Clinical trial NCT02968212: Clofazimine in the Treatment of Pulmonary Mycobacterium Avium Complex (MAC)
Official title: Phase 2 Study of Clofazimine for the Treatment of Pulmonary Mycobacterium Avium Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Mycobacterium Avium Complex
Keywords: Mycobacterium avium Complex
Clofazimine
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Jewish Health
name: The University of Texas Health Science Center at Tyler
name: National Institute of Allergy and Infectious Diseases (NIAID)
name: University of Chicago
name: Temple University
name: University of South Florida
First posted: 2016-11-18
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from Baseline sputum culture at 24 weeks
timeFrame: Sputum examined for culture change from Baseline at 24 weeks
Secondary outcomes:
measure: Change from Baseline 6 Minute Walk Test at 24 weeks
timeFrame: 6 Minute Walk Test results examined for change from Baseline at 24 weeks
measure: Change from Baseline PROMIS Fatigue 7a short form questionnaire at 24 weeks
timeFrame: PROMIS Fatigue 7a short form results examined for change from Baseline at 24 weeks
measure: Change from Baseline Quality of Life-Bronchiectasis (QOL-B) with NTM module at 24 weeks
timeFrame: QOL-B results examined for change from Baseline at 24 weeks
measure: Change from Baseline CT scan at 24 weeks
timeFrame: CT scan examined for change from Baseline at 24 weeks
measure: Change from Baseline semi-quantitative sputum acid fast smear culture at 24 weeks
timeFrame: semi-quantitative sputum acid fast smear culture examined for change from Baseline at 24 weeks
measure: Change from Baseline Spirometry at 24 weeks
timeFrame: Spirometry with FEV1/FVC ratio examined for change from Baseline at 24 weeks
measure: Change from Baseline Erythrocyte Sedimentation Rate at 24 weeks
timeFrame: Erythrocyte Sedimentation Rate examined for change from Baseline at 24 weeks
measure: Change from Baseline C-Reactive Protein levels at 24 weeks
timeFrame: C-Reactive Protein levels examined for change from Baseline at 24 weeks
measure: Number of Adverse Events
timeFrame: Number of Patient-reported and Investigator-reported Adverse Events at 24 weeks
measure: Change from Baseline QT interval at 24 weeks
timeFrame: QT interval examined for change from Baseline at 24 weeks
measure: Change from Baseline blood serum chemistry at week 24
timeFrame: blood serum chemistry examined for change from Baseline at 24 weeks
measure: Change from Baseline complete blood count at week 24
timeFrame: complete blood count examined for change from Baseline at 24 weeks
measure: Change from Baseline Minimal Inhibitory Concentration of MAC isolates in vitro at week 24
timeFrame: Minimal Inhibitory Concentration of MAC isolates in vitro examined for change from Baseline at 24 weeks
Other outcomes:
Locations:
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baton Rouge
country: United States
facility: Louisiana State University
state: Louisiana
city: Bethesda
country: United States
facility: National Heart, Lung and Blood Institute
state: Maryland
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Tyler
country: United States
facility: University of Texas Health Science Center
state: Texas
Study officials:
affiliation: Oregon Health and Science University
name: Kevin Winthrop, MD
role: PRINCIPAL_INVESTIGATOR
References: