FIREFLY Trial: Fenofibrate Intervention---Randomized Evaluation in First-Line PBC Therapy

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

The goal of this clinical trial is to learn if the drug Fenofibrate works to treat adults with a liver disease called Primary Biliary Cholangitis (PBC) who have not received previous treatment. It will also learn about the safety of Fenofibrate. The main questions it aims to answer are:

Is Fenofibrate better at helping the liver return to normal function (measured by a blood test called ALP) than the standard medication, Ursodeoxycholic What kind of medical problems do participants have when taking Fenofibrate compared to those taking UDCA?

Researchers will compare Fenofibrate to the active drug UDCA (the current standard treatment) to see which one works better.**

Participants will:

Be randomly assigned to take either Fenofibrate plus a UDCA placebo, or UDCA plus a Fenofibrate placebo, every day for 12 months. (Neither they nor their doctor will know which group they are in.) Visit the clinic 5 times over the year (at 1, 3, 6, 9, and 12 months) for check-ups, blood tests, and questionnaires.

Undergo a special scan (like FibroScan) to measure liver stiffness at some visits.

Be encouraged to have a liver biopsy at the start and end of the study to provide detailed information about liver health (this is optional).

Study Overview

• Status: Recruiting
• Conditions: Primary Biliary Cholangitis (PBC)
• Intervention / Treatment: Drug: Fenofibrate; Drug: UDCA (Ursodeoxycholic acid)

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Xijing Hospital
      • Contact: Liu; Phone Number: +862984771539; Email: liuyansheng506@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: UDCA	Drug: UDCA (Ursodeoxycholic acid); UDCA13-15mg/kg/day+placebo
Experimental: Fenofibrate	Drug: Fenofibrate; Fenofibrate 200mg+placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Normal ALP level	at 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with both ALP and total bilirubin normalisation		12 months
Percentage of participants with ALP normalization		1, 3, 6, and 9 months of treatment
Absolute and relative changes in ALP compared to baseline		1, 3, 6, 9, and 12 months of treatment
Changes in ALT compared to baseline		1, 3, 6, 9, and 12 months of treatment
Changes in AST compared to baseline		1, 3, 6, 9, and 12 months of treatment
Changes in GGT compared to baseline		1, 3, 6, 9, and 12 months of treatment
Changes in TB compared to baseline		1, 3, 6, 9, and 12 months of treatment
Changes in itch NRS compared to baseline		1, 3, 6, 9, and 12 months of treatment
Changes in liver stiffness compared to baseline	FibroScan was used to detect the liver stiffness , and the stiffness values before and after treatment were compared	1, 3, 6, 9, and 12 months of treatment
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0		From enrollment to the end of treatment at 12 months

Collaborators and Investigators

• Sponsor: Xijing Hospital of Digestive Diseases

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: December 8, 2025
• First Posted (Estimated): December 22, 2025

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Bile Duct Diseases; Fibrosis; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Pathological Conditions, Signs and Symptoms; Liver Cirrhosis, Biliary; Organic Chemicals; Ethers; Hydrocarbons; Hydrocarbons, Cyclic; Acids, Acyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Phenols; Benzene Derivatives; Butyrates; Phenyl Ethers; Ketones; Fibric Acids; Isobutyrates; Benzophenones; Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Cholanes; Ursodeoxycholic Acid; Fenofibrate
• Other Study ID Numbers: KY-20252505

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No