Fenofibrate treatment for patients with compensated cirrhosis and primary biliary cholangitis

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

This study is testing if fenofibrate can help people with compensated cirrhosis caused by primary biliary cholangitis feel better when added to their current treatment.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 104 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Xijing Hospital of Digestive Diseases (other)
• Locations: 12 sites (Beijing, Beijing Municipality and 11 other locations)
• Trial ID: NCT05749822 on ClinicalTrials.gov

What this trial studies

This clinical trial is a multi-center, randomized, placebo-controlled study designed to evaluate the efficacy and safety of fenofibrate in patients with compensated cirrhosis due to primary biliary cholangitis (PBC) who have not responded adequately to UDCA. Participants will receive either fenofibrate or a placebo daily for 12 months, alongside UDCA treatment. The primary outcome will focus on changes in serum alkaline phosphatase levels, while also monitoring safety and tolerability throughout the study period.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-75 with a confirmed diagnosis of compensated cirrhosis and primary biliary cholangitis who have not adequately responded to UDCA.

Not a fit: Patients with decompensated cirrhosis or those who do not meet the specific diagnostic criteria for PBC may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve liver function and quality of life for patients with PBC and compensated cirrhosis.

How similar studies have performed: While there have been studies on UDCA for PBC, the use of fenofibrate in this specific patient population is novel and has not been extensively tested.

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

Where this trial is running

Beijing, Beijing Municipality and 11 other locations

• Peking Union Medical College Hospital — Beijing, Beijing Municipality, China (RECRUITING)
• Sun Yat-sen Memorial Hospital — Guangzhou, Guangdong, China (NOT_YET_RECRUITING)
• Henan Provincial People's Hospital — Zhengzhou, Henan, China (RECRUITING)
• Xiangya Hospital Central South University — Changsha, Hunan, China (RECRUITING)
• Jiangsu Province Hospital — Nanjing, Jiangsu, China (RECRUITING)
• The First Hospital of China Medical University — Shenyang, Liaoning, China (RECRUITING)
• Xijing Hospital — Xi'an, Shaanxi, China (RECRUITING)
• Yan'an University Affiliated Hospital — Yan’an, Shaanxi, China (RECRUITING)
• Sichuan Provincial People's Hospital — Chengdu, Sichuan, China (RECRUITING)
• Tianjin Third Central Hospital — Tianjin, Tianjin Municipality, China (RECRUITING)
• The Second Affiliated Hospital of Kunming Medical University — Kunming, Yunnan, China (RECRUITING)
• Tianjin Medical University General Hospital — Tianjin, China (RECRUITING)

Study contacts

• Principal investigator: Ying Han — Xijing Hospital, Air Force Military Medical Universit
• Study coordinator: Yulong Shang

Conditions: Primary Biliary Cholangitis