Fenofibrate for Compensated Cirrhosis Patients With Primary Biliary Cholangitis

Primary Biliary Cholangitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05749822
• Other study ID #: KY20222293-C-1
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: February 17, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2024
• Source: Xijing Hospital of Digestive Diseases
• Contact: Yulong Shang
• Phone: +86-29-84771539
• Email: shangyl870222[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 104
• Est. completion date: December 31, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Cholangitis
• Liver Cirrhosis, Biliary
• Primary Biliary Cholangitis

Intervention

Drug:
• Fenofibrate 200mg
Fenofibrate 200mg/day
• Placebo
1 tablet/ day
• UDCA
UDCA 13-15mg/kg/day

Locations

Country	Name	City	State
China	Xijing Hospital	Xi'an	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
Xijing Hospital of Digestive Diseases

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with biochemical response	The normalisation of Alkaline Phosphatase	48 weeks
Secondary	Percentage of patients having biochemical response	The normalisation of Alkaline Phosphatase at 4, 12, 24, and 36 weeks.	4, 12, 24 and 36weeks
Secondary	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
Secondary	Percentage of patients having biological or clinical adverse events	Increase of creatinine	4, 12, 24, 36, and 48 weeks
Secondary	Percentage of patients having biological or clinical adverse events	Increase Blood urea nitrogen	4, 12, 24, 36, and 48 weeks
Secondary	Percentage of patients having biological or clinical adverse events	Increase of creatine kinase	4, 12, 24, 36, and 48 weeks
Secondary	Percentage of patients having biological or clinical adverse events	Increase ALT and AST.	4, 12, 24, 36, and 48 weeks
Secondary	Survival without transplantation and hepatic impairment	Occurrence of ascites, variceal bleeding, hepatic encephalopathy, liver-transplantation, or death.	48 weeks