Obeticholic Acid (OCA) in Primary Sclerosing Cholangitis (PSC)

Inclusion Criteria:

• Must have had a diagnosis of PSC (based on cholangiography at any point in time).
• Alkaline phosphatase at Screening ≥2x ULN.
• Total bilirubin at Screening <2.5x ULN.
• For participants with concomitant inflammatory bowel disease (IBD):

1. Colonoscopy (if participant has a colon) or other appropriate endoscopicprocedure within 12 months of Day 0 confirming no dysplasia or colorectal cancer
2. Participants with Crohn's Disease (CD) must have been in remission as defined bya Crohn's Disease Activity Index (CDAI) <150
3. Participants with ulcerative colitis (UC) must either have been in remission orhave had mild disease. Remission was defined as a partial Mayo score of ≤2 withno individual sub-score exceeding 1. Mild disease was defined as a partial Mayoscore ≤3 with no individual sub-score exceeding 1 point.

• For participants being administered UDCA as part of their standard of care, the dosemust have been stable for ≥3 months prior to, and including, Day 0 and must not haveexceeded 20 mg/kilograms/day during this time.
• Participants being administered biologic treatments (for example, anti-tumor necrosisfactor or anti-integrin monoclonal antibodies), immunosuppressants, systemiccorticosteroids, 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.
• Contraception: female participants of childbearing potential must have used ≥1effective method (≤1% failure rate) of contraception during the trial and until 4weeks following the last dose of IP (including LTSE doses).

Exclusion Criteria:

• Evidence of a secondary cause of sclerosing cholangitis at Screening.
• Immunoglobulin G4 (IgG4) >4x ULN at Screening or evidence of IgG4 sclerosingcholangitis.
• Small duct cholangitis in the absence of large duct disease.
• Presence of clinical complications of chronic liver disease or clinically significanthepatic decompensation, including:
• Current Child Pugh classification B or C
• History of, or current diagnosis or suspicion of, cholangiocarcinoma or otherhepatobiliary malignancy, or biliary tract dysplasia.
• History of liver transplantation, or current model of end stage liver diseasescore ≥12
• History of, or current, cirrhosis with complications, including history orpresence of spontaneous bacterial peritonitis hepatocellular carcinoma or hepaticencephalopathy (as assessed by the Investigator)
• Current known portal hypertension with complications, including known gastric orlarge esophageal varices, poorly controlled or diuretic resistant ascites,history of variceal bleeds, or related therapeutic or prophylactic interventions (for example, beta blockers, insertion of variceal bands or transjugularintrahepatic portosystemic shunt).
• History of, or current, hepatorenal syndrome (type I or II) or Screening serumcreatinine >2 mg/deciliter (178 micromoles/liter [L]).
• Platelet count <50 x 10^9/L.
• Current clinical evidence of dominant strictures that were considered clinicallyrelevant in the opinion of the Investigator or current biliary stent at Screening.
• Current cholecystitis or evidence of current biliary obstruction due to gallstones.Asymptomatic gallstones that were not considered a safety risk in the opinion of theInvestigator might have been acceptable, subject to discussion and agreement with theMedical Monitor.
• 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, primarybiliary cholangitis (PBC), alcoholic liver disease, non-alcoholic fatty liver disease,autoimmune hepatitis, hepatitis B virus (unless seroconverted and no positiveHepatitis B Virus deoxyribonucleic acid), hepatitis C virus and overlap syndrome.
• Known Gilbert's syndrome or history of elevations in unconjugated (indirect) bilirubin >ULN or unconjugated (indirect) bilirubin >ULN at Screening.
• Known history of human immunodeficiency virus infection.
• Currently experiencing, or experienced within ≤3 months of Screening, pruritusrequiring systemic or enteral treatment.
• Known or suspected acute cholangitis in the 3 months prior to, and including, Day 0including cholangitis treated with antibiotics.
• Administration of antibiotics is prohibited ≤1 month of Day 0 (unless participant wason a stable prophylaxis dose for at least 3 months prior to Day 0).
• Administration of the following medications was prohibited ≤6 months of Day 0 andthroughout the trial: fenofibrate or other fibrates and potentially hepatotoxicmedications (including alpha-methyl-dopa, sodium valproic acid, isoniazide, ornitrofurantoin).
• IBD flare during Screening (up to and including Day 0), where "flare" was defined asfollows:
• UC flare: partial Mayo Score ≥5, and
• CD flare: CDAI ≥250
• Evidence of deleterious effects of alcohol abuse (as assessed by the Investigator) orexcessive 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 medicallyprescribed or indicated) within 3 months of Day 0.
• If female: known pregnancy, or had a positive urine pregnancy test (confirmed by apositive serum pregnancy test), or lactating.
• Other concomitant disease, malignancy, or condition likely to significantly decreaselife expectancy to less than the duration of the trial (for example, moderate tosevere congestive heart failure).
• Participation in another investigational drug, biologic, or medical device trialwithin 30 days prior to Screening.
• History of noncompliance with medical regimens, or participants who were considered tobe potentially unreliable.
• Blood or plasma donation within 30 days prior to Day 0.
• Mental instability or incompetence such that the validity of informed consent orcompliance with the trial was uncertain.