Phase II Investigation of Antimycobacterial Therapy on Progressive, Pulmonary Sarcoidosis

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.

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