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

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: 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.

Detailed Summary: 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.
Sponsor: Oregon Health and Science University

Current Primary Outcome: 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: Change from Baseline sputum culture at 24 weeks [ Time Frame: Sputum examined for culture change from Baseline at 24 weeks ]

Current Secondary Outcome:

  • 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 St. George Respiratory Questionnaire (SGRQ) at 24 weeks [ Time Frame: SGRQ results examined for change from Baseline at 24 weeks ]
    Self-administered questionnaire assessing health-related quality of life in subjects with chronic pulmonary disease by evaluating 3 health domains: symptoms, activity, and impacts.
  • 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:

  • 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 ]


Information By: Oregon Health and Science University

Dates:
Date Received: November 10, 2016
Date Started: May 2017
Date Completion: July 2020
Last Updated: March 21, 2017
Last Verified: March 2017