Study of Elafibranor in Patients With Primary Biliary Cholangitis (PBC)

NCT04526665 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: GFT505B-319-12019-004941-34
• Study Type: interventional
• Target: 161
• Locations: 14 countries
• Sites: 115

Brief Summary

The participants of this study will have confirmed Primary Biliary Cholangitis (PBC) with inadequate response or intolerance to ursodeoxycholic acid (which is a medication used in the management and treatment of cholestatic liver disease). PBC is a slowly progressive disease characterized by damage of the bile ducts in the liver, leading to a buildup 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 liver transplant or may die if the disease progresses and a liver transplant is not done. The main aim of this study is to determine if elafibranor (the study drug) is better than placebo (a dummy treatment) at decreasing the levels of a specific blood test (alkaline phosphatase) that provides information about participant's disease. This study will also evaluate the safety of long-term treatment with elafibranor, as well as the impact on symptoms such as itchy skin (pruritus) and tiredness (fatigue). This study has two main parts: Part 1 will compare a daily dose of elafibranor to a daily dose of placebo and will last between a minimum of one year and a maximum of two years. Part 2, all participants will receive elafibranor for a period of up to 5 years or until the total treatment duration (part 1 and part 2) reaches 6 years, whichever occurs first.

Conditions

Primary Biliary Cirrhosis

Keywords

Primary Biliary Cholangitis; PBC; Elafibranor

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Response to Treatment Based on Cholestasis Response at Week 52

  Cholestasis response was defined as alkaline phosphatase (ALP) \< 1.67 x upper limit of normal (ULN) and total bilirubin (TB) \<= ULN and ALP decrease from baseline \>= 15% at Week 52 and based on the composite strategy imputing non-response for participants who experienced intercurrent events (ICEs) (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.

  At Week 52

Secondary Outcomes (46)

• Key Secondary Endpoint: Percentage of Participants With Response to Treatment Based on ALP Normalization at Week 52

  At Week 52

• Key Secondary Endpoint: Change From Baseline in Pruritus Based on PBC Worst Itch Numeric Rating Scale (NRS) Score in Participants With Baseline PBC Worst Itch NRS Score ≥4 to Week 52

  Baseline (up to 14 days pre-dose) and Week 52

• Key Secondary Endpoint: Change From Baseline in Pruritus Based on PBC Worst Itch NRS Score in Participants With Baseline PBC Worst Itch NRS Score ≥4 to Week 24

  Baseline (up to 14 days pre-dose) and Week 24

• Change From Baseline in ALP at Weeks 4, 13, 26, 39 and 52

  Baseline (Day 1) and at Weeks 4, 13, 26, 39 and 52

• Percentage of Participants With ALP Response From Baseline at Week 52

  Baseline (Day 1) and at Week 52

Study Arms (3)

Elafibranor 80mg double-blind

EXPERIMENTAL

Study participants will take 1 tablet per day orally before breakfast with a glass of water each morning

Drug: Elafibranor 80mg

Placebo

PLACEBO COMPARATOR

Study participants will take 1 tablet per day orally before breakfast with a glass of water each morning

Drug: Placebo

Elafibranor 80mg open label

EXPERIMENTAL

Study participants will take 1 tablet per day orally before breakfast with a glass of water each morning

Drug: Elafibranor 80mg

Interventions

Elafibranor 80mg DRUG

Elafibranor 80mg daily

Also known as: Iqirvo®

Elafibranor 80mg double-blind; Elafibranor 80mg open label

Placebo DRUG

Placebo daily

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females age of 18 to 75 years (inclusive)
• Definite or probable Primary biliary cholangitis (PBC) diagnosis
• Alkaline phosphatase (ALP) ≥ 1.67x upper limit of normal (ULN)
• Total bilirubin (TB) ≤ 2x ULN
• Ursodeoxycholic acid (UDCA) for at least 12 months (stable dose ≥ 3 months) prior to screening, or unable to tolerate UDCA treatment (no UDCA for ≥ 3 months) prior to screening (per country standard-of-care dosing)
• Must have PBC Worst Itch Numeric rating scale (NRS) collected prior to randomization
• Females participating in this study must be of non-child bearing potential or must be using highly efficient contraception for the full duration of the study and for 1 month after the last drug intake

You may not qualify if:

• History or presence of other concomitant liver disease
• Clinically significant hepatic decompensation, including patients with complications of cirrhosis/portal hypertension
• Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease) or which may diminish life expectancy to \< 2 years, including known cancers
• Patient has a positive test for HIV Type 1 or 2 at screening, or patient is known to have tested positive for HIV
• Evidence of any other unstable or untreated clinically significant disease
• History of alcohol abuse
• For female patients: known pregnancy or lactating
• Use of fibrates and glitazones within 2 months prior to screening
• Use of Obeticholic acid (OCA), azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids (parenteral and oral chronic administration only); potentially hepatotoxic drugs
• (including α-methyl-dopa, sodium valproic acid isoniazid, or nitrofurantoin) within 3 months prior to screening
• Use of antibodies or immunotherapy directed against interleukins (ILs) or other cytokines or chemokines within 12 months prior to screening
• For patients with previous exposure to OCA, OCA should be discontinued 3 months prior to screening
• Patients 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 five half-lives, whichever is longer, prior to screening; for patients with previous exposure to seladelpar, seladelpar should be discontinued 3 months prior to screening
• Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) values \> 5 x ULN
• For patients with AT or TB\>ULN at SV1, variability of AT or TB \> 40% (see section 3.5.1)

Sponsors & Collaborators

• Ipsen: lead

Study Sites (115)

The Institute for Liver Health

Chandler, Arizona, 85224, United States

Location

Keck Medical Center of USC

Los Angeles, California, 90033, United States

Location

Ruane Clinical Research Group Inc.

Los Angeles, California, 90036, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

California Pacific Medical Center - Sutter Pacific Medical Foundation

San Francisco, California, 94109, United States

Location

University of Colorado Denver and Hospital

Aurora, Colorado, 840045, United States

Location

South Denver Gastroenterology, P.C.

Englewood, Colorado, 80113, United States

Location

Yale School of Medicine, Digestive Diseases

New Haven, Connecticut, 06510, United States

Location

Encore Borland-Groover Clinical Research

Jacksonville, Florida, 32256, United States

Location

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, 33136, United States

Location

Digestive Healthcare of Georgia

Atlanta, Georgia, 30309, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health System

Novi, Michigan, 48377, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

UPMC Center for Liver Diseases

New Hyde Park, New York, 11042-11114, United States

Location

NYU Langone Health / NYU Grossman School of Medicine

New York, New York, 10016, United States

Location

Columbia University Medical Center - Center for Liver Disease and Transplantation

New York, New York, 10032, United States

Location

The New York-Presbyterian Hospital, David H. Koch Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Carolinas Centre for Liver disease/ Atrium Health

Huntersville, North Carolina, 28078, United States

Location

Consultants for Clinical Research

Cincinnati, Ohio, 45249, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210-1240, United States

Location

Investigational Drug Service Pharmacy Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina- College of Medicine

Charleston, South Carolina, 29425, United States

Location

Vanderbilt Digestive Disease Center

Nashville, Tennessee, 37232, United States

Location

Texas Clinical Research Institute, LLC

Arlington, Texas, 76012, United States

Location

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

Liver Center of Texas, PLLC

Dallas, Texas, 75234, United States

Location

The University of Texas Southwestern Medical Center-IDS Aston Pharmacy

Dallas, Texas, 75390-8575, United States

Location

Texas Digestive Disease Consultants dba GI Alliance

Fort Worth, Texas, 76104, United States

Location

Liver Associates of Texas, P.A.

Houston, Texas, 77030, United States

Location

St. Luke's Health-Baylor St Luke's Medical center - Advanced Liver Therapies Research

Houston, Texas, 77030, United States

Location

American Research Corporation

San Antonio, Texas, 78215, United States

Location

Gastro health & Nutrition-Victoria

Victoria, Texas, 77904, United States

Location

Intermountain Medical Center - Transplant Services

Murray, Utah, 84107, United States

Location

University of Utah Hospital-Division of Gastroenterology, Hepatology, and Nutrition

Salt Lake City, Utah, 84132, United States

Location

University of Virginia Medical Center

Charlottesville, Virginia, 22908, United States

Location

Maryview Hospital Inc, Bon Secours Liver Institute of Hampton Roads

Newport News, Virginia, 23602, United States

Location

Richmond Community Hospital LLC, Bon Secours Liver Institute of Richmond

Richmond, Virginia, 23226, United States

Location

Virginia Commonwealth University Clinical Research Services Unit (CRSU)

Richmond, Virginia, 23298, United States

Location

Liver Institute Northwest

Seattle, Washington, 98105, United States

Location

Hospital Italiano de Buenos Aires

CABA, Buenos Aires, 1199, Argentina

Location

Hospital Alemán

Caba, Buenos Aires, C1118AAT, Argentina

Location

Hospital Británico de Buenos Aires

CABA, Buenos Aires, C1280AEB, Argentina

Location

Hospital Italiano de La Plata

La Plata, Buenos Aires, 1900, Argentina

Location

Hospital Espanol De Mendoza

Godoy Cruz, Mendoza Province, 5547, Argentina

Location

Hospital Provincial del Centenario

Rosario, Santa Fe Province, S2002KDS, Argentina

Location

Hôpital Erasme

Brussels, 1070, Belgium

Location

Antwerp University Hospital

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

University Hospital Leuven

Leuven, 3000, Belgium

Location

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo-HCFMUSP

São Paulo, São Paulo, 05403-000, Brazil

Location

University of Calgary Liver Unit - Heritage Medical Research Clinic (HMRC)

Calgary, Alberta, T2N 4Z6, Canada

Location

Gordon and Leslie Diamond Health Care Centre, Division of Gastroenterology

Vancouver, British Columbia, V5Z IM9, Canada

Location

Shared Health Inc.-Operating as Health Sciences Centre-John Buhler Research Centre

Winnipeg, Manitoba, R3E 3P4, Canada

Location

Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM)

Montreal, H2X 0A9, Canada

Location

Hospital de La Serena

La Serena, Coquimbo Region, 1700000, Chile

Location

Centro de Investigaciones Clinicas (CIC)

Viña del Mar, Valparaiso, 2540364, Chile

Location

Clínica Universidad de los Andes

Santiago, 7550000, Chile

Location

Hospital Clínico Universidad de Chile

Santiago, 8320000, Chile

Location

Centro de Investigacion Clinica Universidad Catolica CICUC

Santiago, 8330034, Chile

Location

CHU Amiens Picardie

Amiens, 80054, France

Location

Hôpital Henri Mondor

Créteil, 94000, France

Location

CHU Grenoble Alpes - Hôpital Albert Michallon

Grenoble, 38043, France

Location

Centre Hospitalier Régional d'Orléans

Orléans, 45067, France

Location

Hôpital Saint-Antoine

Paris, 75012, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Hôpital Pitié-Salpétrière

Paris, 75651, France

Location

Hôpital Haut Lévêque

Pessac, 33604, France

Location

Hôpital Robert Debré - CHU de Reims

Reims, 51092, France

Location

Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre

Strasbourg, 67200, France

Location

Gastro - Sudien

Berlin, 10825, Germany

Location

Charite - Universitätsmedizin Berlin- CVK - Medizinische Klinik

Berlin, 13353, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Center for Gastroenterology and Hepatology (GHZ) Kiel

Kiel, 24146, Germany

Location

EUGASTRO GmbH

Leipzig, 04103, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Ospedale Civile di Baggiovara-Struttura Complessa di Medicina ad indririzzo Metabolico Nutrizionale

Modena, Località Baggiovara, 41126, Italy

Location

Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi

Bologna, 40138, Italy

Location

Azienda Ospedaliera San Paolo, Dipartimento di Scienza della Salute, UO Medicina VI e Pathologia e Gastroenterologia

Milan, 20142, Italy

Location

ASST Monza - Ospedale San Gerardo, Gastroenterologia

Monza, 20900, Italy

Location

Azienda Ospedale- Università degli Studi di Padova UOC Gastroenterologia

Padova, 35128, Italy

Location

Azienda Ospedaliera Universitaria Policlinico P. Giaccone, UOC di Gastroenterologia-Dip.Medicina Interna e Specialistica

Palermo, 90127, Italy

Location

Tiervlei Trial Centre

Cape Town, Western Cape, 7530, South Africa

Location

Groote Schuur Hospital, University of Cape Town - Clinical Research Centre

Cape Town, Western Cap, 7925, South Africa

Location

Mediclinic Constantiaberg, North Suites

Cape Town, 7800, South Africa

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Puerta de Hierro -Madrid

Madrid, C.P 28222, Spain

Location

Complexo Hospitalario Universitario de Pontevedra

Pontevedra, 36071, Spain

Location

Hospital Universitario Donostia

San Sebastián, 20014, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39010, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Inselspital, Universitätsspital Bern Universitätsklinik für Viszerale chirurgie und Medizin Hepatologie

Bern, 3010, Switzerland

Location

Fondazione Epatocentro Ticino

Lugano, 6900, Switzerland

Location

Ege Universitesi Tip Fakultesi Hastanesi

Izmir, Bornova, 35100, Turkey (Türkiye)

Location

Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Gastroentoloji Bilim Dali

Istanbul, Pendik, 34890, Turkey (Türkiye)

Location

Hacette Universitesi Hastenesi IC, Hastaliklari Anabilim Dali, Gastronenteroloji Bilim Dali, Mithapasa Cad. Hacettepe Mah.

Ankara, 06230, Turkey (Türkiye)

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust-Freeman Hospital

Newcastle upon Tyne, Newcastle, NE7 7DN, United Kingdom

Location

Belfast Health and Social Care Trust-Royal Victoria Hospital

Belfast, BT12 6BA, United Kingdom

Location

Frimley Health NHS Foundation Trust - Frimley Park Hospital

Camberley, GU16 7UJ, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust - Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Hull University Teaching Hospitals NHS Trust , Hull Royal Infirmary

Hull, HU32J, United Kingdom

Location

King's College Hospital. King's College NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Nottingham University Hospitals NHS Trust - Queen's Medical Centre (QMC)

Nottingham, NG72UH, United Kingdom

Location

Plymouth Hospitals NHS Trust, Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Related Publications (2)

• Levy C, Bowlus CL, Lawitz E, Antunes N, Miller B, Shu J, Zein CO, Kowdley KV. Baseline Alkaline Phosphatase Impacts Response Rates in Primary Biliary Cholangitis: Exploring Response to Elafibranor in ELATIVE. Liver Int. 2026 May;46(5):e70630. doi: 10.1111/liv.70630.

  PMID: 41937506 DERIVED

• Kowdley KV, Bowlus CL, Levy C, Akarca US, Alvares-da-Silva MR, Andreone P, Arrese M, Corpechot C, Francque SM, Heneghan MA, Invernizzi P, Jones D, Kruger FC, Lawitz E, Mayo MJ, Shiffman ML, Swain MG, Valera JM, Vargas V, Vierling JM, Villamil A, Addy C, Dietrich J, Germain JM, Mazain S, Rafailovic D, Tadde B, Miller B, Shu J, Zein CO, Schattenberg JM; ELATIVE Study Investigators' Group; ELATIVE Study Investigators' Group. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. N Engl J Med. 2024 Feb 29;390(9):795-805. doi: 10.1056/NEJMoa2306185. Epub 2023 Nov 13.

  PMID: 37962077 DERIVED

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

Results Point of Contact

• Title: Medical Director
• Organization: Ipsen

clinical.trials@ipsen.com

see email

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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

Model Details: This is a double-blind (DB), randomized, placebo-controlled study followed by an open-label long term extension (LTE)

Study Record Dates

• First Submitted: August 21, 2020
• First Posted: August 26, 2020
• Study Start: September 24, 2020
• Primary Completion: June 1, 2023
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 1, 2026
• Results First Posted: September 5, 2024

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

CA (4); GB (8); BE (4); DE (7); ZA (3); AR (6); CL (5); BR (2); FR (10); CH (2); TU (3); IT (6); ES (9); US (46)