Clinical trial NCT05749822: 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
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Primary Biliary Cholangitis
Lead sponsor: Xijing Hospital of Digestive Diseases
Sponsor class: OTHER
First posted: 2023-03-01
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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:

  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

Primary outcomes:
measure: Percentage of patients with biochemical response
timeFrame: 48 weeks
Secondary outcomes:
measure: Percentage of patients having biochemical response
timeFrame: 4, 12, 24 and 36weeks
measure: Assessment of the pruritus and fatigue
timeFrame: 4, 12, 24, 36, and 48 weeks
measure: Percentage of patients having biological or clinical adverse events
timeFrame: 4, 12, 24, 36, and 48 weeks
measure: Percentage of patients having biological or clinical adverse events
timeFrame: 4, 12, 24, 36, and 48 weeks
measure: Percentage of patients having biological or clinical adverse events
timeFrame: 4, 12, 24, 36, and 48 weeks
measure: Percentage of patients having biological or clinical adverse events
timeFrame: 4, 12, 24, 36, and 48 weeks
measure: Survival without transplantation and hepatic impairment
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Xi'an
country: China
facility: Xijing Hospital
state: Shaanxi
city: Yanan
country: China
facility: Yan'an University Affiliated Hospital
state: Shaanxi
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
Study officials:
affiliation: Xijing Hospital, Air Force Military Medical Universit
name: Ying Han
role: PRINCIPAL_INVESTIGATOR
References: