Inclusion Criteria:

• Subjects with chronic cholestatic liver disease for at least 6 months
• Clinical diagnosis of PSC as evident by chronic cholestasis of more than six months duration with either a consistent magnetic resonance cholangiopancreatography (MRCP)/endoscopic retrograde cholangiopancreatography (ERCP) showing sclerosing cholangitis, or a liver biopsy taken at any time consistent with PSC in the absence of a documented alternative etiology for sclerosing cholangitis. If diagnosis of PSC was made by histology alone, it must require the presence of fibro-obliterative lesions (ie, onion skin lesions)
• Documented evidence of Inflammatory Bowel Disease (IBD) either by prior endoscopy or in previous medical records, for >= 6 months. In addition, subjects will be required to enter the study with a Partial Mayo Risk score of 0-3, inclusively
• In subjects receiving treatment with ursodeoxycholic acid (UDCA), therapy must be stable for at least 3 months, and at a dose not greater than 20 mg/kg/day
• Serum ALP greater than 1.5 × upper limit of normal (ULN)
• Ability to understand and sign a written informed consent form (ICF)
• Subjects receiving allowed concomitant medications need to be on stable therapy for 28 days prior to the Baseline Visit

Exclusion Criteria:

• Presence of documented secondary sclerosing cholangitis (such as ischemic cholangitis, recurrent pancreatitis, intraductal stone disease, severe bacterial cholangitis, surgical or blunt abdominal trauma, recurrent pyogenic cholangitis, choledocholithiasis, toxic slerosing cholangitis due to chemical agents, or any other cause of secondary sclerosing cholangitis) on prior clinical investigations
• Small duct PSC
• Presence of percutaneous drain or bile duct stent
• History of cholangiocarcinoma or high clinical suspicion over dominant stricture within 1 year by MRCP/ERCP or clinical judgment
• Ascending cholangitis within 60 days prior to Screening
• Alcohol consumption greater than 21 units/week for males or 14 units/week for females (one unit of alcohol is ½ pint of beer [285 mL], 1 glass of spirits [25 mL] or 1 glass of wine [125 mL])
• Prior or planned liver transplantation
• Presence of alternative causes of chronic liver disease, including alcoholic liver disease, nonalcoholic steatohepatitis, primary biliary cirrhosis, autoimmune hepatitis
• History of cirrhosis and/or hepatic impairment (Child-Pugh classes A, B and C) and/or hepatic decompensation including ascites, encephalopathy or variceal bleeding. Subjects who show evidence of significant worsening of hepatic function will be excluded
• Subjects with fibrosis evidence of cirrhosis, as determined by local transient elastography (TE, e.g., Fibroscan) values of >= 13.0 kPa, taken within the last 6 months. If TE has not been conducted within the 6 months prior to screening then one will be conducted during the screening period and can be used as the Baseline value.
• Moderate to Severe active IBD or flare in colitis activity within the last 90 days requiring intensification of therapy beyond Baseline treatment. Subjects with stable mild to moderate IBD, who are on treatment, are allowed provided they are stable for 3 months with 5-amino salicylic acid drugs or Azathioprine (allowed dose of azathioprine is 50-200 mg/day)
• Use of oral prednisolone > 10 mg/day, biologics and/or hospitalization for colitis within 90 days are disallowed
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT); above the allowed cut-offs, as determined by the mean Screening and pre-Baseline values (subjects who show evidence of significant worsening of liver transaminases on repeat measure will be excluded):
  • AST > 200 IU/L males and females
  • ALT: males > 250 IU/L and females > 200 IU/L
• Total Bilirubin and Direct Bilirubin; above the allowed cut-offs, as determined by the mean Screening and pre-Baseline values (subjects who show evidence of significant worsening of bilirubin will be excluded):
  • Total Bilirubin ≥ 1.5 mg/dL
  • Direct Bilirubin ≥ 0.5 mg/dL
• International normalized ratio > 1.3 in the absence of anticoagulants
• Immunoglobulin G4 (IgG4) > 4 × ULN at Screening or evidence of IgG4-related sclerosing cholangitiss
• Females who are pregnant or breastfeeding
• Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing and protocol requirements