
United States
University of South Florida
Tampa, Florida, 33620
United States
Midway Specialty Care Center
West Palm Beach, Florida, 33401
United States
Cleveland Clinic
Weston, Florida, 33331
United States
Flourish Research
Winter Park, Florida, 32789
United States
Emory University School Of Medicine
Atlanta, Georgia, 30342
United States
Medster Research
Valdosta, Georgia, 31605
United States
University of Hawaii
Honolulu, Hawaii, 96813
United States
University of Iowa Hospital and Clinics
Iowa City, Iowa, 52242
United States
University of Kansas Medical Center
Kansas City, Kansas, 66160
United States
Infectious Disease Consultants Clinical Research
Wichita, Kansas, 67211
United States
Ochsner Clinic Foundation
New Orleans, Louisiana, 70115
United States
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21287
United States
Massachusetts General Hospital
Boston, Massachusetts, 02114
United States
Henry Ford Hospital
Detroit, Michigan, 48202
United States
Mayo Clinic
Rochester, Minnesota, 55905
United States
University of Missouri
Columbia, Missouri, 65201
United States
Washington University School of Medicine
St Louis, Missouri, 63110
United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198
United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
United States
Rutgers New Jersey Medical School
Newark, New Jersey, 07103
United States
Northwell Health
New Hyde Park, New York, 11042
United States
NYU Langone Health
New York, New York, 10016
United States
Mount Sinai-National Jewish Respiratory Institute
New York, New York, 10029
United States
Columbia University
New York, New York, 10032
United States
NYC Health and Hospitals-Elmhurst
Queens, New York, 11373
United States
Montefiore Medical Center
The Bronx, New York, 10467
United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599-7248
United States
Oregon Health & Science University
Portland, Oregon, 97239
United States
Temple Lung Center
Philadelphia, Pennsylvania, 19140
United States
Reading Hospital
West Reading, Pennsylvania, 19611
United States
AnMed Health
Anderson, South Carolina, 29621
United States
Low Country Infectious Diseases
Charleston, South Carolina, 29414
United States
Medical University of South Carolina
Charleston, South Carolina, 29425
United States
North Texas Infectious Diseases Consultants
Dallas, Texas, 75246
United States
The University of Texas Health Science Center
Tyler, Texas, 75708
United States
UVA Health Infectious Diseases Clinic
Charlottesville, Virginia, 22903
United States

Collaborators and Investigators

Sponsor: Mannkind Corporation

  • Wassim Fares, MD, STUDY_DIRECTOR, Mannkind Corporation

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-09-11
Study Completion Date2025-11-10

Study Record Updates

Study Start Date2024-09-11
Study Completion Date2025-11-10

Terms related to this study

Keywords Provided by Researchers

  • 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

Additional Relevant MeSH Terms

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