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 - BEZURSO 2

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

27 Mar 2025 → ongoing

Decision date (initial)

2024-09-03

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Ministry of Health

External identifiers

EU CT number

2023-504086-23-00

ClinicalTrials.gov

NCT06443606

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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.

Secondary objectives 6

1. To compare between groups:
2. 1. Symptoms (pruritus, fatigue) and quality of life (QoL).
3. 2. Changes in standard liver function tests
4. 3. Changes in noninvasive markers of liver fibrosis
5. 4. Changes in non-invasive markers of liver fibrosisOccurrence of clinical events including death, liver transplantation (LT), or liver complications
6. 5. Safety, in particular on muscle, kidney, and liver

Conditions and MedDRA coding

Subjects with PBC with a non-optimal response to UDCA.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Age ≥ 18 and < 80 years
2. 2. Diagnosis of PBC based on at least 2 of the following criteria (EASL clinical practice guidelines 2017:
3. a. Elevated ALP level
4. b. 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
5. c. Records of histologic features suggestive of, or compatible with PBC
6. 3. UDCA therapy for the past 12 months (stable dose ≥ 12 mg/kg/d for ≥ 3 months prior to inclusion)
7. 4. Biochemical evidence of non-optimal response to UCDA (i.e. ALP > 1.0 xULN, or GGT > 3.0 xULN, or ALT or AST > 1.0 xULN, or total and conjugated bilirubin > 1.0 xULN) between 6 months and 2 weeks before inclusion visit. If total bilirubin is within the normal range, measurement of conjugated bilirubin is not mandatory.
8. 5. Women of child-bearing potential (WOCBP), i.e., fertile, following menarche and until becoming post-menopaused unless permanently sterile, who are sexually active have to apply an effective method of birth control*, throughout the study period and for 90 days following the last dose of study treatment. *the list of acceptable method of contraception is in addenda 18.1
9. 6. Affiliation to a social security system (AME excepted)
10. 7. Signed informed consent

Exclusion criteria 21

1. 1. 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%; in the last 6 months; Child-Pugh score B or C; MELD score ≥ 14; History ≤ 24 months or presence of cirrhotic decompensation; Patients on the waiting list for LT
2. 2. GFR estimated by CKI-EPI equation < 60 mL/min in the last 6 months
3. 3. CPK > 5.0 xULN in the last 6 months
4. 4. AST or ALT > 3.0 xULN in the last 6 months
5. 5. History of LT
6. 6. Features of autoimmune hepatitis (AIH) overlap syndrome (either past or newly diagnosed during follow up)
7. 7. Any other chronic hepatic comorbidities (HIV, HCV, HBV, NASH, alcoholic liver disease, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, celiac disease)
8. 8. Untreated hypo or hyperthyroidism (Hashimoto or Graves autoimmune thyroiditis)
9. 9. Conditions that may cause non-hepatic increases in ALP (Paget’s disease, osteodystrophy, hyperparathyroidism, dysglobulinemia)
10. 10. Gilbert’s syndrome or chronic hemolysis (hyperbilirubinemia with an unconjugated to total bilirubin ratio ≥ 75%)
11. 11. History of or established or suspected hepatocellular carcinoma
12. 12. History of malignancy diagnosed or treated within 2
13. 13. Any severe comorbidity that may reduce life expectancy ≤ 2 years
14. 14. Pregnancy or lactating
15. 15. Known intolerance to bezafibrate
16. 16. Known hypersensitivity to bezafibrate, any of the components of Befizal© or other fibrates
17. 17. Known photosensitivity reactions or photoallergic reactions to fibrates
18. 18. Patient with congenital galactosemia, glucose malabsorption, or lactase deficiency because of presence of lactose in LP tablets of bezafibrate
19. 19. Participation in any other interventional study in the past 6 months (RIPH1, clinical investigation or clinical trial)
20. 20. 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.
21. 21. Use of statins in the month before inclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • 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.

Secondary endpoints 3

1. 1. Changes from baseline to W48 in itch intensity mean of the last 24h assessed by NRS as recommended by IFSI SIG / EADV Task Force Pruritus.
2. 2. Proportion of patients with normal levels of ALP at W48.
3. 3. Changes from baseline to W48 in LSM assessed by Fibroscan.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Christophe CORPECHOT

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Riad BAAMEUR

Locations

1 EU/EEA country · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications