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BPCPhase 3BEZURSO 2NCT06443606

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 Phase 3 study testing Bezafibrate 400 mg in addition to UDCA therapy and Bezafibrate 200 mg in addition to UDCA therapy in people with BPC and Non Optimal Response to UDCA, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Primary biliary cholangitis (PBC) is a rare chronic, progressive, cholestatic liver disease that leads to cirrhosis and its life-threatening complications if undertreated. Ursodeoxycholic acid (UDCA) is the standard-of-care therapy for PBC. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
BPC, Non Optimal Response to UDCA
What is being tested?
Bezafibrate 400 mg in addition to UDCA therapy and Bezafibrate 200 mg in addition to UDCA therapy
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
108 participants
Where
1 siteFrance
Study dates
27 Mar 2025to 1 Jun 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
Show all 14Show fewer
  • 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.

Who cannot join

  • 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
Show all 32Show fewer
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

France1 site, 1 recruiting
  • Hepatology department - Hospital Saint Antoine

    Paris, 75012

    Christophe Corpechot, Doctor, + 33 (0) 1 49 28 28 36, christophe.corpechot@aphp.fr

    Recruiting

Other trials in France

About this study

Official title: 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.

Primary biliary cholangitis (PBC) is a rare chronic, progressive, cholestatic liver disease that leads to cirrhosis and its life-threatening complications if undertreated. Ursodeoxycholic acid (UDCA) is the standard-of-care therapy for PBC. However, patients with an inadequate biochemical response to UDCA according to the Paris-2 criteria are still at high-risk of poor clinical outcome. In this situation of biochemical resistance to UDCA, bezafibrate 400 mg/d given in association with UDCA has been shown to improve the symptoms, biochemical response (BEZURSO study), histologic features, and possibly long-term clinical outcome. However, it has been shown that even patients with an adequate response to UDCA but persistent elevation in biochemical markers of cholestasis or liver inflammation, including alkaline phosphatases (ALP), gamma-glutamyl transpeptidase (GGT), transaminases, or total bilirubin (i.e., non-optimal biochemical response) have still an increased risk of death or liver transplantation in the long term, thus defining the complete normalization of these markers as the new clinically-relevant target for PBC treatment. In parallel to these findings, bezafibrate 400 mg/d as a second-line therapy for PBC could be associated with potentially dose-related, muscle, kidney, or liver toxic effects, and whether bezafibrate 200 mg/d could have a better benefit/risk ratio in this disease-setting remains to be determined. Therefore, our aim is to evaluate the efficacy and safety of bezafibrate 400 mg and bezafibrate 200 mg as adjunctive treatments in PBC patients with non-optimal biochemical response to UDCA.

Read the detailed description

The study is a phase-3 multicenter, randomized, parallel-group (1:1:1), placebo-controlled trial with a 12-month, double-blind, placebo-free extension phase.

It evaluates the efficacy and safety of bezafibrate 400 mg and bezafibrate 200 mg as adjunctive treatments in patients with PBC with an non-optimal biochemical response to UDCA.

Treatments groups :

Arm 1: Bezafibrate 400 mg and Placebo of Bezafibrate 200 mg until 96 weeks in double blind.

Arm 2: Bezafibrate 200 mg and Placebo of Bezafibrate 400 mg until 96 weeks in double blind.

Arm 3: Placebo of Bezafibrate 400 mg and Placebo of Bezafibrate 200 mg until 48 weeks in double blind. Then follow-up extension phase of bezafibrate 400 mg or bezafibrate 200 mg (second randomization) until 48 weeks in double blind.

Assessement: Study visits at Inclusion, Randomisation (M0) and then every 3 months until W48 and extension until W96. In accordance with routine care, an additional follow-up is added between 108 and 120 weeks

32 sites within the French network of reference and competence centres for rare liver diseases FILFOIE will participate.

No interim analysis planned. Analysis will be performed at the end of the study after data reviewed and data base locked according to the intent to treat principle.

Being tested
Bezafibrate 400 mg in addition to UDCA therapy, Bezafibrate 200 mg in addition to UDCA therapy, Placebo in addition to UDCA therapy
Keywords
Bezafibrate, PBC, Digestive System Diseases, Ursodeoxycholic Acid
Medical subject headings
Digestive System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bezafibrate 400 mg in addition to UDCA therapyDrug

    • Bezafibrate 400 mg and Placebo of Bezafibrate 200 mg in addition to continued UDCA at minimum dose of 12 mg/kg/d.
    • Duration 96 weeks bezfibrate/ UDCA = daily oral dose.
  • Bezafibrate 200 mg in addition to UDCA therapyDrug

    • Bezafibrate 200 mg and Placebo of Bezafibrate 400 mg in addition to continued UDCA at minimum dose of 12 mg/kg/d.
    • Duration 96 weeks bezfibrate/ UDCA = daily oral dose.
  • Placebo in addition to UDCA therapyDrug

    • Placebo of Bezafibrate 400 mg and Placebo of Bezafibrate 200 mg in addition to continued UDCA at minimum dose of 12 mg/kg/d.
    • Duration 96 weeks placebo /UDCA = daily oral dose.
Study groups in NCT06443606
Study groupRoleWhat they receive
Bezafibrate 400 mg group in addition to UDCA therapyExperimentalBezafibrate 400 mg and Placebo of Bezafibrate 200 mg until 48 weeks in double blind
Receives: Drug: Bezafibrate 400 mg in addition to UDCA therapy
Bezafibrate 200 mg group in addition to UDCA therapyExperimentalBezafibrate 200 mg and Placebo of Bezafibrate 400 mg until 96 weeks in double blind.
Receives: Drug: Bezafibrate 200 mg in addition to UDCA therapy
Placebo group in addition to UDCA therapyPlacebo comparatorPlacebo of Bezafibrate 400 mg Placebo of Bezafibrate 200 mg until 48 weeks in double blind. And follow-up extension phase of bezafibrate 400 mg and bezafibrate 200 mg until 48 weeks in double blind.
Receives: Drug: Placebo in addition to UDCA therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To assess the effect of bezafibrate 200 mg and bezafibrate 400 mg versus placebo as adjunctive treatments in patients with PBC and a non-optimal response to UDCA.

    Proportion of patients with a complete biochemical response defined by normal serum levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), aminotransferases (AST, ALT), and total bilirubin at 48 weeks of treatment.

    Measured: Week 48

Secondary outcomes (11)
  1. To compare adverse effects between groups, in particular on muscle, kidney, and liver.

    Proportion of patients with serious adverse events (SAE) and/or adverse events (AE) at W48 and W96 (extension phase), including creatinine > 150 μmol/L, CPK > 10 xULN, or ALT > 5 xULN.

    Measured: Week 48 and Week 96 ( extension phase)

  2. To compare symptoms (Pruritus) between groups

    Proportion of patients with significant pruritus based on worst itch numerical rating scale (WI-NRS).

    Measured: Week 48 and Week 96 (extension phase)

  3. To compare symptoms (fatigue) between groups.

    Proportion of patients with significant fatigue at W48 and W96 based on PBC-40 questionnaire.

    Measured: Week 48 and Week 96 (extension phase)

  4. To compare quality of life (QoL) between groups.

    Changes from baseline to W48 and W96 in quality of life assessed by PBC-40.

    Measured: Week 48 and Week 96 (extension phase)

  5. Level of liver biochemical parameters between groups

    Proportion of patients with a deep biochemical response defined by normal levels of ALP, GGT, ALT, AST, and a total bilirubin ≤ 0.6 mg/dL.

    Measured: Week 48 and Week 96 (extension phase)

  6. Changes in liver stiffness by Fibroscan

    To compare changes in non-invasive markers of liver fibrosis between groups.

    Measured: Week 48 and Week 96 (extension phase)

  7. Changes in liver stiffness (Fibroscan) by ELF test.

    To compare changes in non-invasive markers of liver fibrosis between groups.

    Measured: Week 48 and Week 96 (extension phase)

  8. Changes in liver stiffness (Fibroscan) by FIB-4 score.

    To compare changes in non-invasive markers of liver fibrosis between groups.

    Measured: Week 48 and Week 96 (extension phase)

  9. Proportion of patients with advanced fibrosis or cirrhosis as diagnosed by Fibroscan

    To compare changes in non-invasive markers of liver fibrosis between groups.

    Measured: Week 48 and Week 96 (extension phase)

  10. Proportion of patients with moderately advanced or advanced disease as diagnosed by the Rotterdam criteria

    To compare changes in non-invasive markers of liver fibrosis between groups.

    Measured: Week 48 and Week 96 (extension phase)

  11. To compare occurrence of clinical events including death, LT, or liver complications between groups.

    Occurrence of all-cause and liver-related deaths, LT, referral for LT, ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, unscheduled hospitalization, development of any new comorbidities or significant worsening of preexisting ones at W48 and W96.

    Measured: Week 48 and Week 96 (extension phase)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jun 2024
  2. Study start27 Mar 2025
  3. Primary completion30 Dec 2027 (estimated)
  4. Study completion1 Jun 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
108 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06443606
Sponsor's protocol ID
APHP220822
Acronym
BEZURSO 2
Status last verified
Aug 2025
First submitted
21 Feb 2024
Last updated
27 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bezafibrate 400 mg in addition to UDCA therapy and Bezafibrate 200 mg in addition to UDCA therapy in people with BPC and Non Optimal Response to UDCA, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Christophe Corpechot, MD (+ 33 (0) 1 49 28 28 36, christophe.corpechot@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To assess the effect of bezafibrate 200 mg and bezafibrate 400 mg versus placebo as adjunctive treatments in patients with PBC and a non-optimal response to UDCA. (time frame: Week 48). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2025.

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