Fenofibrate for Patients With Primary Biliary Cirrhosis Who Had An Inadequate Response to Ursodeoxycholic Acid

Ursodeoxycholic acid (UDCA) has been the only treatment for PBC approved by US and European drug administrations. Long-term use of UDCA(13-15 mg/kg/day) in patients with PBC improves serum liver biochemistries and survival free of liver transplantation However, about 40% of patients do not respond to UDCA optimally as assessed by known criteria for biochemical response. Those patients represent the group in need for additional therapies, having increased risk of disease progression and decreased survival free of liver transplantation. Both lab research and some clinical studies suggest that fenofibrate could improve cholestasis in multiple ways including reduce of bile acid synthesis, increase of biliary secretion and anti-inflammation effect. Here we start a random, open and parallel clinical research to explore the effect of fenofibrate in the PBC treatment.

Study Overview

• Status: Recruiting
• Conditions: Primary Biliary Cirrhosis
• Intervention / Treatment: Drug: UDCA; Drug: Fenofibrate

• Study Type: Interventional
• Enrollment (Anticipated): 104
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ying Han, Ph.D; Phone Number: 86-29-84771539; Email: hanying@fmmu.edu.cn
• Study Contact Backup: Name: Yongquan Shi, Ph.D; Phone Number: 86-29-84771515; Email: shiyquan@fmmu.edu.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Xijing Hosipital
      • Contact: Ying Han, Ph.D; Phone Number: 86-29-84771539; Email: hanying@fmmu.edu.cn
      • Contact: Yongquan Shi, Ph.D; Phone Number: 86-29-84771515; Email: shiyquan@fmmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent
2. Patient with PBC defined by 2 in 3 of the following criteria: a.Positive antimitochondrial antibody type M2; b.Abnormal serum alkaline phosphatases (ALP > 1,5N) and aminotransferase (AST or ALT > 1N) activities; c.Histological hepatic injuries consistent with PBC.
3. Had been treated with UDCA more than 6 months, and failed to achieve a complete biochemical response.

Exclusion Criteria:

1. Pregnancy or desire of pregnancy.
2. Breast-feeding.
3. Co-existing liver diseases such as acute or chronic viral hepatitis, alcoholic liver disease, choledocholithiasis, autoimmune hepatitis, biopsy-proven non-alcoholic fatty liver disease, Wilson's disease and hemochromatosis.
4. History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy, or poorly controlled ascites).
5. History of urolithiasis, nephritis or renal failure (clearance of creatinine < 60 ml/mn).
6. Hepatotoxic drugs use before recruiting.
7. Fenofibrate anaphylaxis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fenofibrate + UDCA; Fenofibrate in combination with ursodeoxycholic acid	Drug: UDCA; Drug: Fenofibrate
Active Comparator: Monotherapy; UDCA alone	Drug: UDCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of patients with complete biochemical response	Normalization of alkaline phosphatase (ALP) or decrease of ALP by more than 40% compared to the baseline.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in liver stiffness status measured by magnetic resonance elastography.	The change of liver stiffness status at the end of the study compared to baseline checked by magnetic resonance elastography.	Week 48
Change in liver biopsy examinations according to conventional Ludwig system.	Histological evolution will be checked by liver biopsy at the end of the study to compare with baseline histological status. The Ludwig histological classification schemes will be used, which categorised the disease into four stages.	Week 48
Change in serum levels of ALP compared to the baseline.	Absolute change in serum levels of ALP compared to the baseline.	Weeks 0, 4, 8, 12, 24, and 48
Change in serum levels of bilirubin compared to the baseline.	Absolute change in serum levels of bilirubin compared to the baseline.	Weeks 0, 4, 8, 12, 24, and 48
Change in serum levels of transaminase compared to the baseline.	Absolute change in serum levels of transaminase compared to the baseline.	Weeks 0, 4, 8, 12, 24, and 48
Change in GLOBE risk scores after treatment.	The prognostic scores will be calculated at entry and end of study by GLOBE scoring system, which calculated based on serum values of bilirubin, ALP, albumin and platelet count after 1 year of treatment and age at baseline.	Week 48

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in symptom-pruritus.	The symptom of pruritus will be evaluated by questionnaire before enrolment and at the end of the study.	Week 24
Change in symptom-fatigue.	The symptom of fatigue will be evaluated by Fatigue Impact Scale before enrolment and at the end of the study.	Week 24
Change in serum Immunoglobulin M Levels.	Absolute change in serum levels of Immunoglobulin M compared to the baseline.	Week 24

Collaborators and Investigators

• Sponsor: Xijing Hospital of Digestive Diseases

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: January 28, 2016
• First Submitted That Met QC Criteria: June 30, 2016
• First Posted (Estimate): July 6, 2016

Study Record Updates

• Last Update Posted (Actual): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 27, 2022
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Fenofibrate; PBC; UDCA
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Fibrosis; Liver Cirrhosis; Liver Cirrhosis, Biliary; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Fenofibrate
• Other Study ID Numbers: KY20151230-5