Efficacy of 24 Month of Bezafibrate in Primary Sclerosing Cholangitis With Persistent Cholestasis Despite Ursodeoxycholic Acid Therapy

Inclusion Criteria: * Males or females ≥ 18 and ≤ 75 years * Large duct PSC verified by retrograde, operative, percutaneous or magnetic resonance cholangiography (MRC) demonstrating intrahepatic and /or extrahepatic biliary duct changes consistent with PSC * Colonoscopy (already done or scheduled before randomization) within the last 5 years (or within 6 months if IBD is associated to PSC) with neither cancer nor allgrade dysplasia or endoscopy of the ileal reservoir (already done or scheduled before randomization) within the last 2 years in patients with ileo-anal anastomosis * ALP ≥ 1.5 ULN at baseline * Treatment with stable dose of UDCA (15-20 mg/kg/d) for ≥ 6 months before inclusion (rounded to the nearest unit, e.g 14.5 mg/kg/d would be 15mg/kg/d). * Using contraceptive in childbearing women * Affiliation to a social security system (AME excepted) * Signed informed consent Exclusion Criteria: * Child-Pugh score B or C * Ascites or digestive hemorrhage (or history of) * Total bilirubin in the last 3 months \> 50 μmole/L (3 mg/dl) * Gilbert syndrome defined as unconjugated bilirubinemia \> 12 μmol/L * Albumin in the last 3 months \< ULN (according to the laboratory reference value) * Prothrombin index in the last 3 months \< 70% * Platelets count in the last 3 months \< 100000/mm3 * ALT or AST \> 5 ULN in the last 3 months * Prior liver transplantation * Treatment with a fibrate within the last 3 months inclusion or with a statin at inclusion * Current active IBD defined as either current use of systemic corticosteroid therapy \> 10 mg/day or budesonide \> 3 mg /day or immunosuppressive drugs (cyclosporine, tacrolimus, mycophenolate mofetil, mTor inhibitors, JAK inhibitors) or a partial Mayo score \> 2 in patients with ulcerative colitis (UC) or a Crohn's Disease Activity Index (CDAI) \> 150 in patients with Crohn's disease (CD) * Dose change of treatment for associated IBD ≤3 months prior to inclusion * Current or history of colonic cancer or all-grade dysplasia described at the last colonoscopy (Patients with a history of colon cancer and treated by total colectomy without recurrence for at least 5 years are eligible) * Any other cause of liver damage ((positive test for HBV, HCV, or HIV, excessive alcohol consumption, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, celiac disease, autoimmune hepatitis defined by the presence of at least 2 of the 3 following criteria; 1) AST or ALT \> 5 ULN, 2) Positive anti smooth muscle auto antibodies or serum IgG \> 1.5 ULN, 3) interface hepatitis on liver biopsy) * Secondary causes of sclerosing cholangitis including IgG4-associated cholangitis (elevated serum IgG4 \> 4 ULN) * History of acute cholangitis in the last 3 months prior to inclusion or current acute cholangitis * Endoscopic treatment for bile duct stenosis ≤ 3 months prior to inclusion or planned within 3 months post randomization date * History of or established or suspected hepatobiliary carcinoma. * Any severe comorbidity that may reduce life expectancy * History of malignancy diagnosed or treated within 2 years (recent localized treatment of squamous or non-invasive basal skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to Screening) * Known hypersensitivity to bezafibrate, any of the components of Befizal© or other fibrates * Known photosensitivity or photoallergy reactions to fibrate * Patient with congenital galactosemia, glucose malabsorption, or lactase deficiency because of presence of lactose in 400 mg SR tablets of bezafibrate and in placebo tablets * Pregnancy (or desire for) * Renal insufficiency (clearance \< 60 ml/min or serum creatinine level \> 130 μmole/L) * Breastfeeding * Participation in any other interventional study or in the exclusion period any other interventional study * Autoimmune hepatitis defined by the presence of interface hepatitis documented on liver biopsy and at least 1 of the 2 following criteria: 1) AST or ALT \> 5 ULN, 2) Positive anti smooth muscle auto antibodies or serum IgG \> 1.5 ULN * Results of colonoscopy not available or \> 5 years (or \> 6 months if IBD is associated to PSC) or with cancer or all-grade dysplasia or results of endoscopy of the ileal reservoir not available or \> 2 years in patients with ileo-anal anastomosis Randomization exclusion criteria: * Positive test for HBV (positive HBs Ag), HCV (positive HCV RNA), or HIV (positive serology) * Pregnancy (or desire for in the 2 next years) * Secondary causes of sclerosing cholangitis including IgG4-associated cholangitis (elevated serum IgG4 \> 4 ULN) * Autoimmune hepatitis defined by the presence of interface hepatitis documented on liver biopsy and at least 1 of the 2 following criteria: 1) AST or ALT \> 5 ULN, 2) Positive anti smooth muscle auto antibodies or serum IgG \> 1.5 ULN * Current acute cholangitis