Clinical Trials

Inclusion Criteria 

• Subjects must meet all of the following to be eligible to participate:
  • 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, and must have had a cholangiography within the past 12 months
  • ALP at screening ≥ 2x ULN
  • Total bilirubin at screening < 2.5x ULN
    • Subjects will be stratified according to total bilirubin level and no more than 25% of subjects recruited will have a total bilirubin >1.5x ULN and <2.5x ULN at screening
  • For subjects with concomitant IBD
    • Colonoscopy 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
      • Mild disease is defined as a partial Mayo score ≤3 with no individual sub-score exceeding 1 point
  • For subjects being administered UDCA 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 will be stratified according to UDCA use and no more than 50% of subjects administering UDCA at day 0 will be recruited
  • For subjects being administered biologic treatments (eg, Anti-TNF or anti-integrin monoclonal antibodies), immunosuppressants or systemic corticosteroids they 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 ≥1 effective method of contraception during the trial and until 4 weeks following the last dose of IP (including LTSE doses)

Exclusion Criteria

• Subjects will be excluded from trial participation if they meet any of the following:
  • 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, or current diagnosis or suspicion of, cholangiocarcinoma or other hepatobiliary malignancy, or biliary tract dysplasia
    • History of liver transplantation, current placement on a liver transplant list, or current model of end stage liver disease (MELD) score ≥ 12
    • History of, or current cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis, hepatocellular carcinoma or hepatic encephalopathy (as assessed by the investigator)
    • Current known portal hypertension with complications, including
      • Known gastric or large esophageal varices
      • Poorly controlled or diuretic resistant ascites
      • History of variceal bleeds
      • Or related therapeutic or prophylactic interventions (eg, beta blockers, insertion of variceal bands, or transjugular intrahepatic portosystemic shunt)
    • History of, or current hepatorenal syndrome (type I or II) or screening serum creatinine > 2 mg/dL (178 μmol/L)
    • Platelet count <50 x109/L
  • Clinical evidence of dominant stricture as evidenced by cholangiography or other appropriate imaging modality within the 12 months prior to day 0
  • 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
  • Known Gilbert’s syndrome or elevations in unconjugated (indirect) bilirubin >ULN
  • Known history of human immunodeficiency virus (HIV) infection
  • Currently experiencing, or experienced within ≤1 month of screening, moderate to severe pruritus requiring systemic or enteral treatment, or any history of severe pruritus
  • 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
  • Administration of the following medications is prohibited ≤ 6 months of day 0 and throughout the trial
    • Fenofibrate or other fibrates 
    • Potentially hepatotoxic medications including
      • α-methyl-dopa
      • Sodium valproic acid
      • Isoniazide
      • Nitrofurantoin
  • IBD flare during screening (up to and including day 0), where "flare" is defined as follows
    • UC flare: partial Mayo Score ≥ 5; and
    • 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, a 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 (eg, 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