Patient description: The patient is a 53-year-old man complaining of frequent headaches, generalized bone pain and difficulty chewing that started 6 years ago and is getting worse. Examination shows bilateral swellings around the molars. The swellings have increased since his last examination. Several extraoral lesions of the head and face are detected. The swellings are non-tender and attached to the underlying bone. Further evaluation shows increased uptake of radioactive substance as well as an increase in urinary pyridinoline. The serum alkaline phosphatase is 300 IU/L (the normal range is 44- 147 IU/L). The patient's sister had the same problems. She was diagnosed with Paget's disease of bone when she was 52 years old. The diagnosis of Paget's Disease of Bone is confirmed and Bisphosphonate will be started as first-line therapy.

Clinical trial eligibility criteria: eligible ages (years): 18.0-75.0,  Primary Sclerosing Cholangitis (PSC) 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 PSC (based on cholangiography at any point in time) Alkaline phosphatase (ALP) at Screening ≥ 2x ULN Total bilirubin at Screening < 2.5x ULN For subjects with concomitant inflammatory bowel disease (IBD): 1. Colonoscopy (if subject has a colon) or other appropriate endoscopic procedure within 12 months of Day 0 confirming no dysplasia or colorectal cancer 2. Subjects with Crohn's Disease (CD) must be in remission as defined by a Crohn's Disease Activity Index (CDAI) <150. 3. 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 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 Contraception: female subjects of childbearing potential must use ≥ 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)  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, or current model of end stage liver disease 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 (e.g., beta blockers, insertion of variceal bands or transjugular intrahepatic portosystemic shunt [TIPS]) History of, or current, hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/dL (178 μmol/L)