Clinical Trials

Inclusion Criteria

• Male or female aged 18 to 75 years
• Must provide written informed consent and agree to comply with the trial protocol
• Must have a diagnosis of Primary Sclerosing Cholangitis (based on cholangiography at any point in time)
• Must have had a cholangiography within the past 12 months
• Alkaline phosphatase at screening ≥ 2x ULN
• Total bilirubin at screening < 2.5x ULN
• For subjects with concomitant inflammatory bowel disease
  • Colonoscopy (if subject has a colon) or other appropriate endoscopic procedure within 12 months of Day 0 confirming no dysplasia or colorectal cancer
  • Subjects with Crohn's Disease (CD) must be in remission as defined by a Crohn's Disease Activity Index (CDAI) <150
  • Subjects with ulcerative colitis (UC) must either be in remission or have mild disease
    • Remission is defined as a partial Mayo score of ≤ 2 with no individual sub-score exceeding 1 point
    • Mild disease is defined as a partial Mayo score ≤ 3 with no individual sub-score exceeding 1 point
• For subjects being administered UDCA (ursodeoxycholic acid) as part of their standard of care, the dose must have been stable for ≥ 3 months prior to, and including, Day 0 and must not have exceeded 20 mg/kg/day during this time
• Subjects being administered biologic treatments (eg, anti-tumor necrosis factor (TNF) or anti-integrin monoclonal antibodies), immunosuppressants, systemic corticosteroids, or statins, must have been on a stable dose for ≥ 3 months prior to, and including, Day 0 and should plan to remain on a stable dose throughout the trial
• Female subjects of childbearing potential must use atleast 1 effective method (≤1% failure rate) of contraception during the trial and until 4 weeks following the last dose of IP (including long term safety extension doses)

Exclusion Criteria

• Evidence of a secondary cause of sclerosing cholangitis at screening
• Immunoglobulin G4 (IgG4) > 4x ULN at screening or evidence of IgG4 sclerosing cholangitis
• Small duct cholangitis in the absence of large duct disease
• Presence of clinical complications of chronic liver disease or clinically significant hepatic decompensation, including
  • Current Child Pugh classification B or C
  • History of liver transplantation
  • Current end stage liver disease score ≥ 12
  • History of, current diagnosis of, or suspicion of
    • Cholangiocarcinoma 
    • Other hepatobiliary malignancy
    • Biliary tract dysplasia
    • Cirrhosis with complications
    • Spontaneous bacterial peritonitis
    • Hepatocellular carcinoma 
    • Hepatic encephalopathy (as assessed by the investigator)
    • Portal hypertension with complications, including known
      • Gastric or large esophageal varices
      • Poorly controlled or diuretic resistant ascites
      • History of variceal bleeds
      • Related therapeutic or prophylactic interventions e.g., beta blockers, insertion of variceal bands or transjugular intrahepatic portosystemic shunt
  • Hepatorenal syndrome (type I or II) 
• Screening serum creatinine > 2 mg/dL (178 μmol/L)
• Platelet count < 50 x 10⁹/L
• Clinical evidence of dominant stricture (as evidenced by cholangiography or other appropriate imaging modality within the 12 months prior to Day 0) or current biliary stent
• Current cholecystitis or gallstones (identified by hepatic imaging)
• Colonic dysplasia within ≤ 5 years prior to Day 0
• History of small bowel resection
• History of other chronic liver diseases, including, but not limited to
  • Primary biliary cirrhosis
  • Alcoholic liver disease
  • Non-alcoholic fatty liver disease
  • Autoimmune hepatitis
  • Hepatitis B virus (unless seroconverted and no positive Hepatitis B Virus DNA)
  • Hepatitis C virus and overlap syndrome
• Known Gilbert's syndrome or elevations in unconjugated (indirect) bilirubin >ULN
• Known history of human immunodeficiency virus (HIV) infection
• Currently experiencing, or experienced within ≤ 3 months of screening, pruritus requiring systemic or enteral treatment
• Known or suspected acute cholangitis in the 3 months prior to, and including, day 0 including cholangitis treated with antibiotics
• Administration of antibiotics is prohibited ≤1 month of day 0  unless subject is on a stable prophylaxis dose for at least 3 months prior to day 0
• Administration of the following medications is prohibited ≤ 6 months of day 0 and throughout the trial fenofibrate or other fibrates and potentially hepatotoxic medications including α-methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin
• IBD flare during screening up to and including day 0 where "flare" is defined as follows
  • UC flare: partial Mayo Score ≥ 5
  • CD flare: CDAI ≥ 250
• Evidence of deleterious effects of alcohol abuse (as assessed by the investigator) or excessive alcohol consumption ( > 4 units/day for males, > 2 units/day for females)
• Known or suspected use of illicit drugs or drugs of abuse (allowed if medically prescribed or indicated) within 3 months of day 0
• If female: known pregnancy, or has a positive urine pregnancy test confirmed by a positive serum pregnancy test, or lactating
• Other concomitant disease, malignancy, or condition likely to significantly decrease life expectancy to less than the duration of the trial (e.g., moderate to severe congestive heart failure)
• Participation in another investigational drug, biologic, or medical device trial within 30 days prior to screening
• History of noncompliance with medical regimens, or subjects who are considered to be potentially unreliable
• Blood or plasma donation within 30 days prior to day 0
• Mental instability or incompetence such that the validity of informed consent or compliance with the trial is uncertain