Clofazimine in the Treatment of Pulmonary Mycobacterium Avium Complex (MAC)
Primary Purpose
Mycobacterium Avium Complex
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Clofazimine
sugar pill
Sponsored by
About this trial
This is an interventional treatment trial for Mycobacterium Avium Complex focused on measuring Mycobacterium avium Complex, Clofazimine
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
Sites / Locations
- National Jewish Health
- Georgetown University
- University of South FloridaRecruiting
- University of Chicago
- Louisiana State UniversityRecruiting
- National Heart, Lung and Blood Institute
- Oregon Health & Science UniversityRecruiting
- Temple University Hospital
- University of Texas Health Science CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
clofazimine
sugar pill
Arm Description
Participants receive lamprene
Participants receive placebo
Outcomes
Primary Outcome Measures
Change from Baseline sputum culture 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.
Secondary Outcome Measures
Change from Baseline 6 Minute Walk Test at 24 weeks
Walking distance achieved in 6 minutes is assessed
Change from Baseline PROMIS Fatigue 7a short form questionnaire 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
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
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
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
Mean change in pulmonary function parameters as measured by %predicted FEV1 and FVC
Change from Baseline Erythrocyte Sedimentation Rate at 24 weeks
Detecting change in Inflammatory markers
Change from Baseline C-Reactive Protein levels at 24 weeks
Detecting change in Inflammatory markers
Number of Adverse Events
Comparison of experienced adverse events between the two study groups
Change from Baseline QT interval 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
Detecting changes in liver ALT and AST levels
Change from Baseline complete blood count at week 24
Detecting changes in complete blood count
Change from Baseline Minimal Inhibitory Concentration of MAC isolates in vitro at week 24
Detecting change in MAC isolates sensitivity to clofazimine
Full Information
NCT ID
NCT02968212
First Posted
November 10, 2016
Last Updated
September 29, 2023
Sponsor
Oregon Health and Science University
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, Temple University, University of South Florida
1. Study Identification
Unique Protocol Identification Number
NCT02968212
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 11, 2017 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oregon Health and Science University
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, Temple University, University of South Florida
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mycobacterium Avium Complex
Keywords
Mycobacterium avium Complex, Clofazimine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
102 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
clofazimine
Arm Type
Experimental
Arm Description
Participants receive lamprene
Arm Title
sugar pill
Arm Type
Placebo Comparator
Arm Description
Participants receive placebo
Intervention Type
Drug
Intervention Name(s)
Clofazimine
Other Intervention Name(s)
Lamprene
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
sugar pill
Other Intervention Name(s)
placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change from Baseline sputum culture at 24 weeks
Description
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.
Time Frame
Sputum examined for culture change from Baseline at 24 weeks
Secondary Outcome Measure Information:
Title
Change from Baseline 6 Minute Walk Test at 24 weeks
Description
Walking distance achieved in 6 minutes is assessed
Time Frame
6 Minute Walk Test results examined for change from Baseline at 24 weeks
Title
Change from Baseline PROMIS Fatigue 7a short form questionnaire at 24 weeks
Description
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.
Time Frame
PROMIS Fatigue 7a short form results examined for change from Baseline at 24 weeks
Title
Change from Baseline Quality of Life-Bronchiectasis (QOL-B) with NTM module at 24 weeks
Description
Self-administered questionnaire measuring 8 separate domains: Physical Functioning, Role Functioning, Vitality, Emotional Functioning, Social Functioning, Treatment Burden, Health Perceptions, and Respiratory Symptoms.
Time Frame
QOL-B results examined for change from Baseline at 24 weeks
Title
Change from Baseline CT scan at 24 weeks
Description
CT scans will be computationally evaluated using custom software to provide volumetric assessment of NTM-associated abnormalities.
Time Frame
CT scan examined for change from Baseline at 24 weeks
Title
Change from Baseline semi-quantitative sputum acid fast smear culture at 24 weeks
Description
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.
Time Frame
semi-quantitative sputum acid fast smear culture examined for change from Baseline at 24 weeks
Title
Change from Baseline Spirometry at 24 weeks
Description
Mean change in pulmonary function parameters as measured by %predicted FEV1 and FVC
Time Frame
Spirometry with FEV1/FVC ratio examined for change from Baseline at 24 weeks
Title
Change from Baseline Erythrocyte Sedimentation Rate at 24 weeks
Description
Detecting change in Inflammatory markers
Time Frame
Erythrocyte Sedimentation Rate examined for change from Baseline at 24 weeks
Title
Change from Baseline C-Reactive Protein levels at 24 weeks
Description
Detecting change in Inflammatory markers
Time Frame
C-Reactive Protein levels examined for change from Baseline at 24 weeks
Title
Number of Adverse Events
Description
Comparison of experienced adverse events between the two study groups
Time Frame
Number of Patient-reported and Investigator-reported Adverse Events at 24 weeks
Title
Change from Baseline QT interval at 24 weeks
Description
A 12-lead ECG will be conducted, and the QT interval calculated using Fridericia's formula: QTC = QT / RR 1/3
Time Frame
QT interval examined for change from Baseline at 24 weeks
Title
Change from Baseline blood serum chemistry at week 24
Description
Detecting changes in liver ALT and AST levels
Time Frame
blood serum chemistry examined for change from Baseline at 24 weeks
Title
Change from Baseline complete blood count at week 24
Description
Detecting changes in complete blood count
Time Frame
complete blood count examined for change from Baseline at 24 weeks
Title
Change from Baseline Minimal Inhibitory Concentration of MAC isolates in vitro at week 24
Description
Detecting change in MAC isolates sensitivity to clofazimine
Time Frame
Minimal Inhibitory Concentration of MAC isolates in vitro examined for change from Baseline at 24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amanda Brunton, MPH
Phone
503-494-6327
Email
brunton@ohsu.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Haley Miller
Phone
503-346-1548
Email
millehal@ohsu.edu
Facility Information:
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Individual Site Status
Completed
Facility Name
Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Individual Site Status
Withdrawn
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33620
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tatyana Harris, MBA-MHA, DHA
Phone
813-250-2392
Email
trharris1@usf.edu
First Name & Middle Initial & Last Name & Degree
W. Dwight Miller, MD, MS
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Completed
Facility Name
Louisiana State University
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70803
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivia Rohert
Phone
504-568-2248
Email
orohre@lsuhsc.edu
First Name & Middle Initial & Last Name & Degree
Judd Shellito, MD
Facility Name
National Heart, Lung and Blood Institute
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20814
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Naomi Debacker
Phone
503-346-3435
Email
debacken@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Gina Megson, MPH
Phone
(503) 494-2565
Email
megson@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Kevin L Winthrop, MD, MPH
Facility Name
Temple University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Individual Site Status
Withdrawn
Facility Name
University of Texas Health Science Center
City
Tyler
State/Province
Texas
ZIP/Postal Code
75708
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexis Hester, MA
Phone
903-877-7860
Email
alexis.hester@uttyler.edu
First Name & Middle Initial & Last Name & Degree
Pamela J McShane, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Clofazimine in the Treatment of Pulmonary Mycobacterium Avium Complex (MAC)
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