A Study of Elafibranor in Adults With Primary Biliary Cholangitis and Inadequate Response or Intolerance to Ursodeoxycholic Acid.

Last updated: March 31, 2025
Sponsor: Ipsen
Overall Status: Active - Recruiting

Phase

3

Condition

Gall Bladder Disorders

Primary Biliary Cholangitis

Liver Disease

Treatment

Placebo

Elafibranor

Clinical Study ID

NCT06383403
CLIN-60190-463
2024-510695-20-00
  • Ages > 18
  • All Genders

Study Summary

The participants in this study will have confirmed PBC with inadequate response or intolerance to Ursodeoxycholic acid (UDCA), which is a medication used in the management and treatment of cholestatic liver disease.

Primary biliary cholangitis is a slowly progressive disease characterised by damage of the bile ducts in the liver, leading to a build-up of bile acids which causes further damage. The liver damage in PBC may lead to scarring (cirrhosis). PBC may also be associated with multiple symptoms.

Many patients with PBC may require a liver transplant or may die if the disease progresses and a liver transplant is not done. This study will compare a daily dose of elafibranor (the study drug) to a daily dose of placebo (a dummy treatment).

The main aim of this study is to determine if elafibranor is better than placebo in reducing ALP levels to a normal value. High ALP levels in the blood can indicate liver disease.

There will be three periods in this study: A screening period (up to 8 weeks) to assess whether the participant can take part; a treatment period (up to 52 weeks) where eligible participants will be grouped as per their blood ALP levels and randomly assigned to either receive elafibranor or placebo, and a follow-up period (4 weeks) where participants' health will be monitored.

Participants will be twice as likely to receive elafibranor than placebo (2:1 ratio).

Participants will undergo blood sampling, urine collections, physical examinations, clinical evaluations, electrocardiograms (ECG: recording of the electrical activity of heart), ultrasound examinations (a noninvasive test that passes a probe over skin to look at the bladder, urinary tract, and liver), and Fibroscan® examinations (a noninvasive test that passes a probe on skin to measure stiffness of the liver).

They will also be asked to fill in questionnaires. Each participant will be in this study for up to 64 weeks (15 months).

Eligibility Criteria

Inclusion

Inclusion Criteria

  • Male or female participants age ≥18 years of age.

  • Participants with a historical diagnosis of PBC as demonstrated by the presence of ≥2 of the following three historical diagnostic criteria:

  • i. History of elevated ALP levels for ≥6 months prior to the first screening visit (SV1).

  • ii. Positive Antimitochondrial antibody (AMA) titres (≥1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay) or positive PBC-specific antinuclear antibodies.

  • iii. Liver biopsy consistent with PBC.

  • ALP >1 × ULN and <1.67 × ULN.

  • Participants taking UDCA should have been on this medication for at least 6 months and at a stable dose for ≥3 months. Participants who are intolerant to UDCA should have taken the last dose of UDCA ≥3 months prior.

  • Participants taking medications for management of pruritus must be on a stable dose for ≥3 months.

  • Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

  • (a) Male participants must agree that, if their partner is at risk of becoming pregnant, they will use an effective method of contraception. The participant must agree to use contraception during the whole period of the study and for 30 days after the last dose of study intervention.
  • Capable of giving signed informed consent

Exclusion Criteria

  • History or presence of other concomitant liver diseases.

  • Participants with known cirrhosis who have a Child-Pugh B or C score. Participants with cirrhosis with Child-Pugh A score are allowed.

  • History of liver transplantation.

  • History or presence of clinically significant hepatic decompensation.

  • Known history of human immunodeficiency virus (HIV) infection.

  • Medical conditions that may cause non-hepatic increases in ALP (e.g. Paget's disease).

  • Evidence of any other unstable or untreated clinically significant conditions that are not well controlled.

  • Medical condition with a life expectancy <2 years.

  • Known malignancy or history of malignancy within the last 2 years, except for successfully treated localised basal cell carcinoma or squamous cell carcinoma of the skin; or in-situ carcinoma of the uterine cervix.

  • History of hepatocellular carcinoma.

  • Alpha-foetoprotein (AFP) >20 ng/mL with 4-phase liver computed tomography (CT) or magnetic resonance imaging (MRI) scans suggesting presence of liver cancer.

  • Administration of the following medications is prohibited during the study, and prior to the study as per the timelines specified below:

  • i. Systemic (oral or parenteral) use within 3 months prior to SV1 of: fibrates, seladelpar, glitazones, obeticholic acid, azathioprine, cyclosporine, methotrexate, mycophenolate, or long-term systemic corticosteroids (parenteral and oral chronic administration only); potentially hepatotoxic drugs (including α-methyl-dopa, valproic acid, isoniazid or nitrofurantoin)
  • Participants with previous exposure to elafibranor.

  • Participants who are currently participating in, plan to participate in, or have participated in an investigational drug study or medical device study containing active substance within 30 days or 5 half-lives, whichever is longer.

  • Total bilirubin (TB) >2 × ULN. Participants with Gilbert's syndrome are eligible with a TB above 2 × ULN if direct bilirubin is <30% of TB.

  • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >5 × ULN.

  • Creatine phosphokinase (CPK) >2 × ULN.

  • Platelet count <75,000/µL.

  • International normalised ratio >1.3 in the absence of anticoagulant therapy.

  • Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m2.

  • Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as participants with evidence of significantly impaired kidney function or underlying kidney injury).

Other exclusions

  • For female participants: known pregnancy, or has a positive serum pregnancy test, or is breastfeeding.

  • Regular alcohol intake in excess of the recommended limit of 2 standard drinks per day for men or 1 standard drink per day for women.

  • History of alcohol abuse, or other substance abuse within 1 year prior.

  • Known hypersensitivity to the investigational product or to any of the excipients of elafibranor.

  • Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.

  • Any other condition that, in the opinion of the investigator, would interfere with study participation or completion, or would put the participant at risk, including a potential participant assessed as being at high risk of noncompliance with the study.

Study Design

Total Participants: 72
Treatment Group(s): 2
Primary Treatment: Placebo
Phase: 3
Study Start date:
July 09, 2024
Estimated Completion Date:
October 31, 2026

Connect with a study center

  • Hepato-Gastroenterologie HK, s.r.o.

    Hradec Králové,
    Czechia

    Active - Recruiting

  • Krajska Nemocnice Liberec

    Liberec,
    Czechia

    Site Not Available

  • Artroscan

    Ostrava,
    Czechia

    Active - Recruiting

  • Research Site s.r.o.

    Plzen,
    Czechia

    Active - Recruiting

  • Institute for Clinical and Experimental Medicine - IKEM

    Prague,
    Czechia

    Active - Recruiting

  • Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez

    Lille,
    France

    Active - Recruiting

  • Cic Inserm 0802 - CHU Poitiers

    Poitiers,
    France

    Active - Recruiting

  • Clinique Pasteur

    Toulouse,
    France

    Active - Recruiting

  • Hopital Paul-Brousse - APHP

    Villejuif,
    France

    Site Not Available

  • Charite Universitatsmedizin Berlin

    Berlin,
    Germany

    Site Not Available

  • DRK Kliniken Berlin Mitte

    Berlin,
    Germany

    Active - Recruiting

  • Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt

    Frankfurt,
    Germany

    Active - Recruiting

  • Universitatsklinikum Heidelberg

    Heidelberg,
    Germany

    Active - Recruiting

  • Gastroenterologsiche Studiengesellschaft Herne

    Hemer,
    Germany

    Active - Recruiting

  • Universitaet Des Saarlandes

    Homberg,
    Germany

    Active - Recruiting

  • Liver Study Centre Kiel

    Kiel,
    Germany

    Site Not Available

  • EUGASTRO GmbH

    Leipzig,
    Germany

    Active - Recruiting

  • Universitaetsklinikum Muenster

    Münster,
    Germany

    Active - Recruiting

  • Azienda Ospedaliera Universitaria Careggi Di Firenze

    Firenze,
    Italy

    Active - Recruiting

  • Ospedale Policlinico San Martino - IRCCS

    Genova,
    Italy

    Active - Recruiting

  • Azienda Ospedaliero Universitaria Modena

    Modena,
    Italy

    Site Not Available

  • Azienda Ospedaliero Universitaria Federico II di Napoli

    Naples,
    Italy

    Active - Recruiting

  • Pusan National University Hospital (PNUH)

    Naples,
    Italy

    Active - Recruiting

  • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

    Palermo,
    Italy

    Active - Recruiting

  • Azienda Ospedaliero Universitaria Pisana

    Pisa,
    Italy

    Active - Recruiting

  • IRCCS Istituto clinico humanitas - Humanitas Mirasole spa

    Rozzano,
    Italy

    Active - Recruiting

  • Korea University Ansan Hospital

    Ansan si,
    Korea, Republic of

    Active - Recruiting

  • Keimyung University Dongsan Hospital

    Daegu,
    Korea, Republic of

    Active - Recruiting

  • Kyungpook National University Hospital (KNUH)

    Daegu,
    Korea, Republic of

    Active - Recruiting

  • The Catholic University of Korea Daejeon St.Mary's Hospital

    Daejeon,
    Korea, Republic of

    Active - Recruiting

  • Pusan National University Hospital (PNUH)

    Pusan,
    Korea, Republic of

    Site Not Available

  • CHA Bundang Medical Center, CHA University

    Seongnam-si,
    Korea, Republic of

    Active - Recruiting

  • Seoul National University Bundang Hospital (SNUBH)

    Seongnam-si,
    Korea, Republic of

    Site Not Available

  • Samsung Medical Center

    Seoul,
    Korea, Republic of

    Active - Recruiting

  • Seoul National University Hospital

    Seoul,
    Korea, Republic of

    Active - Recruiting

  • Severance Hospital, Yonsei University Health System

    Seoul,
    Korea, Republic of

    Active - Recruiting

  • The Catholic University of Korea, Eunpyeong St. Mary's Hospital

    Seoul,
    Korea, Republic of

    Active - Recruiting

  • NZOZ Twoje Zdrowie EL Sp. z o.o.

    Elbląg,
    Poland

    Site Not Available

  • Krakowskie Centrum Medyczne Sp.z.o.o - FutureMeds

    Kraków,
    Poland

    Active - Recruiting

  • FutureMeds Warszawa Centrum

    Warsaw,
    Poland

    Active - Recruiting

  • CAROL DAVILA EMERGENCY UNIVERSITARY MILITARY HOSPITAL, Centrul Pentru Studiul Metabolismului, Research Metabolism Center

    Bucuresti,
    Romania

    Active - Recruiting

  • Spital Clinic Dr I Cantacuzino

    Bucuresti,
    Romania

    Active - Recruiting

  • Cluj County Clinical Emergency Hospital

    Cluj-Napoca,
    Romania

    Active - Recruiting

  • Gastromedica Srl

    Iaşi,
    Romania

    Active - Recruiting

  • Hospital Clinic i Provincial de Barcelona

    Barcelona,
    Spain

    Active - Recruiting

  • Hospital Universitario Vall d'Hebron

    Barcelona,
    Spain

    Active - Recruiting

  • Hospital General Universitario Gregorio Maranon (HGUGM)

    Madrid,
    Spain

    Active - Recruiting

  • Hospital Universitario La Paz

    Madrid,
    Spain

    Active - Recruiting

  • Hospital Universitario Puerta de Hierro de Majadahonda

    Majadahonda,
    Spain

    Active - Recruiting

  • Hospital Universitario Virgen de la Victoria

    Málaga,
    Spain

    Active - Recruiting

  • Hospital De Montecelo

    Pontevedra,
    Spain

    Site Not Available

  • Institut d Investigacio i Innovacio Parc Tauli, Hospital Universitari Parc Tauli

    Sabadell,
    Spain

    Active - Recruiting

  • Hospital Universitario Marques De Valdecilla

    Santander,
    Spain

    Site Not Available

  • Hospital Universitario Rio Hortega

    Valladolid,
    Spain

    Site Not Available

  • Hospital Universitario Miguel Servet

    Zaragoza,
    Spain

    Active - Recruiting

  • Aberdeen Royal Infirmary NHS Grampian Grampian Health Board

    Aberdeen,
    United Kingdom

    Active - Recruiting

  • Bradford Royal Infirmary - Bradford Teaching Hospitals NHS Foundation

    Bradford,
    United Kingdom

    Active - Recruiting

  • Frimley Park Hospital - Frimley Health NHS Foundation Trust

    Frimley,
    United Kingdom

    Active - Recruiting

  • Queen Elizabeth University Hospital - Greater Glasgow Health Board

    Glasgow,
    United Kingdom

    Active - Recruiting

  • Hull Royal Infirmary - Hull University Teaching Hospitals NHS Trust

    Hull,
    United Kingdom

    Active - Recruiting

  • Ambrose King Centre-Royal London Hospital-Barts Health NHS Trust

    London,
    United Kingdom

    Active - Recruiting

  • King's College Hospital

    London,
    United Kingdom

    Site Not Available

  • The Royal Free Hospital - Royal Free London NHS Foundation Trust

    London,
    United Kingdom

    Site Not Available

  • The Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital

    Newcastle Upon Tyne,
    United Kingdom

    Site Not Available

  • Queen's Medical Centre - Nottingham University Hospitals NHS Trust

    Nottingham,
    United Kingdom

    Site Not Available

  • John Radcliffe Hospital - Oxford University Hospitals NHS Foundation Trust

    Oxford,
    United Kingdom

    Site Not Available

  • Kindred Medical Institute for Clinical Trials

    Corona, California 92879
    United States

    Site Not Available

  • Southern California Research Center

    Coronado, California 92118
    United States

    Active - Recruiting

  • Topgraphy Health, Inc.

    Los Angeles, California 90005
    United States

    Active - Recruiting

  • University of California Los Angeles

    Los Angeles, California 90095
    United States

    Site Not Available

  • University of California, Davis

    Sacramento, California 95616
    United States

    Active - Recruiting

  • Stanford University Medical Center

    Stanford, California 94305
    United States

    Active - Recruiting

  • Peak Gastroenterology Associates

    Colorado Springs, Colorado 80135
    United States

    Active - Recruiting

  • Rocky Mountain Gastroenterology

    Littleton, Colorado 80120
    United States

    Active - Recruiting

  • International Center for Research

    Tampa, Florida 33614
    United States

    Active - Recruiting

  • Delta Research Partners, LLC

    West Monroe, Louisiana 71291
    United States

    Active - Recruiting

  • University of Michigan Health System

    Ann Arbor, Michigan 48109
    United States

    Active - Recruiting

  • Huron Gastroenterology Associates - Center for Digestive Care

    Ypsilanti, Michigan 48197
    United States

    Active - Recruiting

  • South Denver Gastroenterology,P.C.

    Englewood, New Jersey 80113
    United States

    Active - Recruiting

  • Southwest Gastroenterology Associates, PC (SWGA)

    Albuquerque, New Mexico 87109
    United States

    Active - Recruiting

  • Northwell Health Center for Liver Disease and Transplantation

    Manhasset, New York 11030
    United States

    Active - Recruiting

  • NYU Langone Health

    New York, New York 10016
    United States

    Active - Recruiting

  • Charlotte Gastroenterology & Hepatology, PLLC

    Charlotte, North Carolina 28277
    United States

    Active - Recruiting

  • Coastal Research Institute

    Fayetteville, North Carolina 28304
    United States

    Active - Recruiting

  • Gastroenterology Center of the Midsouth

    Cordova, Tennessee 38018
    United States

    Active - Recruiting

  • Methodist Transplant Physicians

    Dallas, Texas 75203
    United States

    Active - Recruiting

  • Liver Associates of Texas, P.A.

    Houston, Texas 77030
    United States

    Active - Recruiting

  • Gastro health & Nutrition

    Katy, Texas 77494
    United States

    Site Not Available

  • American Research Corporation

    San Antonio, Texas 78215
    United States

    Active - Recruiting

  • American Research Corporation at The Texas Liver Institute

    San Antonio, Texas 78215
    United States

    Active - Recruiting

  • University of Virginia Medical Center

    Charlottesville, Virginia 22903
    United States

    Site Not Available

  • Bon Secours Richmond Community Hospital d/b/a Bon Secours Liver Institute of Richmond

    Richmond, Virginia 23226
    United States

    Active - Recruiting

  • Velocity Liver Institute NW

    Seattle, Washington 98105
    United States

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.