Fenofibrate for Compensated Cirrhosis Patients with Primary Biliary Cholangitis

Phase 2

Recruiting

• Conditions: Primary Biliary Cholangitis
• Interventions: Drug: Placebo; Drug: Fenofibrate 200mg; Drug: UDCA

• Registration Number: NCT05749822
• Lead Sponsor: Xijing Hospital of Digestive Diseases

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-12-29
• Study Start: 2023-02-17
• Study First Submitted QC: 2023-02-28
• Study First Posted: 2023-03-01
• Status Verified: 2024-04
• Last Update Submitted: 2024-12-23
• Last Update Posted: 2024-12-27
• Primary Completion: 2025-12-01
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 104

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:

  1. History of AP above ULN for at least six months;
  2. Positive AMA titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies;
  3. Documented liver biopsy result consistent with PBC.

• Diagnosis of compensated cirrhosis, as demonstrated by the presence of ≥ 1 of the following 4 diagnostic factor

  1. The histology was consistent with the diagnosis of liver cirrhosi;
  2. Endoscopy shows esophageal and gastric varices or ectopic varices of digestive tract, excluding non cirrhotic portal hypertension;
  3. 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;
  4. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo-UDCA	Placebo	1 tablet/ day and UDCA 13-15mg/kg/day for 12 months
Placebo-UDCA	UDCA	1 tablet/ day and UDCA 13-15mg/kg/day for 12 months
Fenofibrate-UDCA	Fenofibrate 200mg	Fenofibrate 200 mg/day and UDCA 13-15mg/kg/day for 12 months
Fenofibrate-UDCA	UDCA	Fenofibrate 200 mg/day and UDCA 13-15mg/kg/day for 12 months

Primary Outcome Measures

Name	Time	Method
Percentage of patients with biochemical response	48 weeks	The normalisation of Alkaline Phosphatase

Secondary Outcome Measures

Name	Time	Method
Percentage of patients having biological or clinical adverse events	4, 12, 24, 36, and 48 weeks	Increase ALT and AST.
Survival without transplantation and hepatic impairment	48 weeks	Occurrence of ascites, variceal bleeding, hepatic encephalopathy, liver-transplantation, or death.
Percentage of patients having biochemical response	4, 12, 24 and 36weeks	The normalisation of Alkaline Phosphatase at 4, 12, 24, and 36 weeks.
Assessment of the pruritus and fatigue	4, 12, 24, 36, and 48 weeks	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)

Trial Locations

Locations (5)

Xiangya Hospital Central South University; 🇨🇳 Changsha, Hunan, China

Yan'an University Affiliated Hospital; 🇨🇳 Yanan, Shaanxi, China

Sichuan Provincial People's Hospital; 🇨🇳 Chengdu, Sichuan, China

Tianjin Medical University General Hospital; 🇨🇳 Tianjin, China

Xijing Hospital; 🇨🇳 Xi'an, Shaanxi, China