Adult patients with primary sclerosing cholangitis
Conditions
Interventions
Trade Name: BEFIZAL L.P. 400 mg, comprimé enrobé à libération prolongée
Product Name: bezafibrate
Product Code: C10AB02
Pharmaceutical Form: Tablet
INN or Proposed INN: BEZAFIBRATE
CAS Number: 41859-6
Sponsors
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion 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 women of childbearing potential. Women of childbearing potential, i.e. fertile, following menarche and until becoming post-menopaused unless permanently sterile, who are sexually active have to apply a highly effective method of birth control with a low failure rate (i.e., less than 1% per year) when used constantly and correctly. • Affiliation to a social security system (AME excepted) • Signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 52 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 52
Exclusion criteria
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of 24-month treatment with bezafibrate (400 mg SR/d) versus placebo in addition to standard UDCA therapy in primary sclerosing cholangitis;Secondary Objective: 1. To compare between groups: a) Components of the primary composite outcome at M24 b) Adverse effects including IBD activity hepatic, muscular, and kidney function. c) Quality of life and scores for pruritus and fatigue at M12 and M24 d) Changes in liver tests between M0 and M24 e) Occurrence of clinical events and transplant-free survival 2. Exploratory objectives: - Changes in serum markers of fibrosis (ELF score and Pro-C3) and cholangiographic abnormalities between M0 and M24 - Course of biomarkers (including microbiota) and correlation with observed effects between M0 and M24 - Need for endoscopic procedures between M0 and M24;Primary end point(s): Proportion of patients with serum Alkaline Phosphatase < 1.5 ULN and a reduction of at least 15% from baseline at M24 and normal serum bilirubin and no increase of liver stiffness at M24 compared to Baseline (delta M24–M0 = 0).;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To compare between groups a) Components of the primary composite outcome analyzed separately: Proportion of patients with: • serum Alkaline Phosphatase 100 µmol/L for at least 3 months). PSC Prognostic scores including the MELD score, the Revised PSC Mayo Risk Score, the Hannover Score and the Amsterdam-Oxford prognostic model (M0, M12, M24) 2. Exploratory endpoints (M0, M12, M24) • Course of: - serum markers of liver fibrosis (ELF score and Pro-C3) - cholangiographic abnormalities - biological markers of liver function - bile acids and cytokines - microbiota (M0-M12-M24) (dietetary questionnaire and questionnaire accompanying the stool sample) • Need for endoscopic treatment of biliary strictures;Timepoint(s) of evaluation of this end point: 24 months | — |
Countries
France
Contacts
Public ContactSophie COURTIAL-DESTEMBERT
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Outcome results
None listed