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Fenofibrate for Compensated Cirrhosis Patients With Primary Biliary Cholangitis

Primary Purpose

Primary Biliary Cholangitis

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Fenofibrate 200mg
Placebo
UDCA
Sponsored by
Xijing Hospital of Digestive Diseases
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Biliary Cholangitis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Xijing HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo-UDCA

Fenofibrate-UDCA

Arm Description

1 tablet/ day and UDCA 13-15mg/kg/day for 12 months

Fenofibrate 200 mg/day and UDCA 13-15mg/kg/day for 12 months

Outcomes

Primary Outcome Measures

Percentage of patients with biochemical response
The normalisation of Alkaline Phosphatase

Secondary Outcome Measures

Percentage of patients having biochemical response
The normalisation of Alkaline Phosphatase at 4, 12, 24, and 36 weeks.
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)
Percentage of patients having biological or clinical adverse events
Increase of creatinine
Percentage of patients having biological or clinical adverse events
Increase Blood urea nitrogen
Percentage of patients having biological or clinical adverse events
Increase of creatine kinase
Percentage of patients having biological or clinical adverse events
Increase ALT and AST.
Survival without transplantation and hepatic impairment
Occurrence of ascites, variceal bleeding, hepatic encephalopathy, liver-transplantation, or death.

Full Information

First Posted
December 29, 2022
Last Updated
March 3, 2023
Sponsor
Xijing Hospital of Digestive Diseases
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1. Study Identification

Unique Protocol Identification Number
NCT05749822
Brief Title
Fenofibrate for Compensated Cirrhosis Patients With Primary Biliary Cholangitis
Official Title
Fenofibrate Combined With Ursodeoxycholic Acid in Compensated Cirrhosis Patients With Primary Biliary Cholangitis Who Had an Inadequate Response to Ursodeoxycholic Acid
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 17, 2023 (Actual)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Xijing Hospital of Digestive Diseases

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Biliary Cholangitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
104 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo-UDCA
Arm Type
Placebo Comparator
Arm Description
1 tablet/ day and UDCA 13-15mg/kg/day for 12 months
Arm Title
Fenofibrate-UDCA
Arm Type
Experimental
Arm Description
Fenofibrate 200 mg/day and UDCA 13-15mg/kg/day for 12 months
Intervention Type
Drug
Intervention Name(s)
Fenofibrate 200mg
Intervention Description
Fenofibrate 200mg/day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
1 tablet/ day
Intervention Type
Drug
Intervention Name(s)
UDCA
Intervention Description
UDCA 13-15mg/kg/day
Primary Outcome Measure Information:
Title
Percentage of patients with biochemical response
Description
The normalisation of Alkaline Phosphatase
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Percentage of patients having biochemical response
Description
The normalisation of Alkaline Phosphatase at 4, 12, 24, and 36 weeks.
Time Frame
4, 12, 24 and 36weeks
Title
Assessment of the pruritus and fatigue
Description
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)
Time Frame
4, 12, 24, 36, and 48 weeks
Title
Percentage of patients having biological or clinical adverse events
Description
Increase of creatinine
Time Frame
4, 12, 24, 36, and 48 weeks
Title
Percentage of patients having biological or clinical adverse events
Description
Increase Blood urea nitrogen
Time Frame
4, 12, 24, 36, and 48 weeks
Title
Percentage of patients having biological or clinical adverse events
Description
Increase of creatine kinase
Time Frame
4, 12, 24, 36, and 48 weeks
Title
Percentage of patients having biological or clinical adverse events
Description
Increase ALT and AST.
Time Frame
4, 12, 24, 36, and 48 weeks
Title
Survival without transplantation and hepatic impairment
Description
Occurrence of ascites, variceal bleeding, hepatic encephalopathy, liver-transplantation, or death.
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yulong Shang
Phone
+86-29-84771539
Email
shangyl870222@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Ying Han
Phone
+86-29-84771539
Email
hanying1@fmmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ying Han
Organizational Affiliation
Xijing Hospital, Air Force Military Medical Universit
Official's Role
Principal Investigator
Facility Information:
Facility Name
Xijing Hospital
City
Xi'an
State/Province
Shaanxi
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ying Han

12. IPD Sharing Statement

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Fenofibrate for Compensated Cirrhosis Patients With Primary Biliary Cholangitis

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