Fenofibrate versus UDCA for first-line treatment of primary biliary cholangitis

A Multicenter, Randomized, Double-Blind, Double-Dummy, Active-Controlled Clinical Trial of Fenofibrate in Treatment-Naïve Patients With Primary Biliary Cholangitis

This study will test whether fenofibrate works better than the standard medicine UDCA for adults with newly diagnosed primary biliary cholangitis who have not been treated before.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 132 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Xijing Hospital of Digestive Diseases (Academic / other)
• Drugs / interventions: methotrexate
• Locations: 1 site (Xi'an, Shaanxi)
• Trial ID: NCT07296458 on ClinicalTrials.gov

What this trial studies

Adults with untreated primary biliary cholangitis will be randomly assigned, in a double-blind manner, to receive either fenofibrate plus a UDCA placebo or UDCA plus a fenofibrate placebo for 12 months. The main laboratory outcome is improvement in alkaline phosphatase (ALP) as a marker of liver function, and safety and adverse events will be tracked throughout. Participants will attend five clinic visits at months 1, 3, 6, 9, and 12 for exams and blood tests. People with other liver diseases, recent use of UDCA or fenofibrate, or pregnancy are excluded.

Who should consider this trial

Good fit: Adults aged 18 to under 75 with a confirmed diagnosis of primary biliary cholangitis, treatment-naive for UDCA and fenofibrate, and an elevated ALP are the intended participants.

Not a fit: People with other concurrent liver diseases, women who are pregnant or breastfeeding, those who used UDCA or fenofibrate in the prior 6 months, or those with contraindications to the drugs are unlikely to benefit from joining this study.

Why it matters

Potential benefit: If successful, fenofibrate could provide a better first-line option that more quickly normalizes liver tests and reduces disease activity for people with PBC.

How similar studies have performed: Previous studies have shown that fibrates (including bezafibrate and smaller fenofibrate studies) can improve liver biochemistry when added to UDCA in refractory PBC, but head-to-head use of fenofibrate as a first-line alternative to UDCA is largely untested.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily join the group and be able to understand and sign the informed consent form;
2. Age: 18 years old or above and below 75 years old;
3. The diagnosis of primary biliary cholangitis follows the AASLD international diagnostic and treatment guidelines (meeting two of the following three criteria: positive AMA or gp210, sp100; elevated serum ALP; pathological manifestations of non-suppurative cholangitis and interlobular bile duct destruction);
4. The patient did not receive UDCA and fenofibrate treatment in the 6 months before enrollment, and ALP was greater than the upper limit of normal (ULN).

Exclusion Criteria:

1. Combined liver diseases caused by other factors: including viral hepatitis, chronic alcoholic hepatitis, steatohepatitis, drug-induced hepatitis, autoimmune hepatitis, primary sclerosing cholangitis, etc;
2. Pregnant women, lactating women, or those who plan to give birth during the study period;
3. Individuals who are allergic to fenofibrate or ursodeoxycholic acid;
4. At the time of diagnosis or in the past, there have been variceal bleeding, hepatic encephalopathy, ascites, spontaneous bacterial peritonitis, hepatocellular carcinoma, and hepatorenal syndrome;
5. Individuals with a history of severe diseases or functional failures in the heart, cerebrovascular system, kidneys, respiratory system, as well as mental illnesses (including those caused by alcohol and drug abuse);
6. Transaminase greater than 5×ULN, or total bilirubin greater than 3×ULN;
7. Creatinine level greater than 1.5×ULN;
8. Glomerular filtration rate (GFR) ≤ 45 mL/min/1.73 m2;
9. International normalized ratio (INR) ≥ 1.5 (for patients undergoing anticoagulant therapy, an INR value within the therapeutic target range is sufficient);
10. Subjects who have received treatment with obeticholic acid and other fibrates (such as gemfibrozil, bezafibrate, pemafibrate, Elafibranor, Seladelpar, Lanifibranor, Saroglitizar, etc.) within the previous 6 weeks prior to screening;
11. Screening for individuals who have taken colchicine, methotrexate, azathioprine, or undergone systemic hormone therapy for more than 2 weeks within the previous 2 months;
12. Is currently undergoing treatment with immunosuppressants (such as cyclosporine, tacrolimus, and related biologics);
13. Plan to receive organ transplantation or have already undergone organ transplantation;
14. Clear history of HIV infection or HIV antibody positive during the screening period;
15. Screen for individuals with a clear history of malignant tumor or anti-tumor treatment within the previous 2 years;
16. Other situations that researchers judge as unsuitable for enrollment.

Where this trial is running

Xi'an, Shaanxi

• Xijing Hospital — Xi'an, Shaanxi, China (Recruiting)

Conditions Primary Biliary Cholangitis