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

• Status: Recruiting
• Trial end date: 2024-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The objectives of this study are to evaluate the effect of bezafibrate treatment compared to placebo on efficacy and safety in patients with primary sclerosing cholangitis (PSC) and persistent cholestasis despite ursodeoxycholic acid therapy

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Bezafibrate; Ursodeoxycholic Acid

Criteria

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 within the last 5 years (or within 3 months if IBD is associated to PSC) with no cancer nor all-grade dysplasia

• ALP ≥ 1.5 ULN at baseline

• Treatment with UDCA (15-20 mg/kg/d) for ≥ 6 months before inclusion.

• 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 < 35 g/L

• 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) or biologics (vedolizumab, ustekinumab) 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

• 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

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 at least 2 of the 3 following criteria; AST or ALT > 5 ULN, Positive anti smooth muscle auto antibodies or serum IgG > 1.5 ULN, interface hepatitis on liver biopsy

• Current acute cholangitis