Fenofibrate for Compensated Cirrhosis Patients With Primary Biliary Cholangitis

Study Overview
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Brief Summary
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The main objectives of the study were to assess the effects of fenofibrate on serum alkaline phosphatase, as a composite endpoint and on safety in participants with primary biliary cholangitis (PBC).

Detailed Description
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This is a multi-center, randomized, placebo-controlled, parallel-group study that aims to assess the efficacy and safety of fenofibrate in patients with compensated cirrhosis PBC who had an inadequate biochemical response to UDCA. Fenofibrate or placebo 200 mg will be daily administered in combination with UDCA 13-15 mg/kg/d for 12 months.

Official Title
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Fenofibrate Combined With Ursodeoxycholic Acid in Compensated Cirrhosis Patients With Primary Biliary Cholangitis Who Had an Inadequate Response to Ursodeoxycholic Acid

Conditions
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Primary Biliary Cholangitis

Intervention / Treatment
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* Drug: Fenofibrate 200mg
* Drug: Placebo
* Drug: UDCA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have provided written informed consent Age 18-75 years; BMI 17-28 kg/m2 Male or female with a diagnosis of PBC, by at least two of the following criteria: History of AP above ULN for at least six months; Positive AMA titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies; Documented liver biopsy result consistent with PBC. Diagnosis of compensated cirrhosis, as demonstrated by the presence of ≥ 1 of the following 4 diagnostic factor The histology was consistent with the diagnosis of liver cirrhosi; Endoscopy shows esophageal and gastric varices or ectopic varices of digestive tract, excluding non cirrhotic portal hypertension; Ultrasound or CT and other imaging examinations indicate the characteristics of liver cirrhosis or portal hypertension, such as splenomegaly, portal vein ≥ 1.3 cm, or liver stiffness measured by transient elastography>16.9 kPa; Abnormal laboratory inspection indicators (2 out of 4): 1) PLT < 100 × 109/L, and no other reason can be explained; 2) Serum albumin<35 g/L, excluding malnutrition or kidney disease and other causes; 3) INR > 1.3 or PT prolongation (stop thrombolytic or anticoagulant drugs for more than 7 days); 4) AST/PLT (APRI)>2） Incomplete response to UDCA defined by ALP > 1.67 x ULN Taking UDCA for at least 6 months (stable dose for ≥ 3 months) prior to Day 0 Exclusion Criteria: History or presence of other concomitant liver diseases. ALT or AST > 5×ULN, TBIL > 3×ULN. If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating. Allergic to fenofibrate or ursodeoxycholic acid. Taking hepatotoxic drugs (e.g., dapsone, erythromycin, fluconazole, ketoconazole, rifampicin) for more than 2 weeks within 6 months, and long-term hormonal users. Recurrent variceal bleeding, poorly controlled hepatic encephalopathy or refractory ascites. Patients with a history of severe cardiac, cerebrovascular, renal, respiratory disease or functional failure, and psychiatric disorders (including those due to alcohol and drug abuse). Creatinine >1.5×ULN and creatinine clearance <60 ml/min. Currently using statins (such as pravastatin, fluvastatin, and simvastatin), other fibrates (such as gemfibrozil and bezafibrate), and drugs structurally similar to fenofibrate (like ketoprofen). Planned to receive an organ transplant or an organ transplant recipient. Needing Liver transplantation within 1 year according to the Mayo Rick score. Any other condition(s) that would compromise the safety of the subject or compromise

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo-UDCA<br>1 tablet/ day and UDCA 13-15mg/kg/day for 12 months | Drug: Placebo<br>* 1 tablet/ day<br>Drug: UDCA<br>* UDCA 13-15mg/kg/day<br>|
| Experimental: Fenofibrate-UDCA<br>Fenofibrate 200 mg/day and UDCA 13-15mg/kg/day for 12 months | Drug: Fenofibrate 200mg<br>* Fenofibrate 200mg/day<br>Drug: UDCA<br>* UDCA 13-15mg/kg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with biochemical response | The normalisation of Alkaline Phosphatase | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients having biochemical response | The normalisation of Alkaline Phosphatase at 4, 12, 24, and 36 weeks. | 4, 12, 24 and 36weeks | 
| Assessment of the pruritus and fatigue | Change From Baseline in Fatigue and Pruritus as Assessed by Visual Analogue Scale (VAS) Total Score for Fatigue and Pruritus. (0-10, higher scires mean a worse outcome) | 4, 12, 24, 36, and 48 weeks | 
| Percentage of patients having biological or clinical adverse events | Increase of creatinine | 4, 12, 24, 36, and 48 weeks | 
| Percentage of patients having biological or clinical adverse events | Increase Blood urea nitrogen | 4, 12, 24, 36, and 48 weeks | 
| Percentage of patients having biological or clinical adverse events | Increase of creatine kinase | 4, 12, 24, 36, and 48 weeks | 
| Percentage of patients having biological or clinical adverse events | Increase ALT and AST. | 4, 12, 24, 36, and 48 weeks | 
| Survival without transplantation and hepatic impairment | Occurrence of ascites, variceal bleeding, hepatic encephalopathy, liver-transplantation, or death. | 48 weeks |