Inclusion Criteria:

• Subjects must be able and willing to provide written informed consent to participate in the study.
• Males and females subjects aged between 18 and 80 years, inclusive, at the time of signing informed consent.
• Verified diagnosis of PSC for at least 3 months prior to Day 1, with or without IBD, based on either a consistent magnetic resonance cholangiogram (MRC) or endoscopic retrograde cholangiogram (ERC) demonstrating bile ducts abnormalities consistent with sclerosing cholangitis. In addition, these subjects will be required to enter the study with a Mayo risk score (Kim et al, 2000) of 0-3, inclusive. For subjects with IBD, documented evidence of IBD either by prior endoscopy or in previous medical records should be ≥ 6 months prior to Day1.
• Serum (ALP) ≥ 1.5 times ULN and with no >20 % fluctuation in the past 3 months.
• In subjects receiving treatment with ursodeoxycholic acid (UDCA), therapy must be stable for at least 3 months prior to Day 1 (no dose adjustment) and at a dose not greater than 20 mg/kg/day so that for subjects who are taking UDCA, the investigational drug can be given as a co-medication.
• Subjects of childbearing potential must agree to use a medically acceptable method of contraceptive to prevent pregnancy in the subject and/or the partner for the duration of their participation in the trial up to 2 months after the last study drug dosing. Medically acceptable methods of contraception that may include: oral contraception or patches (consistently for 3 months prior to trial dosing), Nuva Ring (etonogestrel/ethinyl estradiol vaginal ring), diaphragm with vaginal spermicide, IUD (coil), condom and vaginal spermacide, surgical sterilization (6 month post surgery), post menopausal patient (not experienced a menstrual period for a minimum of 2 years) and progestin implant or injection (used consistently for 3 months prior to dosing).

Exclusion Criteria:

• Presence of documented secondary sclerosing cholangitis (such as ischemic cholangitis, recurrent pancreatitis, intraductal stone disease, surgical or blunt abdominal trauma, recurrent pyogenic cholangitis, choledocholithiasis, toxic sclerosing cholangitis due to chemical agents, or any other cause of secondary sclerosing cholangitis) on prior clinical investigations.
• Small duct PSC.
• Bacterial cholangitis within 30 days prior to the screening visit.
• Presence of percutaneous drain or endoscopic bile duct stent within the last 90 days of the screening visit.
• History of, or suspicion of cholangiocarcinoma by MRC/ERC and other cross sectional imaging , or clinical judgment at screening.
• Prior liver transplantation, or currently listed for liver transplantation on the basis of recurrent cholangitis and with a match-run MELD-Na+ score > 10.
• Presence of other concomitant liver diseases such as primary biliary cholangitis (PBC), autoimmune hepatitis, alcoholic liver disease, confirmed nonalcoholic steatohepatitis (NASH), chronic metabolic liver diseases, e.g. Wilson’s disease, hepatitis B virus surface antigen (HBsAg) positive at screening, detectable serum hepatitis C virus ribonucleic acid (HCV RNA) at screening.
• Cirrhosis and/or hepatic impairment and/or hepatic decompensation including; e.g., ascites, episodes of hepatic encephalopathy or variceal bleeding.
• Subjects with fibrosis evidence of cirrhosis, as determined by local transient elastography (TE; e.g., FibroScan®) values of ≥14.4 kPa (Corpechot et al, 2014), taken within the last 3 months prior to screening. If TE has not been conducted within the 3 months prior to screening then a TE 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 prior to Day 1 requiring intensification of therapy beyond baseline treatment.
• Active Crohn’s disease not currently in remission, as assessed by the investigator and the CRO’s medical monitor.
• Use of oral prednisolone > 10 mg/day and/or hospitalization for IBD within 90 days prior to Day 1 are disallowed.
• AST, ALT, and Total Bilirubin concentrations above the allowed cut-offs, as determined at screening (subjects who show evidence of significant worsening of liver transaminases on repeat measure will be excluded) unless other liver diseases as listed in the Exclusion Criteria can be excluded by biopsy, imaging, or any specific lab results:
  • AST > 200 IU/L males and females;
  • ALT: males > 250 IU/L and females > 200 IU/L;
  • Total Bilirubin > 2.5 mg/dL.
• International normalized ratio (INR) ≥ 1.2.
• Subjects on anticoagulant therapy.
• Platelet count < 150,000/mm3.
• Immunoglobulin G4 (IgG4) > 4 × ULN at screening; or evidence consistent with the diagnosis of IgG4-related sclerosing cholangitis.
• Average weekly alcohol ingestion of ≥ 30g/day for men and ≥ 20 g/day for females.
• Any active malignant disease (within 3 years), other than non-melanomatous skin cancer.
• Human immunodeficiency virus (HIV) infection.
• Existing or intended pregnancy, and/or breast feeding.
• Has received any study medication in the context of another clinical trial within the past the 30 days prior to screening.
• Are taking drug products that are primarily the substrates of CYP2C8, such as chloroquine, paclitaxel, rosiglitazone, repaglinide.
• 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.
  • Note: Cholangitis is a clinical syndrome diagnosed on the basis of features such as fever (≥ 38.2°C), chills or rigors (feeling cold, together with uncontrolled shaking lasting 30 minutes or more), abdominal pain, anorexia/nausea and/or vomiting, pale stools and/or dark urine, and pruritus (itching of the skin) (Chapman et al, 2010; Lindor et al, 2015), occurring as the result of development and/or progression of biliary stricture formation.