Efficacy and Safety of Fenofibrate Combined With UDCA in PBC Patients With an Incomplete Biochemical Response to UDCA

Study Overview
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Brief Summary
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The purpose of this protocol is to conduct a trial in a selected population of patients with PBC based on an incomplete biochemical response after 12 months of UDCA therapy.

Detailed Description
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Primary biliary cholangitis is a chronic cholestatic liver disease, ursodeoxycholic acid (UDCA) is the only drug approved for the treatment of PBC. Although UDCA can improve the clinical outcomes in patients with PBC, about 40% of PBC patients show an incomplete biochemical response to this treatment, accordingly have a significantly increased risk of developing liver transplantation or death. Therefor there is a urgently needed for better therapies for these patients. The development of new treatments is therefore needed. The Fenofibrate is the candidate, there is now a substantial body of circumstantial evidence supporting that Fenofibrate is well tolerated and can improve biochemical response in PBC patients with incompleted response to UDCA. The purpose of this protocol is to conduct a trial in a selected population of patients with PBC based on an incomplete biochemical response after 12 months of UDCA therapy.

Official Title
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A Randomized Controlled Clinical Trial on the Efficacy and Safety of Fenofibrate Combined With Ursodeoxycholic Acid in PBC Patients With an Incomplete Biochemical Response to UDCA

Conditions
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Primary Biliary Cirrhosis

Intervention / Treatment
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* Drug: Fenofibrate
* Drug: UDCA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PBC Patient , previous treatment with UDCA 13-15 mg/kg/day for at least 1 year, showed incomplete biochemical response; Patients who showing an incomplete biochemical response to UDCA as defined by: ALP > 3ULN,AST> 2N ,total bilirubin >17 µmol/l after ≥ 12 months of UDCA at the dose of 13 - 15 mg/kg/day. 3,signed informed consent after careful review of information and study details. Exclusion Criteria: Hypersensitivity to fenofibrate Administration of the following drugs at any time during the 3 months prior to screening for the study: methotrexate, colchicines, azathioprine, systemic steroids. Decompensation PBC, such as recurrent variceal hemorrhage, uncontrolled encephalopathy or refractory ascites Anticipated need for liver transplantation within one year 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 Acute or chronic renal failure Known history of cholecystitis with intact gallbladder Pregnant or nursing women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: UDCA Standard treatment<br>All subjects will reiceive UDCA at a dose of 13-15mg/kg/d by oral for 12 months, and UDCA will be maintained after 12 months. | Drug: UDCA<br>* Ursodeoxycholic acid，the abbreviation UDCA, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria，it is the only FDA approved drug to treat PBC.<br>* Other names: Ursa，Urso, Urso Forte, Ursocol, Ursofalk,;|
| Experimental: Fenofibrate Combined with UDCA Treatment<br>All subjects will be treated with UDCA,13-15mg/kg/d, and Fenofibrate, 200mg/d by oral for 12 month, | Drug: Fenofibrate<br>* Fenofibrate is a drug of the fibrate class. it reduces both low-density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels, as well as increasing high-density lipoprotein (HDL) levels and reducing triglyceride levels.<br>* Other names: Antara, Fenoglide, Fibricor, Lipofen, Lofibra;Drug: UDCA<br>* Ursodeoxycholic acid，the abbreviation UDCA, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria，it is the only FDA approved drug to treat PBC.<br>* Other names: Ursa，Urso, Urso Forte, Ursocol, Ursofalk,;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Level of Alkaline Phosphatase(ALP) value | To analyze the clinical efficacy of UDCA combined with UDCA at 1 year compared to baseline values. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total bilirubin(TBIL) value | To analyze the clinical efficacy of UDCA combined with UDCA at 1 year compared to baseline values. | 12 months | 
| Aspartate aminotransferase(AST) value | To analyze the clinical efficacy of UDCA combined with UDCA at 1 year compared to baseline values. | 12 months | 
| Serum Level of Gamma-glutamyl transpeptidase (GGT) value | To analyze the clinical efficacy of UDCA combined with UDCA at 1 year compared to baseline values. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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UDCA, Fenofibrate