Phase 2 Study of Clofazimine for the Treatment of Pulmonary Mycobacterium Avium Disease
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 102
- 试验地点
- 13
- 主要终点
- Change from Baseline sputum culture at 24 weeks
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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%)
- •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
研究组 & 干预措施
clofazimine
Participants receive lamprene
干预措施: Clofazimine (Drug)
sugar pill
Participants receive placebo
干预措施: sugar pill (Other)
结局指标
主要结局
Change from Baseline sputum culture at 24 weeks
时间窗: 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.
次要结局
- Number of Adverse Events(Number of Patient-reported and Investigator-reported Adverse Events at 24 weeks)
- Change from Baseline 6 Minute Walk Test at 24 weeks(6 Minute Walk Test results examined for change from Baseline at 24 weeks)
- Change from Baseline PROMIS Fatigue 7a short form questionnaire at 24 weeks(PROMIS Fatigue 7a short form results examined for change from Baseline at 24 weeks)
- Change from Baseline Quality of Life-Bronchiectasis (QOL-B) with NTM module at 24 weeks(QOL-B results examined for change from Baseline at 24 weeks)
- Change from Baseline CT scan at 24 weeks(CT scan examined for change from Baseline at 24 weeks)
- Change from Baseline semi-quantitative sputum acid fast smear culture at 24 weeks(semi-quantitative sputum acid fast smear culture examined for change from Baseline at 24 weeks)
- Change from Baseline Spirometry at 24 weeks(Spirometry with FEV1/FVC ratio examined for change from Baseline at 24 weeks)
- Change from Baseline C-Reactive Protein levels at 24 weeks(C-Reactive Protein levels examined for change from Baseline at 24 weeks)
- Change from Baseline QT interval at 24 weeks(QT interval examined for change from Baseline at 24 weeks)
- Change from Baseline Erythrocyte Sedimentation Rate at 24 weeks(Erythrocyte Sedimentation Rate examined for change from Baseline at 24 weeks)
- Change from Baseline blood serum chemistry at week 24(blood serum chemistry examined for change from Baseline at 24 weeks)
- Change from Baseline complete blood count at week 24(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(Minimal Inhibitory Concentration of MAC isolates in vitro examined for change from Baseline at 24 weeks)
研究者
Kevin Winthrop
Professor
Oregon Health and Science University