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

NCT06383403 | Active Not Recruiting Phase 3 FDA Drug

• 2 other identifiers: CLIN-60190-4632024-510695-20-00
• Study Type: interventional
• Target: 69
• Locations: 10 countries
• Sites: 60

Brief 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).

Conditions

Primary Biliary Cholangitis

Outcome Measures

Primary Outcomes (1)

• Percentage of participants with normalisation of Alkaline Phosphate (ALP) Levels

  At Week 52

Secondary Outcomes (22)

• Percentage of participants with normalisation of ALP Levels

  From baseline to Week 4, Week 12, Week 24 and Week 36

• Change from baseline in ALP levels

  From baseline to Week 4, Week 12, Week 24, Week 36 and Week 52

• Percentage of participants with normalisation of ALP Levels and ≥15% decrease from Baseline

  From baseline to Week 4, Week 12, Week 24, Week 36 and Week 52

• Percentage of participants with ≥40% decrease from Baseline in ALP Levels

  From baseline to Week 4, Week 12, Week 24, Week 36 and Week 52

• Percentage of participants with ALP <0.5 × Upper Limit of Normal (ULN)

  At Week 4, Week 12, Week 24, Week 36 and Week 52

Study Arms (2)

Elafibranor 80 mg

EXPERIMENTAL

Participants will take 1 tablet of elafibranor 80 mg per day orally before breakfast with a glass of water at approximately the same time each morning.

Drug: Elafibranor

Placebo

PLACEBO COMPARATOR

Participants will take 1 placebo tablet per day orally before breakfast with a glass of water at approximately the same time each morning.

Other: Placebo

Interventions

Elafibranor DRUG

Round and orange film coated tablet of 80 mg.

Also known as: IPN60190

Elafibranor 80 mg

Placebo OTHER

Round and orange film coated tablet of placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ipsen: lead

Study Sites (60)

Southern California Research Center

Coronado, California, 92118, United States

Location

Topgraphy Health, Inc.

Los Angeles, California, 90005, United States

Location

University of California, Davis

Sacramento, California, 95616, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Peak Gastroenterology Associates

Colorado Springs, Colorado, 80135, United States

Location

Rocky Mountain Gastroenterology

Littleton, Colorado, 80120, United States

Location

International Center for Research

Tampa, Florida, 33614, United States

Location

Delta Research Partners, LLC

West Monroe, Louisiana, 71291, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Huron Gastroenterology Associates - Center for Digestive Care

Ypsilanti, Michigan, 48197, United States

Location

South Denver Gastroenterology,P.C.

Englewood, New Jersey, 80113, United States

Location

Southwest Gastroenterology Associates, PC (SWGA)

Albuquerque, New Mexico, 87109, United States

Location

Northwell Health Center for Liver Disease and Transplantation

Manhasset, New York, 11030, United States

Location

Charlotte Gastroenterology & Hepatology, PLLC

Charlotte, North Carolina, 28277, United States

Location

Coastal Research Institute

Fayetteville, North Carolina, 28304, United States

Location

Gastroenterology Center of the Midsouth

Cordova, Tennessee, 38018, United States

Location

Methodist Transplant Physicians

Dallas, Texas, 75203, United States

Location

American Research Corporation at The Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

American Research Corporation

San Antonio, Texas, 78215, United States

Location

Velocity Liver Institute NW

Seattle, Washington, 98105, United States

Location

Hepato-Gastroenterologie HK, s.r.o.

Hradec Králové, Czechia

Location

Artroscan

Ostrava, Czechia

Location

Research Site s.r.o.

Pilsen, Czechia

Location

Institute for Clinical and Experimental Medicine - IKEM

Prague, Czechia

Location

Clinique Pasteur

Toulouse, France

Location

Universitatsklinikum Heidelberg

Heidelberg, Germany

Location

Gastroenterologsiche Studiengesellschaft Herne

Hemer, Germany

Location

EUGASTRO GmbH

Leipzig, Germany

Location

Universitaetsklinikum Muenster

Münster, Germany

Location

Ospedale Policlinico San Martino - IRCCS

Genova, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, Italy

Location

IRCCS Istituto clinico humanitas - Humanitas Mirasole spa

Rozzano, Italy

Location

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

Krakow, Poland

Location

FutureMeds Warszawa Centrum

Warsaw, Poland

Location

Cluj County Clinical Emergency Hospital

Cluj-Napoca, Romania

Location

Gastromedica Srl

Iași, Romania

Location

Korea University Ansan Hospital

Ansan-si, South Korea

Location

Keimyung University Dongsan Hospital

Daegu, South Korea

Location

Kyungpook National University Hospital (KNUH)

Daegu, South Korea

Location

Pusan National University Hospital (PNUH)

Pusan, South Korea

Location

CHA Bundang Medical Center, CHA University

Seongnam-si, South Korea

Location

Seoul National University Bundang Hospital (SNUBH)

Seongnam-si, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

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

Seoul, South Korea

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro de Majadahonda

Majadahonda, Spain

Location

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

Sabadell, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

Aberdeen Royal Infirmary NHS Grampian Grampian Health Board

Aberdeen, United Kingdom

Location

Bradford Royal Infirmary - Bradford Teaching Hospitals NHS Foundation

Bradford, United Kingdom

Location

Frimley Park Hospital - Frimley Health NHS Foundation Trust

Frimley, United Kingdom

Location

Queen Elizabeth University Hospital - Greater Glasgow Health Board

Glasgow, United Kingdom

Location

Hull Royal Infirmary - Hull University Teaching Hospitals NHS Trust

Hull, United Kingdom

Location

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

London, United Kingdom

Location

King's College Hospital

London, United Kingdom

Location

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2024
• First Posted: April 25, 2024
• Study Start: July 9, 2024
• Primary Completion (Estimated): June 26, 2026
• Study Completion (Estimated): June 26, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and/or EU.
• Access Criteria: Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).

Locations

DE (4); ES (6); PL (2); US (20); RO (2); CZ (4); IT (4); GB (7); KR (10); FR (1)