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

NCT04309773 | Unknown Phase 3

• 1 other identifier: APHP180668
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Primary Sclerosing Cholangitis; Cholestasis

Keywords

Primary sclerosing cholangitis; Persistent cholestasis; Bezafibrates; Fibrates; UDCA

Outcome Measures

Primary Outcomes (1)

• To assess the efficacy of 24-month treatment with bezafibrate (400 mg/day) versus placebo in addition to standard UDCA therapy in Primary Sclerosing Cholangitis (PSC).

  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:

  At 24 months

Secondary Outcomes (6)

• Percentage of patients with clinical or biological adverse events

  At 24 months

• Quality of life of PSC patients

  At 12 months and 24 months

• Score for pruritus

  At 12 months and 24 months

• Fatigue score

  At 12 months and 24 months

• Level of liver biochemical parameters between the two groups of patient

  between month 0 and month 24

Study Arms (2)

Bezafibrate in addition to standard UDCA therapy

EXPERIMENTAL

Bezafibrate (400mg) in addition to standard 15-20 mg/kg/day UDCA therapy ("experimental" arm)

Drug: Bezafibrate (400mg) in addition to standard 15-20 mg/kg/jour UDCA therapy

Placebo of Bezafibrate in addition to standard UDCA therapy

PLACEBO COMPARATOR

Placebo of Bezafibrate in addition to standard 15-20 mg/kg/day UDCA therapy

Drug: Placebo of Bezafibrate in addition to standard UDCA therapy

Interventions

Bezafibrate (400mg) in addition to standard 15-20 mg/kg/jour UDCA therapy DRUG

Bezafibrate (400mg) in addition to standard 15-20 mg/kg/jour UDCA therapy Treatment duration : 24 months Bezafibrate/AUDC : daily oral dose

Bezafibrate in addition to standard UDCA therapy

Placebo of Bezafibrate in addition to standard UDCA therapy DRUG

Placebo of Bezafibrate (400mg) in addition to standard 15-20 mg/kg/Day UDCA therapy Treatment duration : 24 months Placebo/AUDC : daily oral dose

Placebo of Bezafibrate in addition to standard UDCA therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Using contraceptive in childbearing women
• Affiliation to a social security system (AME excepted)
• Signed informed consent

You may not qualify if:

• 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
• 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)
• 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 or established or suspected hepatobiliary carcinoma.
• Any severe comorbidity that may reduce life expectancy

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hepatology department - Hopital Saint Antoine

Paris, 75012, France

RECRUITING

MeSH Terms

Conditions

Cholangitis, Sclerosing; Cholestasis

Interventions

Bezafibrate

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Benzoates; Acids, Carbocyclic; Chlorobenzoates; Phenyl Ethers; Ethers; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Study Officials

• Olivier CHAZOUILLERES, professor

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Olivier CHAZOUILLERES, professor

CONTACT

+ 33149282380; olivier.chazouilleres@aphp.fr

Christophe CORPECHOT, docteur

CONTACT

00 33 1 49 28 28 36; christophe.corpechot@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2019
• First Posted: March 16, 2020
• Study Start: April 6, 2021
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2025
• Last Updated: May 10, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)