Investigation of the Efficacy of Antimycobacterial Therapy on Pulmonary Sarcoidosis Phase II Randomized, Double-blind, Placebo-controlled Trial
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Vanderbilt University
- Enrollment
- 97
- Locations
- 6
- Primary Endpoint
- Change in Percent Predicted Absolute Forced Vital Capacity (FVC) in Participants With Pulmonary Sarcoidosis, Comparing Baseline With Performance After Completion of 16 Weeks of Therapy.
Study Overview
Brief Summary
The primary purpose of this study is to investigate the efficacy and safety of oral antimycobacterial therapy in patients with confirmed progressive pulmonary sarcoidosis. We suspect that the CLEAR regimen will improve the absolute FVC percent predicted in chronic pulmonary sarcoidosis participants.
Detailed Description
Primary Objective: To assess the efficacy and safety of oral CLEAR therapy in patients with confirmed progressive pulmonary sarcoidosis.
Hypothesis
The CLEAR regimen will improve the absolute FVC percent predicted in chronic pulmonary sarcoidosis participants by augmenting T cell responses through the normalization of p56Lck expression and IL-2 production.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with sarcoidosis as defined by the ATS/ERS/WASOG statement on sarcoidosis as defined by the clinical presentation consistent with sarcoidosis, as well as biopsy demonstrating granulomas, and no alternative for the cause of the granulomas, such as tuberculosis for at least one year prior to randomization.
- •Evidence of disease progression as defined by at least one of the following three criteria:
- •Decline of absolute percent predicted of FVC (FVC ≥45% or higher of predicted value) or DLCO of at least 5% on serial measurements (DLCO range >35%, if measured); Radiographic progression in chest imaging on side by side comparison; Change in dyspnea score, as measured by Transition Dyspnea Index (TDI); Positive peripheral immune responses to ESAT-6 as a biomarker of response to CLEAR regimen.
- •Possess evidence of parenchymal or nodal disease on chest radiograph.
Exclusion Criteria
- •Inability to obtain consent
- •Age less than 18 years
- •Female participants of childbearing potential not willing to use one of the following methods of birth control for the duration of the study and 90 days after study completion: condoms, sponge, foams, jellies, diaphragm, non-hormonal intrauterine device, a vasectomized sole partner or abstinence. Note: Oral contraceptive pills are not effective birth control when taking rifamycin. A negative urine pregnancy test at screening visit if female of childbearing potential
- •FVC predicted value is < 45%.
- •End-stage fibrotic pulmonary disease.
- •Significant underlying liver disease.
- •Allergy or intolerance to any of the antibiotics within the CLEAR regimen.
- •Allergy or intolerance to albuterol
- •Poor venous access for obtaining blood samples
- •History of active tuberculosis, close contact with a person with active tuberculosis within the 6 months prior to the screening visit or has a positive PPD.
- •Significant disorder, other than sarcoidosis, that would complicate the treatment evaluation, (such as respiratory, cardiac, neurologic, musculoskeletal or seizure disorders)
- •Use of an investigational drug within 30 days prior to screening or within 5 half-lives of the agent, whichever is longer.
- •Currently receiving >40mg prednisone.
- •ALT or AST >5 times upper limit of normal (ULN)
- •Leukopenia, as defined by WBC <3.0 cells/mm3 or absolute neutrophil count <1000
- •Breast feeding.
- •Color perception impairment as defined by the inability to differentiate colors per personal history or history of optic neuritis from any cause, including from sarcoidosis.
- •If patient is on immunomodulators, they must be on regimen for ≥ 3-month period and on a stable dose for > 4 weeks.
- •Family or personal history of long QT interval
- •Most recent nuclear medicine scan or echocardiogram (if done), demonstrating cardiac ejection fraction <35%
- •Participant has persistent or active infection(s) requiring hospitalization or treatment with antibiotics, antiretrovirals, or antifungals within 30 days prior to baseline. Minocycline and doxycycline are not considered antibiotics when used to treat sarcoidosis.
- •Any significant finding in the patient's medical history or physical or psychiatric exam prior to or after randomization that, in the opinion of the investigator, would affect patient safety or compliance or ability to deliver the study drug according to protocol.
- •On medications that interact with the antibiotics of the CLEAR regimen
- •History of or receiving treatment for pulmonary hypertension. Receiving biologic medication within the 6 months prior to screening visit
Arms & Interventions
Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin
Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD
Intervention: Levofloxacin (Drug)
Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin
Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD
Intervention: Ethambutol (Drug)
Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin
Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD
Intervention: Azithromycin (Drug)
Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin
Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD
Intervention: Rifampin (Drug)
Placebo
Riboflavin will be used for rifampin; encapsulated microcrystalline cellulose will be used to replace the levofloxacin, ethambutol and azithromycin.
The pill count will be the same as the comparator regimen.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Change in Percent Predicted Absolute Forced Vital Capacity (FVC) in Participants With Pulmonary Sarcoidosis, Comparing Baseline With Performance After Completion of 16 Weeks of Therapy.
Time Frame: Baseline to 16 weeks
Change in percent predicted absolute forced vital capacity (FVC) in participants with pulmonary sarcoidosis, comparing baseline with performance after completion of 16 weeks of therapy. This will involve comparing sarcoidosis and placebo after 16 weeks of therapy.
Secondary Outcomes
- FEV1%(Baseline, 4, 8, and 16 and 24 weeks)
- Failure of Standard Therapy(Baseline to 16 weeks)
- Change in Oxygen Saturation(Baseline, 4, 8, and 16 and 24 weeks)
- Fatigue Assessment Scale (FAS).(Baseline, 4, 8, 16 and 24 weeks)
- Adverse Events(24 weeks)
- Change in Level of Dyspnea(Baseline, 4, 8 and 16 weeks)
- Change in the King's Sarcoidosis Questionnaire (KSQ) for the Assessment of Health Status;(Baseline and 16 weeks)
- Abnormal Lab Values(baseline to 16 weeks)
- Radiographic Improvement in Sarcoidosis Lung Disease by Frontal Chest X-ray .(Baseline and 16 weeks)
- Six Minute Walk, Distance in Meters(Baseline, 4, 8, and 16 and 24 weeks)
- Change in the Saint George's Respiratory Questionnaire (SGRQ)(Baseline and 16 weeks)
Investigators
Wonder Drake
Associate Professor of Medicine
Vanderbilt University