Adding bezafibrate (400 mg or 200 mg) to UDCA for people with primary biliary cholangitis who have a non‑optimal lab response
Efficacy and Safety of Bezafibrate 400 mg and Bezafibrate 200 mg as Adjunctive Treatments in Patients With Primary Biliary Cholangitis and Non-optimal Biochemical Response to Ursodeoxycholic Acid Therapy: a 12-month, Double-blind, Randomized, Placebo-controlled Trial With a 12-month, Double-blind, Placebo-free Extension Phase.
This trial will test whether adding bezafibrate (400 mg or 200 mg) to standard UDCA helps adults with primary biliary cholangitis who still have abnormal liver blood tests.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 108 (estimated) |
| Ages | 18 Years to 80 Years |
| Sex | All |
| Sponsor | Assistance Publique - Hôpitaux de Paris Academic / other |
| Drugs / interventions | methotrexate |
| Locations | 1 site (Paris) |
| Trial ID | NCT06443606 on ClinicalTrials.gov |
What this trial studies
This phase 3, randomized, double‑blind, placebo‑controlled, parallel‑group trial compares bezafibrate 400 mg, bezafibrate 200 mg, and placebo added to standard UDCA in adults with PBC who have a non‑optimal biochemical response to UDCA. Participants are randomized 1:1:1 and followed with visits every three months to week 48, with a double‑blind extension phase continuing to week 96 for most arms. The primary analysis will use an intent‑to‑treat approach and no interim analyses are planned. The multicenter trial is conducted at 32 sites within the French FILFOIE network.
Who should consider this trial
Good fit: Adults aged 18–79 with confirmed PBC who have been on a stable UDCA dose for at least 12 months and have persistent elevations in ALP, GGT, transaminases, or bilirubin despite treatment.
Not a fit: Patients who already have an optimal biochemical response to UDCA, have decompensated liver disease, or who cannot take fibrates due to contraindications are unlikely to benefit from this intervention.
Why it matters
Potential benefit: If successful, adding bezafibrate to UDCA may normalize liver blood tests, relieve symptoms, and reduce the risk of progression to cirrhosis for patients with PBC who do not fully respond to UDCA.
How similar studies have performed: Previous studies, including the BEZURSO trial, showed that bezafibrate 400 mg added to UDCA improved biochemical responses, symptoms, and histology, providing supportive evidence for this phase 3 trial.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age ≥ 18 and \< 80 years * Diagnosis of PBC based on at least 2 of the following criteria (EASL clinical practice guidelines 2017): * Elevated ALP level * Presence of antimitochondrial antibody (immunofluorescence titer ≥ 1:40 or positive antigen-specific test), specific antinuclear immunofluorescence (nuclear dots or perinuclear rims) or positive antigen-specific test for anti-gp210 or anti-Sp100 antibodies * Records of histologic features suggestive of, or compatible with PBC * UDCA therapy for the past 12 months (stable dose ≥ 12 mg/kg/d for ≥ 3 months prior to inclusion). * Non-optimal response to UDCA defined by at least one of the following criteria (ratios of absolute values to ULN rounded to the first decimal digit) observed at least 2 times at ≥ 4 weeks interval in the past 3 months, including at the inclusion visit assessment: * ALP \> 1.0 xULN * GGT \> 3.0 xULN * ALT or AST \> 1.0 xULN * Total and conjugated bilirubin \> 1.0 xULN * Women of childbearing potential must use at least one barrier contraceptive during the study and for at least 90 days after the last dose. * Affiliation to a social security system (AME excepted). * Signed informed consent. Exclusion Criteria: * Any of the following signs of advanced chronic liver disease: * Total bilirubin \> 2.0 xULN * Serum albumin \< 32 g/l * Platelet count \< 100,000/mm3 * INR \> 1.3 or prothrombin index \< 60% * Child-Pugh score B or C * MELD score ≥ 14 * History ≤ 24 months or presence of cirrhotic decompensation * Patients on the waiting list for LT * GFR estimated by CKI-EPI equation \< 60 mL/min * CPK \> 5.0 xULN * AST or ALT \> 3.0 xULN * History of LT * Autoimmune hepatitis (AIH) overlap syndrome defined by at least 2 of the following 3 criteria including the histologic one: * ALT \> 5.0 xULN * IgG \> 20 g/l or presence of anti-smooth muscle or anti-SLA antibodies * Histologic features characteristic of, or compatible with AIH * Any other chronic hepatic comorbidities (HCV, HBV, NASH, alcoholic liver disease, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, celiac disease) * Untreated hypo or hyperthyroidism (Hashimoto or Graves autoimmune thyroiditis) * Conditions that may cause non-hepatic increases in ALP (Paget's disease, osteodystrophy, hyperparathyroidism, dysglobulinemia) * Gilbert's syndrome or chronic hemolysis (hyperbilirubinemia with an unconjugated to total bilirubin ratio ≥ 75%) * History of or established or suspected hepatocellular carcinoma * History of malignancy diagnosed or treated within 2 years (recent localized treatment of squamous or non-invasive basal skin cancers is permitted) * Any severe comorbidity that may reduce life expectancy ≤ 2 years * Pregnancy or lactating * Known intolerance to bezafibrate * Known hypersensitivity to bezafibrate, any of the components of Befizal© or other fibrates * Known photosensitivity reactions or photoallergy reactions to fibrates * Patient with congenital galactosemia, glucose malabsorption, or lactase deficiency because of presence of lactose in LP tablets of bezafibrate * Participation in any other interventional study in the past 6 months * Any of the following medications used in the past 3 months before inclusion: bezafibrate, fenofibrate, ciprofibrate, gemfibrozil, obeticholic acid, budesonide, any other systemic corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, sirolimus, everolimus, methotrexate. * Use of statins in the month before inclusion
Where this trial is running
Paris
- Hepatology department - Hospital Saint Antoine — Paris, France (Recruiting)
Study contacts
- Principal investigator: Christophe Corpechot, MD — Assistance Publique - Hôpitaux de Paris
- Study coordinator: Christophe Corpechot, MD
- Email: christophe.corpechot@aphp.fr
- Phone: + 33 (0) 1 49 28 28 36
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.