Combining fenofibrate with ursodeoxycholic acid for treating primary biliary cholangitis

A Prospective, Multi-center, Randomized, Double-blind, Placebo-controlled Study: Fenofibrate Combined With Ursodeoxycholic Acid in Subjects With Primary Biliary Cholangitis and an Inadequate Response to Ursodeoxycholic Acid

This study is testing if adding fenofibrate to the usual treatment with ursodeoxycholic acid can help people with primary biliary cholangitis who aren't getting better with just ursodeoxycholic acid.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Xijing Hospital of Digestive Diseases (Academic / other)
• Locations: 7 sites (Lanzhou, Gansu and 6 other locations)
• Trial ID: NCT05751967 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of fenofibrate in combination with ursodeoxycholic acid (UDCA) for patients with primary biliary cholangitis (PBC) who do not respond adequately to UDCA alone. The study employs a multi-center, randomized, placebo-controlled design, administering either fenofibrate or a placebo alongside UDCA for 48 months. The primary goal is to achieve complete normalization of alkaline phosphatase (ALP) and total bilirubin (TBIL) levels, while secondary outcomes include monitoring adverse events and assessing liver health over time. The trial also aims to refine criteria for identifying patients who may benefit from additional therapies earlier in their treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with a diagnosis of primary biliary cholangitis and an inadequate response to UDCA as defined by specific biochemical criteria.

Not a fit: Patients with other liver diseases or those who are allergic to fenofibrate or ursodeoxycholic acid may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective treatment option for patients with primary biliary cholangitis who do not respond to standard therapy.

How similar studies have performed: While the combination of fenofibrate and UDCA has been explored, this specific approach using the Xi'an criteria for early identification of non-responders is novel.

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.
* Incomplete response to UDCA defined by Xi'an criteria (ALP \>2.5× ULN, AST\>2×ULN or TBIL\>1×ULN) after UDCA treatment for 4-6 weeks with at least one abnormal test in ALP or TBIL.

Exclusion Criteria:

* History or presence of other concomitant liver diseases.
* ALT/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 the quality of the clinical study, as judged by the Investigator.

Where this trial is running

Lanzhou, Gansu and 6 other locations

• The second hospital of Lanzhou University — Lanzhou, Gansu, China (Recruiting)
• Sun Yat-sen Memorial Hospital — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Nanjing Drum Tower Hospital — Nanjing, Jiangsu, China (Recruiting)
• The First Hospital of China Medical University — Shenyang, Liaoning, China (Recruiting)
• Ying han — Xi'an, Shaanxi, China (Recruiting)
• Sichuan Provincial People's Hospital, — Chengdu, Sichuan, China (Recruiting)
• Tianjin Medical University General Hospital — Tianjin, China (Recruiting)

Study contacts

• Principal investigator: Ying Han, Doctor — The First Affiliated Hospital of Air Force Medicial University
• Study coordinator: Yulong Shang

Conditions Primary Biliary Cholangitis