Phase II Investigation of Antimycobacterial Therapy on Progressive, Pulmonary Sarcoidosis
Condition: Sarcoidosis; Antimycobacterial Therapy
MeSH terms: Sarcoidosis, Pulmonary; Sarcoidosis
Intervention: Levofloxacin; Ethambutol; Azithromycin; Rifampin; Placebo
Intervention description: This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
Intervention MeSH terms: Azithromycin; Levofloxacin; Rifampin; Ethambutol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 97.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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.

          2. 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.

          3. Possess evidence of parenchymal or nodal disease on chest radiograph.

        Exclusion Criteria:

          1. Inability to obtain consent

          2. Age less than 18 years

          3. 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

          4. FVC predicted value is < 45%.

          5. End-stage fibrotic pulmonary disease.

          6. Significant underlying liver disease.

          7. Allergy or intolerance to any of the antibiotics within the CLEAR regimen.

          8. Allergy or intolerance to albuterol

          9. Poor venous access for obtaining blood samples

         10. 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.

         11. Significant disorder, other than sarcoidosis, that would complicate the treatment
             evaluation, (such as respiratory, cardiac, neurologic, musculoskeletal or seizure
             disorders)

         12. Use of an investigational drug within 30 days prior to screening or within 5
             half-lives of the agent, whichever is longer.

         13. Currently receiving >40mg prednisone.

         14. ALT or AST >5 times upper limit of normal (ULN)

         15. Leukopenia, as defined by WBC <3.0 cells/mm3 or absolute neutrophil count <1000

         16. Breast feeding.

         17. 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.

         18. If patient is on immunomodulators, they must be on regimen for ≥ 3-month period and on
             a stable dose for > 4 weeks.

         19. Family or personal history of long QT interval

         20. Most recent nuclear medicine scan or echocardiogram (if done), demonstrating cardiac
             ejection fraction <35%

         21. 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.

         22. 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.

         23. On medications that interact with the antibiotics of the CLEAR regimen

         24. History of or receiving treatment for pulmonary hypertension. Receiving biologic
             medication within the 6 months prior to screening visit