Bezafibrate for Primary biliary cholangitis

Inclusion criteria

• {"criterion_text":"- 1. Age ≥ 18 and < 80 years\n- 7. Signed informed consent\n- 2. Diagnosis of PBC based on at least 2 of the following criteria (EASL clinical practice guidelines 2017:\n- a. Elevated ALP level\n- b. Presence of antimitochondrial antibody (immunofluorescence titer ≥ 1:40 or positive antigen-specific test), specific antinuclear immunofluorescence (nuclear dots or perinuclear rims) or positive antigen-specific test for anti-gp210 or anti-Sp100 antibodies\n- c. Records of histologic features suggestive of, or compatible with PBC\n- 3. UDCA therapy for the past 12 months (stable dose ≥ 12 mg/kg/d for ≥ 3 months prior to inclusion)\n- 4. Biochemical evidence of non-optimal response to UCDA (i.e. ALP > 1.0 xULN, or GGT > 3.0 xULN, or ALT or AST > 1.0 xULN, or total and conjugated bilirubin > 1.0 xULN) between 6 months and 2 weeks before inclusion visit. If total bilirubin is within the normal range, measurement of conjugated bilirubin is not mandatory.\n- 5. Women of child-bearing potential (WOCBP), i.e., fertile, following menarche and until becoming post-menopaused unless permanently sterile, who are sexually active have to apply an effective method of birth control*, throughout the study period and for 90 days following the last dose of study treatment. *the list of acceptable method of contraception is in addenda 18.1\n- 6. Affiliation to a social security system (AME excepted)"}

Exclusion criteria

• {"criterion_text":"- 1.\tAny of the following signs of advanced chronic liver disease: Total bilirubin > 2.0 xULN; Serum albumin < 32 g/l; Platelet count < 100,000/mm3; INR > 1.3 or prothrombin index < 60%; in the last 6 months; Child-Pugh score B or C; MELD score ≥ 14; History ≤ 24 months or presence of cirrhotic decompensation; Patients on the waiting list for LT\n- 10. Gilbert’s syndrome or chronic hemolysis (hyperbilirubinemia with an unconjugated to total bilirubin ratio ≥ 75%)\n- 11. History of or established or suspected hepatocellular carcinoma\n- 12. History of malignancy diagnosed or treated within 2\n- 13. Any severe comorbidity that may reduce life expectancy ≤ 2 years\n- 14. Pregnancy or lactating\n- 15. Known intolerance to bezafibrate\n- 16. Known hypersensitivity to bezafibrate, any of the components of Befizal© or other fibrates\n- 17. Known photosensitivity reactions or photoallergic reactions to fibrates\n- 18. Patient with congenital galactosemia, glucose malabsorption, or lactase deficiency because of presence of lactose in LP tablets of bezafibrate\n- 19. Participation in any other interventional study in the past 6 months (RIPH1, clinical investigation or clinical trial)\n- 2. GFR estimated by CKI-EPI equation < 60 mL/min in the last 6 months\n- 20. Any of the following medications used in the past 3 months before inclusion: bezafibrate, fenofibrate, ciprofibrate, gemfibrozil, obeticholic acid, budesonide, any other systemic corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, sirolimus, everolimus, methotrexate.\n- 21. Use of statins in the month before inclusion\n- 3. CPK > 5.0 xULN in the last 6 months\n- 4. AST or ALT > 3.0 xULN in the last 6 months\n- 5. History of LT\n- 6. Features of autoimmune hepatitis (AIH) overlap syndrome (either past or newly diagnosed during follow up)\n- 7. Any other chronic hepatic comorbidities (HIV, HCV, HBV, NASH, alcoholic liver disease, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, celiac disease)\n- 8. Untreated hypo or hyperthyroidism (Hashimoto or Graves autoimmune thyroiditis)\n- 9. Conditions that may cause non-hepatic increases in ALP (Paget’s disease, osteodystrophy, hyperparathyroidism, dysglobulinemia)"}

Primary endpoints

• {"endpoint_text":"- • Proportion of patients with a complete biochemical response defined by normal serum levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), aminotransferases (AST, ALT), and total bilirubin at 48 weeks of treatment.","definition_or_measurement_approach":"Complete biochemical response defined by normal serum levels of ALP, GGT, AST, ALT and total bilirubin measured at Week 48 (serum laboratory tests at 48 weeks)."}

Secondary endpoints

• {"endpoint_text":"- 1. Changes from baseline to W48 in itch intensity mean of the last 24h assessed by NRS as recommended by IFSI SIG / EADV Task Force Pruritus.","definition_or_measurement_approach":"Itch intensity: mean of the last 24 hours assessed by Numeric Rating Scale (NRS) at baseline and Week 48, following IFSI SIG / EADV Task Force Pruritus recommendations."}
• {"endpoint_text":"- 2. Proportion of patients with normal levels of ALP at W48.","definition_or_measurement_approach":"Proportion of patients whose alkaline phosphatase (ALP) is within normal range at Week 48 (laboratory measurement at Week 48)."}
• {"endpoint_text":"- 3. Changes from baseline to W48 in LSM assessed by Fibroscan.","definition_or_measurement_approach":"Liver stiffness measurement (LSM) assessed by Fibroscan at baseline and Week 48; analysis of change from baseline to Week 48."}

France

Earliest CTIS Part Ii Submission Date

24-06-2024

Latest Decision Or Authorization Date

11-03-2026

Processing Time Days

625

Number Of Sites

30

Number Of Participants

130

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France