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MAC Lung DiseasePhase 3ICoN-1NCT06418711

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

A Phase 3 study testing Clofazimine Inhalation Suspension in people with MAC Lung Disease and Treatment Refractory MAC Lung Disease, run by Mannkind Corporation at 99 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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) Read more about this study

Who is it for?
Ages 18 to 85 years
What is being tested?
Clofazimine Inhalation Suspension
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
132 participants
Where
99 sitesin 5 countries
Study dates
11 Sep 2024to 10 Nov 2025
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 10Show fewer
  • 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.

Who cannot join

  • 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.
Show all 25Show fewer
  • 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.
  • Chronic and clinically meaningful, in the opinion of the investigator, abnormalities in potassium, magnesium, or calcium levels.
  • 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.
  • Current alcohol, medication, or illicit drug abuse.
  • 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.
  • Any prior use of bedaquiline within 1 year of screening.
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 times upper limit of normal (ULN) or total bilirubin >1.5 times ULN during screening.
  • Absolute neutrophil count <500/µL during screening.
  • Use of prednisone ≥10mg/day within 3 months prior to screening, or other significant immunosuppression as deemed by the investigator.
  • Estimated glomerular filtration rate <30mL/minute/1.73 m2 (according to the CKD-EPI 2021 creatine equation) during screening.
  • Advanced liver disease (Child-Pugh Class A, B, or C).

Trial locations and contacts

99 sites in 5 countries.

99 sites in 5 countries

United States54 sites

  • AnMed Health

    Anderson, South Carolina, 29621

  • Emory University School Of Medicine

    Atlanta, Georgia, 30342

  • Johns Hopkins University School of Medicine

    Baltimore, Maryland, 21287

  • VA Bay Pines

    Bay Pines, Florida, 33744

  • University of Alabama at Birmingham School of Medicine

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599-7248

  • Low Country Infectious Diseases

    Charleston, South Carolina, 29414

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • UVA Health Infectious Diseases Clinic

    Charlottesville, Virginia, 22903

  • St. Francis Sleep, Allergy & Lung Institute

    Clearwater, Florida, 33765

  • University of Missouri

    Columbia, Missouri, 65201

  • North Texas Infectious Diseases Consultants

    Dallas, Texas, 75246

  • National Jewish Health

    Denver, Colorado, 80206

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • UCONN Health

    Farmington, Connecticut, 06030-1225

  • University of California San Francisco Fresno

    Fresno, California, 93701

  • Malcolm Randall Veterans Affairs Medical Center

    Gainesville, Florida, 32608

  • University of Hawaii

    Honolulu, Hawaii, 96813

  • University of Iowa Hospital and Clinics

    Iowa City, Iowa, 52242

  • University of Florida College of Medicine

    Jacksonville, Florida, 32209

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Yale University

    New Haven, Connecticut, 06520-8057

  • Northwell Health

    New Hyde Park, New York, 11042

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70115

  • NYU Langone Health

    New York, New York, 10016

  • Mount Sinai-National Jewish Respiratory Institute

    New York, New York, 10029

  • Columbia University

    New York, New York, 10032

  • Rutgers New Jersey Medical School

    Newark, New Jersey, 07103

  • Hoag Hospital

    Newport Beach, California, 92663

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Temple Lung Center

    Philadelphia, Pennsylvania, 19140

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • NYC Health and Hospitals-Elmhurst

    Queens, New York, 11373

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California Davis Medical Center

    Sacramento, California, 95817

  • University of California San Francisco

    San Francisco, California, 94143

  • Santa Barbara Cottage Hospital

    Santa Barbara, California, 93105

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Theia Clinical Research

    St. Petersburg, Florida, 33707

  • Stanford University

    Stanford, California, 94305

  • University of South Florida

    Tampa, Florida, 33620

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • The University of Texas Health Science Center

    Tyler, Texas, 75708

  • Medster Research

    Valdosta, Georgia, 31605

  • Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • The George Washington University Medical Faculty Associates

    Washington D.C., District of Columbia, 20037

  • Midway Specialty Care Center

    West Palm Beach, Florida, 33401

  • Reading Hospital

    West Reading, Pennsylvania, 19611

  • Cleveland Clinic

    Weston, Florida, 33331

  • Infectious Disease Consultants Clinical Research

    Wichita, Kansas, 67211

  • Flourish Research

    Winter Park, Florida, 32789

Other trials in United States

Japan25 sites

  • Aso Iizuka Hospital

    Fukuoka, 811-3195

  • National Hospital Organization Fukuokahigashi Medical Center

    Fukuoka, 811-3195

  • Fukuoka University Hospital

    Fukuoka, 814-0180

  • Fukuoka University Chikushi Hospital

    Fukuoka, 818-8502

  • National Hospital Organization Omuta National Hospital

    Fukuoka, 837-0911

  • National Hospital Organization Shibukawa Medical Center

    Gunma, 377-0280

  • Himeji Medical Center

    Hyōgo, 670-8520

  • Ibarakihigashi National Hospital

    Ibaraki, 319-1113

  • Kameda Clinic

    Kamogawa-shi, 296-0041

  • SHOWA University Fujigaoka Hospital

    Kanagawa, 227-8501

  • Minami Kyoto Hospital

    Kyoto, 610-0113

  • Matsusaka Municipal Hospital

    Matsusaka, 515-8544

  • Sendai Kousei Hospital

    Miyagi, 980-0873

  • Nishiniigata Chuo Hospital

    Niigata, 945-8585

  • National Hospital Organization - Osaka Toneyama Medical Center

    Osaka, 560-8552

  • Saitama Prefectural Cardiovascular and Respiratory Center

    Saitama, 180-8610

  • National Hospital Organization Kinki-Chuo Chest Medical Center

    Sakai, 591-8555

  • Keio University Hospital

    Shinjuku-ku, 160-8582

  • National Hospital Organization Tenryu Hospital

    Shizuoka, 434-8511

  • Mutual Aid Associations Toranomon Hospital

    Tokyo, 105-8470

  • Toho University Omori Medical Center

    Tokyo, 143-8541

  • Center Hospital of the National Center for Global Health and Medicine

    Tokyo, 162-8655

  • Japanese Red Cross Musashino Hospital

    Tokyo, 180-8610

  • Japan Anti-Tuberculosis Association Fukujuji Hospital

    Tokyo, 204-8522

  • SHOWA University Northern Yokohama Hospital

    Yokohama, 224-8503

Other trials in Japan

Australia9 sites

  • Royal Adelaide Hospital

    Adelaide, 5000

  • Sunshine Coast University Hospital

    Birtinya, Queensland, 4575

  • The Prince Charles Hospital

    Brisbane, Queensland, 4032

  • Concord Repatriation General Hospital

    Concord

  • Monash University Centre for Inflammatory Diseases

    Cranbourne, Victoria, 3977

  • Gallipoli Medical Research Foundation

    Greenslopes, Queensland, 4064

  • Alfred Health

    Melbourne, Victoria, 3004

  • Royal Perth Hospital Respiratory Clinic

    Perth, Western Australia, 6000

  • Macquarie University Clinical Trials Unit

    Sydney, New South Wales, 2109

Other trials in Australia

South Korea6 sites

  • Chonnam National University Hospital

    Gwangju, 61469

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

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

    Seoul, 06591

Other trials in South Korea

Taiwan5 sites

  • National Taiwan University Hospital

    Hsinchu, 300

  • Kaohsiung Medical University Hospital

    Kaohsiung City, 807

  • Taichung Veterans General Hospital

    Taichung, 407219

  • Taipei Veterans General Hospital

    Taipei, 112

  • National Taiwan University Hospital

    Taipei

Other trials in Taiwan

About this study

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

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

Read the 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.

Being tested
Clofazimine Inhalation Suspension, Placebo
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
Medical subject headings
Mycobacterium Infections, Nontuberculous, Bronchiectasis, Mycobacterium avium-intracellulare Infection, Respiratory Tract Infections, Mycobacterium Infections, Infections, Respiratory Tract Diseases, Actinomycetales Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Clofazimine Inhalation SuspensionDrug

    Also called MNKD-101

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

  • PlaceboDrug

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

Study groups in NCT06418711
Study groupRoleWhat they receive
Clofazimine Inhalation SuspensionExperimentalMNKD-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
Receives: Drug: Clofazimine Inhalation Suspension
PlaceboPlacebo comparatorThe 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. (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)

    Measured: Baseline to the end of Month 6

  2. (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)

    Measured: Baseline to end of Month 6

Secondary outcomes (5)

  1. (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)

    Measured: Baseline to the end of Month 6

  2. (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

    Measured: Baseline to the end of Month 6

  3. (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

    Measured: Baseline to the end of Month 6

  4. (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

    Measured: Baseline to the end of Month 6

  5. (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

    Measured: Baseline to the end of Month 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2024
  2. Study start11 Sep 2024
  3. Primary completion10 Nov 2025
  4. Study completion10 Nov 2025

Why it stopped: Futility

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
132 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06418711
Sponsor's protocol ID
MKC-CI-002
Acronym
ICoN-1
Status last verified
Nov 2025
First submitted
8 May 2024
Last updated
12 Nov 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Clofazimine Inhalation Suspension in people with MAC Lung Disease and Treatment Refractory MAC Lung Disease, run by Mannkind Corporation at 99 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 99 sites in United States, Japan, Australia, South Korea, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Futility). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

(Part A) Sputum culture conversion (i.e., 3 consecutive monthly sputum cultures negative for MAC) by the end of Month 6 (time frame: Baseline to the end of Month 6). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06418711.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2025.

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