Vancomycin for Primary Sclerosing Cholangitis

A. Determine if OV normalizes serum ALP in adults with PSC. Levels of serum ALP obtained at
6,12,and 18 months of OV treatment, and at 3, and 6 months post OV treatment will be compared
to those obtained at baseline (month 0), and with values at the same study time points in the
placebo arm.

B. Determine if OV stabilizes or improves liver fibrosis assessed by LSM using TE. Liver
stiffness will be measured at 6, 12, and 18 months of OV treatment, and at 6 months post OV
treatment, and values will be compared to those obtained at baseline (month 0), and with
values in the placebo arm.

C. Determine the changes in the intestinal microbiota in relation to the use of OV, and study
the correlation between the changes in the intestinal microbiota and the changes in: 1) liver
enzymes, particularly serum ALP, and 2) liver stiffness, assessed by LSM using TE.

D. Determine if changes in proinflammatory cytokines (TGF-β, IL-4, IL-13, IL-10, etc.)
predict response to OV. Cytokines will be measured at baseline, months 6, 12, 18, and at 3,
and 6 months post OV treatment, if the study is positive.

Inclusion Criteria:

1. Male or female subject age 18-75 years

2. Diagnosis of PSC consistent with the guidelines published by the American Association
for the Study of Liver Diseases (AASLD). All subjects must have an elevated serum ALP
of at least 1.5 times upper limit of normal at baseline plus cholangiographic evidence
of PSC, as demonstrated by magnetic resonance imaging, endoscopic retrograde
cholangiography, direct cholangiography or liver biopsy.

3. An ultrasound (or equivalent imaging modality) that excludes biliary obstruction and
malignancy within 6 months of study entry.

4. If a patient is on any of the following medications and/or supplements, he or she is
expected to remain on the same daily dose through the treatment period: UDCA,
azathioprine, prednisone (or an equivalent steroid compound), methotrexate, a
5-aminosalicylic acid, biologic therapy, and/or a probiotic.

5. PSC with or without inflammatory bowel disease, such as ulcerative colitis or Crohn's
disease.

6. Must agree to comply with the study protocol and provide informed consent.

Exclusion Criteria:

1. Administration of an antibiotic within 3 months prior to the study 2. Pregnancy or
attempting to become pregnant or breastfeeding 3. Presence of any of the following:

1. Hepatitis B infection

2. Hepatitis C infection (antibody positive); patients with a history of hepatitis C
infection will be eligible for this study if they have undetectable levels of HCV RNA

3. Other cholestatic liver diseases such as primary biliary cholangitis and cholestatic
diseases of pregnancy

4. Metabolic liver diseases such as Wilson's disease and hemochromatosis

5. Inherited diseases of the liver such as α-1 antitrypsin deficiency

6. Immunoglobulin G4-related cholangitis

7. PSC with concomitant autoimmune hepatitis (AIH) &/or primary biliary cholangitis
(previously known as primary biliary cirrhosis)

8. Secondary sclerosing cholangitis (SSC)

9. Active acute ascending cholangitis requiring antibiotics

10. CCA (malignant biliary stricture, neoplasm, & cytology/histopathology or positive
fluorescence in situ hybridization (FISH) consistent with adenocarcinoma of the bile
duct)

11. A liver biopsy, if one has been previously obtained, which showed non-alcoholic
steatohepatitis (NASH). Patients with suspected fatty liver imaging will not be
excluded

12. Presence of complications of advanced PSC such as hepatic encephalopathy, portal
hypertension, hepato-renal syndrome and hepato-pulmonary syndrome

13. History of liver transplantation, anticipated need for liver transplantation within 12
months from randomization, or a Model of End Stage Liver Disease (MELD) score of ≥15

14. Ongoing alcohol abuse (>4 drinks per day for men, and >2 drinks per day for women)

15. History of allergic reaction to vancomycin

16. Moderate-to-severe renal impairment with a calculated creatinine clearance of
<60mL/min

r. HIV/AIDS q. Any other conditions or abnormalities that, in that opinion of the
investigator, may compromise the safety of the subject or interfere with the subject
participating in or completing the study