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

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.

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