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Clofazimine in the Treatment of Pulmonary Mycobacterium Avium Complex (MAC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02968212
Recruitment Status : Recruiting
First Posted : November 18, 2016
Last Update Posted : October 1, 2020
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
National Jewish Health
The University of Texas Health Science Center at Tyler
National Institute of Allergy and Infectious Diseases (NIAID)
University of Chicago
Information provided by (Responsible Party):
Kevin Winthrop, Oregon Health and Science University

Tracking Information
First Submitted Date  ICMJE November 10, 2016
First Posted Date  ICMJE November 18, 2016
Last Update Posted Date October 1, 2020
Actual Study Start Date  ICMJE April 11, 2017
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2017)
Change from Baseline sputum culture at 24 weeks [ Time Frame: Sputum examined for culture change from Baseline at 24 weeks ]
sputum will be processed for acid fast bacilli stain/acid fast bacterial culture. A semi-quantitative assessment will be made by colony count for patients.
Original Primary Outcome Measures  ICMJE
 (submitted: November 16, 2016)
Change from Baseline sputum culture at 24 weeks [ Time Frame: Sputum examined for culture change from Baseline at 24 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2019)
  • Change from Baseline 6 Minute Walk Test at 24 weeks [ Time Frame: 6 Minute Walk Test results examined for change from Baseline at 24 weeks ]
    Walking distance achieved in 6 minutes is assessed
  • Change from Baseline PROMIS Fatigue 7a short form questionnaire at 24 weeks [ Time Frame: PROMIS Fatigue 7a short form results examined for change from Baseline at 24 weeks ]
    Self-administered questionnaire assessing a range of self-reported symptoms over the past seven days, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. Fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities.
  • Change from Baseline Quality of Life-Bronchiectasis (QOL-B) with NTM module at 24 weeks [ Time Frame: QOL-B results examined for change from Baseline at 24 weeks ]
    Self-administered questionnaire measuring 8 separate domains: Physical Functioning, Role Functioning, Vitality, Emotional Functioning, Social Functioning, Treatment Burden, Health Perceptions, and Respiratory Symptoms.
  • Change from Baseline CT scan at 24 weeks [ Time Frame: CT scan examined for change from Baseline at 24 weeks ]
    CT scans will be computationally evaluated using custom software to provide volumetric assessment of NTM-associated abnormalities.
  • Change from Baseline semi-quantitative sputum acid fast smear culture at 24 weeks [ Time Frame: semi-quantitative sputum acid fast smear culture examined for change from Baseline at 24 weeks ]
    sputum will be processed for acid fast bacilli stain/acid fast bacterial culture. A semi-quantitative assessment will be made by colony count for patients.
  • Change from Baseline Spirometry at 24 weeks [ Time Frame: Spirometry with FEV1/FVC ratio examined for change from Baseline at 24 weeks ]
    Mean change in pulmonary function parameters as measured by %predicted FEV1 and FVC
  • Change from Baseline Erythrocyte Sedimentation Rate at 24 weeks [ Time Frame: Erythrocyte Sedimentation Rate examined for change from Baseline at 24 weeks ]
    Detecting change in Inflammatory markers
  • Change from Baseline C-Reactive Protein levels at 24 weeks [ Time Frame: C-Reactive Protein levels examined for change from Baseline at 24 weeks ]
    Detecting change in Inflammatory markers
  • Number of Adverse Events [ Time Frame: Number of Patient-reported and Investigator-reported Adverse Events at 24 weeks ]
    Comparison of experienced adverse events between the two study groups
  • Change from Baseline QT interval at 24 weeks [ Time Frame: QT interval examined for change from Baseline at 24 weeks ]
    A 12-lead ECG will be conducted, and the QT interval calculated using Fridericia's formula: QTC = QT / RR 1/3
  • Change from Baseline blood serum chemistry at week 24 [ Time Frame: blood serum chemistry examined for change from Baseline at 24 weeks ]
    Detecting changes in liver ALT and AST levels
  • Change from Baseline complete blood count at week 24 [ Time Frame: complete blood count examined for change from Baseline at 24 weeks ]
    Detecting changes in complete blood count
  • Change from Baseline Minimal Inhibitory Concentration of MAC isolates in vitro at week 24 [ Time Frame: Minimal Inhibitory Concentration of MAC isolates in vitro examined for change from Baseline at 24 weeks ]
    Detecting change in MAC isolates sensitivity to clofazimine
Original Secondary Outcome Measures  ICMJE
 (submitted: November 16, 2016)
  • Change from Baseline 6 Minute Walk Test at 24 weeks [ Time Frame: 6 Minute Walk Test results examined for change from Baseline at 24 weeks ]
  • Change from Baseline St. George Respiratory Questionnaire (SGRQ) at 24 weeks [ Time Frame: SGRQ results examined for change from Baseline at 24 weeks ]
  • Change from Baseline Quality of Life-Bronchiectasis (QOL-B) with NTM module at 24 weeks [ Time Frame: QOL-B results examined for change from Baseline at 24 weeks ]
  • Change from Baseline CT scan at 24 weeks [ Time Frame: CT scan examined for change from Baseline at 24 weeks ]
  • Change from Baseline semi-quantitative sputum acid fast smear culture at 24 weeks [ Time Frame: semi-quantitative sputum acid fast smear culture examined for change from Baseline at 24 weeks ]
  • Change from Baseline Spirometry at 24 weeks [ Time Frame: Spirometry with FEV1/FVC ratio examined for change from Baseline at 24 weeks ]
  • Change from Baseline Erythrocyte Sedimentation Rate at 24 weeks [ Time Frame: Erythrocyte Sedimentation Rate examined for change from Baseline at 24 weeks ]
  • Change from Baseline High-Sensitivity C-Reactive Protein levels at 24 weeks [ Time Frame: High-Sensitivity C-Reactive Protein levels examined for change from Baseline at 24 weeks ]
  • Number of Adverse Events [ Time Frame: Number of Patient-reported and Investigator-reported Adverse Events at 24 weeks ]
  • Change from Baseline QT interval at 24 weeks [ Time Frame: QT interval examined for change from Baseline at 24 weeks ]
  • Change from Baseline blood serum chemistry at week 24 [ Time Frame: blood serum chemistry examined for change from Baseline at 24 weeks ]
  • Change from Baseline complete blood count at week 24 [ Time Frame: complete blood count examined for change from Baseline at 24 weeks ]
  • Change from Baseline Minimal Inhibitory Concentration of MAC isolates in vitro at week 24 [ Time Frame: Minimal Inhibitory Concentration of MAC isolates in vitro examined for change from Baseline at 24 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clofazimine in the Treatment of Pulmonary Mycobacterium Avium Complex (MAC)
Official Title  ICMJE Phase 2 Study of Clofazimine for the Treatment of Pulmonary Mycobacterium Avium Disease
Brief Summary

The purpose of this study is to evaluate the clinical effectiveness and safety of clofazimine when used to treat Mycobacteria avium complex (MAC) lung disease.

Funding Source - FDA OOPD

Detailed Description Clofazimine is an orphan antibiotic drug that is no longer available through pharmacies in the United States. It is approved for the treatment of Mycobacterium leprae (leprosy) infections. Clofazimine has been used for many years off-label against other Mycobacterium, including Mycobacteria avium complex (MAC) lung disease, an increasingly prevalent infection in older Americans. The U.S. Food and Drug Administration currently oversees clofazimine use to treat MAC lung disease through a special investigational drug access program. However, to date, there is little understanding of the benefits and risks of clofazimine when used to treat MAC lung disease. Accordingly, the investigators have developed a randomized, placebo-controlled clinical trial to assess the clinical efficacy and safety of clofazimine. To be eligible, participants must have MAC lung disease, positive sputum cultures for MAC, and not currently taking antibiotics for MAC. Eligible participants (102 total enrolled) will be randomly given either clofazimine or placebo for 6 months, and followed closely by their treating physician. The percentage of participants who become culture negative in each group will be compared, as it is suspected that participants treated with clofazimine will be more likely to become culture negative. The safety of clofazimine will be measured as well as other potential benefits of the therapy including changes in lung function and quality of life.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Mycobacterium Avium Complex
Intervention  ICMJE
  • Drug: Clofazimine
    All participants in the experimental/treatment arm on this protocol will take a loading dose of 200 mg daily in soft capsule form of clofazimine for 16 weeks, dropping to 100 mg daily for the next 8 weeks.
    Other Name: Lamprene
  • Other: sugar pill
    All participants in the placebo arm on this protocol will take placebo in soft capsule form daily dropping to a smaller dose after 16 weeks to mirror the treatment arm dosing.
    Other Name: placebo
Study Arms  ICMJE
  • Experimental: clofazimine
    Participants receive lamprene
    Intervention: Drug: Clofazimine
  • Placebo Comparator: sugar pill
    Participants receive placebo
    Intervention: Other: sugar pill
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 16, 2016)
102
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2022
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • At least 2 positive MAC sputum cultures in the last 12 months with at least one obtained within 12 weeks prior to randomization
  • Meet ATS/IDSA 2007 pulmonary disease criteria
  • Adult males and females age 18 or over
  • Ability to provide informed consent for the use of study drug

Exclusion Criteria:

  • Any patient who is unwilling or unable to provide consent or to comply with this protocol
  • Cavitary NTM disease
  • Patients who are currently taking or within the prior 12 weeks received any of the following: bedaquiline, or any component of ATS/IDSA multi-drug recommended therapy (macrolide, ethambutol, rifampin) for MAC
  • Current usage of inhaled amikacin, tobramycin, or gentamicin
  • In the judgment of the investigator, the patient is not a candidate for observation (e.g. severe symptoms, extensive disease burden) but rather should be treated with standard multi-drug therapy
  • Prior use of clofazimine that has resulted in an allergy to clofazimine or a severe adverse reaction
  • Current usage of medications associated with QT prolongation (see Appendix C for full list of prohibited concomitant medications)
  • Corrected QT (QTc) interval on electrocardiogram (ECG) > 470 ms for females or 450 ms for males, calculated using Fridericia's formula60,61
  • Advanced lung disease (FEV<30%)
  • HIV
  • Active pulmonary tuberculosis requiring treatment at screening
  • Active pulmonary malignancy or chemotherapy or radiation within 1 year of screening
  • Use of chronic systemic corticosteroids at doses of 15 mg/day for more than 12 weeks
  • Prior lung or other solid organ transplant
  • Pregnancy, or breastfeeding that will continue during treatment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Peter Sullivan 503-494-8022 sullivpe@ohsu.edu
Contact: Megan Wardrop, MS 503-346-3752 wardrop@ohsu.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02968212
Other Study ID Numbers  ICMJE FD-R-5401
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Kevin Winthrop, Oregon Health and Science University
Study Sponsor  ICMJE Oregon Health and Science University
Collaborators  ICMJE
  • National Heart, Lung, and Blood Institute (NHLBI)
  • National Jewish Health
  • The University of Texas Health Science Center at Tyler
  • National Institute of Allergy and Infectious Diseases (NIAID)
  • University of Chicago
Investigators  ICMJE Not Provided
PRS Account Oregon Health and Science University
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP