Simtuzumab (GS-6624) in the Prevention of Progression of Liver Fibrosis in Subjects With Primary Sclerosing Cholangitis (PSC)

Inclusion Criteria:

- Adult subjects (aged 18-70) with chronic cholestatic liver disease of at least 6
months.

- Liver biopsy consistent with PSC: If a liver biopsy has been performed within 3
months of the screening visit, tissue from that biopsy may be used as the screening
biopsy. Slides would be re-cut from the existing tissue block and submitted for
central reader assessment. Some subjects with PSC may have a normal liver biopsy, in
the event of a normal liver biopsy, the subject must have an abnormal magnetic
resonance cholangiopancreatography (MRCP).

- MRCP consistent with PSC: Some subjects with PSC may have a normal MRCP; in the event
of a normal MRCP, the subject must have an abnormal liver biopsy.

- Exclusion of other causes of liver disease including viral hepatitis ,alcoholic liver
disease,primary biliary cirrhosis and secondary sclerosing cholangitis

- Must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 10 x
the Central Laboratory Upper Limit of Normal (clULN)

- Must have serum creatinine < 2.0 mg/dL

- A negative serum pregnancy test is required for female subjects of childbearing
potential

- All sexually active female subjects of childbearing potential must agree to use a
protocol recommended method of contraception during heterosexual intercourse
throughout the study and for 90 days following the last dose of study medication

- Lactating females must agree to discontinue nursing before starting study treatment

- Male subjects, if not vasectomized, are required to use barrier contraception (condom
plus spermicide) during intercourse from the screening through the study completion
and for 90 days following the last dose of study drug

Exclusion Criteria:

- Pregnant or breast feeding

- Evidence of hepatic decompensation present, including ascites, episodes of hepatic
encephalopathy, variceal bleeding or a prolonged prothrombin time/international
normalized ratio (PT/INR)

- Positive for hepatitis C virus (HCV) RNA

- Positive for HBsAg

- Positive for anti-mitochondrial antibody

- Alcohol consumption greater than 21oz/week for males or 14oz/week for females

- Moderately active ulcerative colitis (UC) defined as either a partial Mayo score of >
4, bleeding score of >1, or current use of oral corticosteroid therapy and/or any
inhibitor of Tumor necrosis factor-α (TNF-α) or α4β7 integrin antagonist

- Positive urine screen for amphetamines, cocaine or opiates (i.e. heroin, morphine) at
screening. Subjects on stable methadone or buprenorphine maintenance treatment for at
least 6 months prior to screening may be included in the study. Subjects with a
positive urine drug screen due to prescription opioid-based medication are eligible
if the prescription and diagnosis are reviewed and approved by the investigator

- Clinically significant cardiac disease

- History of cholangiocarcinoma

- History of other cancers,other than non-melanomatous skin cancer, within 5 years
prior to screening

- Ascending cholangitis within 60 days of screening

- Presence of a percutaneous drain or bile duct stent

- Known hypersensitivity to the investigation product or any of its formulation
excipients

- History of bleeding diathesis within 6 months of screening

- Unavailable for follow-up assessment or concern for subject's compliance with the
protocol procedures;

- Participation in an investigational trial of a drug or device within 30 days prior to
screening

- Major surgical procedure within 30 days prior to screening or the presence of an open
wound