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

A Double-blind, Randomized, Placebo-Controlled Study and Open-label Long Term Extension to Evaluate the Efficacy and Safety of Elafibranor 80 mg in Patients With Primary Biliary Cholangitis With Inadequate Response or Intolerance to Ursodeoxycholic Acid

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Biliary Cirrhosis
• Intervention / Treatment: Drug: Placebo; Drug: Elafibranor 80mg

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • CABA, Buenos Aires, Argentina, 1199
      • Hospital Italiano de Buenos Aires
    • CABA, Buenos Aires, Argentina, C1280AEB
      • Hospital Britanico de Buenos Aires
    • Caba, Buenos Aires, Argentina, C1118AAT
      • Hospital Aleman
    • La Plata, Buenos Aires, Argentina, 1900
      • Hospital Italiano de La Plata
  • Mendoza Province
    • Godoy Cruz, Mendoza Province, Argentina, 5547
      • Hospital Espanol de Mendoza
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2002KDS
      • Hospital Provincial del Centenario
• Belgium
  • Brussels, Belgium, 1070
    • Hôpital Erasme
  • Edegem, Belgium, 2650
    • Antwerp University Hospital
  • Ghent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • University Hospital Leuven
• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre
  • São Paulo
    • São Paulo, São Paulo, Brazil, 05403-000
      • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo-HCFMUSP
• Canada
  • Montreal, Canada, H2X 0A9
    • Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM)
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary Liver Unit - Heritage Medical Research Clinic (HMRC)
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z IM9
      • Gordon and Leslie Diamond Health Care Centre, Division of Gastroenterology
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
      • Shared Health Inc.-Operating as Health Sciences Centre-John Buhler Research Centre
• Chile
  • Santiago, Chile, 7550000
    • Clinica Universidad de Los Andes
  • Santiago, Chile, 8320000
    • Hospital Clínico Universidad de Chile
  • Santiago, Chile, 8330034
    • Centro de Investigacion Clinica Universidad Catolica CICUC
  • Coquimbo Region
    • La Serena, Coquimbo Region, Chile, 1700000
      • Hospital de La Serena
  • Valparaiso
    • Viña del Mar, Valparaiso, Chile, 2540364
      • Centro de Investigaciones Clinicas (CIC)
• France
  • Amiens, France, 80054
    • CHU Amiens Picardie
  • Créteil, France, 94000
    • Hôpital Henri Mondor
  • Grenoble, France, 38043
    • CHU Grenoble Alpes - Hôpital Albert Michallon
  • Orléans, France, 45067
    • Centre Hospitalier Régional D'orléans
  • Paris, France, 75012
    • Hôpital Saint-Antoine
  • Paris, France, 75014
    • Hopital Cochin
  • Paris, France, 75651
    • Hopital Pitie-Salpetriere
  • Pessac, France, 33604
    • Hopital Haut Leveque
  • Reims, France, 51092
    • Hôpital Robert Debré - CHU de Reims
  • Strasbourg, France, 67200
    • Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre
• Germany
  • Berlin, Germany, 10825
    • Gastro - Sudien
  • Berlin, Germany, 13353
    • Charite - Universitätsmedizin Berlin- CVK - Medizinische Klinik
  • Frankfurt, Germany, 60590
    • Universitätsklinikum Frankfurt
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Kiel, Germany, 24146
    • Center for Gastroenterology and Hepatology (GHZ) Kiel
  • Leipzig, Germany, 04103
    • Eugastro GmbH
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
  • Milan, Italy, 20142
    • Azienda Ospedaliera San Paolo, Dipartimento di Scienza della Salute, UO Medicina VI e Pathologia e Gastroenterologia
  • Monza, Italy, 20900
    • ASST Monza - Ospedale San Gerardo, Gastroenterologia
  • Padova, Italy, 35128
    • Azienda Ospedale- Università degli Studi di Padova UOC Gastroenterologia
  • Palermo, Italy, 90127
    • Azienda Ospedaliera Universitaria Policlinico P. Giaccone, UOC di Gastroenterologia-Dip.Medicina Interna e Specialistica
  • Località Baggiovara
    • Modena, Località Baggiovara, Italy, 41126
      • Ospedale Civile di Baggiovara-Struttura Complessa di Medicina ad indririzzo Metabolico Nutrizionale
• South Africa
  • Cape Town, South Africa, 7800
    • Mediclinic Constantiaberg, North Suites
  • Western Cap
    • Cape Town, Western Cap, South Africa, 7925
      • Groote Schuur Hospital, University of Cape Town - Clinical Research Centre
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7530
      • Tiervlei Trial Centre
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, C.P 28222
    • Hospital Universitario Puerta de Hierro -Madrid
  • Pontevedra, Spain, 36071
    • Complexo Hospitalario Universitario de Pontevedra
  • San Sebastián, Spain, 20014
    • Hospital Universitario Donostia
  • Santander, Spain, 39010
    • Hospital Universitario Marques de Valdecilla
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, Universitätsspital Bern Universitätsklinik für Viszerale chirurgie und Medizin Hepatologie
  • Lugano, Switzerland, 6900
    • Fondazione Epatocentro Ticino
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Hacette Universitesi Hastenesi IC, Hastaliklari Anabilim Dali, Gastronenteroloji Bilim Dali, Mithapasa Cad. Hacettepe Mah.
  • Bornova
    • Izmir, Bornova, Turkey (Türkiye), 35100
      • Ege Universitesi Tip Fakultesi Hastanesi
  • Pendik
    • Istanbul, Pendik, Turkey (Türkiye), 34890
      • Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Gastroentoloji Bilim Dali
• United Kingdom
  • Belfast, United Kingdom, BT12 6BA
    • Belfast Health and Social Care Trust-Royal Victoria Hospital
  • Camberley, United Kingdom, GU16 7UJ
    • Frimley Health NHS Foundation Trust - Frimley Park Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust - Addenbrookes Hospital
  • Hull, United Kingdom, HU32J
    • Hull University Teaching Hospitals NHS Trust , Hull Royal Infirmary
  • London, United Kingdom, SE5 9RS
    • King's College Hospital. King's College NHS Foundation Trust
  • Nottingham, United Kingdom, NG72UH
    • Nottingham University Hospitals NHS Trust - Queen's Medical Centre (QMC)
  • Plymouth, United Kingdom, PL6 8DH
    • Plymouth Hospitals NHS Trust, Derriford Hospital
  • Newcastle
    • Newcastle upon Tyne, Newcastle, United Kingdom, NE7 7DN
      • The Newcastle upon Tyne Hospitals NHS Foundation Trust-Freeman Hospital
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • The Institute for Liver Health
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group Inc.
    • Los Angeles, California, United States, 90033
      • Keck Medical Center of USC
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
    • San Francisco, California, United States, 94109
      • California Pacific Medical Center - Sutter Pacific Medical Foundation
  • Colorado
    • Aurora, Colorado, United States, 840045
      • University of Colorado Denver and Hospital
    • Englewood, Colorado, United States, 80113
      • South Denver Gastroenterology, P.C.
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine, Digestive Diseases
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Encore Borland-Groover Clinical Research
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Diseases/University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Digestive Healthcare of Georgia
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center (BIDMC)
  • Michigan
    • Novi, Michigan, United States, 48377
      • Henry Ford Health System
  • Missouri
    • St Louis, Missouri, United States, 63104
      • Saint Louis University
  • New York
    • New Hyde Park, New York, United States, 11042-11114
      • UPMC Center for Liver Diseases
    • New York, New York, United States, 10016
      • NYU Langone Health / NYU Grossman School of Medicine
    • New York, New York, United States, 10032
      • Columbia University Medical Center - Center for Liver Disease and Transplantation
    • New York, New York, United States, 10065
      • The New York-Presbyterian Hospital, David H. Koch Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Huntersville, North Carolina, United States, 28078
      • Carolinas Centre for Liver disease/ Atrium Health
  • Ohio
    • Cincinnati, Ohio, United States, 45249
      • Consultants for Clinical Research
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43210-1240
      • The Ohio State University Wexner Medical Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Investigational Drug Service Pharmacy Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina- College of Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Digestive Disease Center
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute, LLC
    • Dallas, Texas, United States, 75203
      • The Liver Institute at Methodist Dallas Medical Center
    • Dallas, Texas, United States, 75234
      • Liver Center of Texas, PLLC
    • Dallas, Texas, United States, 75390-8575
      • The University of Texas Southwestern Medical Center-IDS Aston Pharmacy
    • Fort Worth, Texas, United States, 76104
      • Texas Digestive Disease Consultants dba GI Alliance
    • Houston, Texas, United States, 77030
      • Liver Associates of Texas, P.A.
    • Houston, Texas, United States, 77030
      • St. Luke's Health-Baylor St Luke's Medical center - Advanced Liver Therapies Research
    • San Antonio, Texas, United States, 78215
      • American Research Corporation
    • Victoria, Texas, United States, 77904
      • Gastro health & Nutrition-Victoria
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center - Transplant Services
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital-Division of Gastroenterology, Hepatology, and Nutrition
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Medical Center
    • Newport News, Virginia, United States, 23602
      • Maryview Hospital Inc, Bon Secours Liver Institute of Hampton Roads
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Clinical Research Services Unit (CRSU)
    • Richmond, Virginia, United States, 23226
      • Richmond Community Hospital LLC, Bon Secours Liver Institute of Richmond
  • Washington
    • Seattle, Washington, United States, 98105
      • Liver Institute Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• 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

Exclusion Criteria:

• 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)
• Albumin<3.0 g/dl
• Severely advanced patients according to Rotterdam criteria (TB > ULN and albumin <LLN)
• INR > 1.3 due to altered hepatic function
• CPK > 2 x ULN
• Screening serum creatinine > 1.5 mg/dl
• Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as patients with markers of kidney failure damage or eGFR < 60 mL/min/1.73 m^2) calculated by Modification of diet in renal disease (MDRD)
• Platelet count < 150 x 10^3/μL
• AFP > 20 ng/mL with 4-phase liver CT or MRI imaging suggesting presence of liver cancer
• Known hypersensitivity to the investigational product or to any of the formulation excipients of the elafibranor or placebo tablet Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Elafibranor 80mg double-blind; Study participants will take 1 tablet per day orally before breakfast with a glass of water each morning	Drug: Elafibranor 80mg; Elafibranor 80mg daily; Other Names: Iqirvo®
Placebo Comparator: Placebo; Study participants will take 1 tablet per day orally before breakfast with a glass of water each morning	Drug: Placebo; Placebo daily
Experimental: Elafibranor 80mg open label; Study participants will take 1 tablet per day orally before breakfast with a glass of water each morning	Drug: Elafibranor 80mg; Elafibranor 80mg daily; Other Names: Iqirvo®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Key Secondary Endpoint: Percentage of Participants With Response to Treatment Based on ALP Normalization at Week 52	Response to treatment based on normalization of ALP at Week 52 was defined as percentage of participants with ALP =<1.0× ULN and based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to 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	The PBC Worst Itch NRS is a simple, self-administered patient reported outcome (PRO) questionnaire that measures itch intensity. Participants rate intensity of their worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Total score ranged from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicated worse outcomes. Baseline was defined as the average of the daily PBC Worst itch scores on available data within 14 days prior the day of randomization. Post-baseline data was defined as the average of the daily PBC Worst itch scores on available data in 4-week period intervals (available data every 28 days after the day of first study drug intake).	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	The PBC Worst Itch NRS is a simple, self-administered PRO questionnaire that measures itch intensity. Participants rate intensity of their worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Total score ranged from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicated worse outcomes. Baseline was defined as the average of the daily PBC Worst itch scores on available data within 14 days prior the day of randomization. Post-baseline data was defined as the average of the daily PBC Worst itch scores on available data in 4-week period intervals (available data every 28 days after the day of first study drug intake).	Baseline (up to 14 days pre-dose) and Week 24
Change From Baseline in ALP at Weeks 4, 13, 26, 39 and 52	Blood samples were collected at specified timepoints for assessment of ALP. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Weeks 4, 13, 26, 39 and 52
Percentage of Participants With ALP Response From Baseline at Week 52	ALP response was defined as ALP decrease from baseline >= 10%; ALP decrease from baseline >= 20% and ALP decrease from baseline >= 40% at Week 52 and based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Percentage of Participants With Response to Treatment According to ALP < 1.5x ULN, ALP Decrease From Baseline >= 40% and TB =<ULN at Week 52	Response to treatment was according to ALP < 1.5x ULN, ALP decrease from baseline >= 40% and TB =<ULN at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	At Week 52
Percentage of Participants With Response to Treatment According to ALP < 3x ULN, Aspartate Aminotransferase (AST) < 2x ULN and TB =< 1 Milligrams Per Deciliter (mg/dL) (Paris I) at Week 52	Response to treatment was according to ALP < 3x ULN, AST < 2x ULN and TB =< 1 mg/dL (Paris I) at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.	At Week 52
Percentage of Participants With Response to Treatment According to ALP =< 1.5x ULN, AST =< 1.5x ULN and TB =< 1 mg/dL (Paris II) at Week 52	Response to treatment was according to ALP =< 1.5x ULN, AST =< 1.5x ULN and TB =< 1 mg/dL (Paris II) at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.	At Week 52
Percentage of Participants With Response to Treatment According to TB Decrease of 15% Change From Baseline at Week 52	Response to treatment was according to TB decrease of 15% change from baseline at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	At Week 52
Percentage of Participants With Response to Treatment According to Normalization of TB (TB =< ULN) and/or Albumin (ALB >= Lower Limit of Normal [LLN]) (Rotterdam) at Week 52	Response to treatment was according to TB (TB =< ULN) and/or albumin (ALB >= LLN) (Rotterdam) at week 52. Participant was considered as responder at Week 52 only if total bilirubin and albumin were normal. The endpoint was analyzed in participants with abnormal total bilirubin (TB > ULN) or albumin (ALB < LLN) at baseline. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.	At Week 52
Percentage of Participants With Response to Treatment According to TB ≤0.6 x ULN at Week 52	Response to treatment was according to TB ≤0.6 x ULN at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.	At Week 52
Percentage of Participants With Response to Treatment According to ALP ≤1.67 x ULN and TB ≤1 mg/dL (Momah/ Lindor) at Week 52	Response to treatment was according to ALP ≤1.67 x ULN and TB ≤1 mg/dL (Momah/ Lindor) at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.	At Week 52
Percentage of Participants With Response to Treatment According to no Worsening of TB at Week 52	Response to treatment was according to no worsening of TB, which was defined as level of TB <ULN or no increase from baseline of more than 0.1 x ULN at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.	At Week 52
Percentage of Participants With Response to Treatment According to Complete Biochemical Response at Week 52	Response to treatment according to complete biochemical response which was defined as <= ULN values of ALP, TB, AST, ALT and ALB, and international normalized ratio (INR) at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.	At Week 52
PBC 5-, 10- and 15-year Risk Scores Based on United Kingdom (UK)-PBC Score at Week 52	The UK-PBC risk score was defined by the mean percentage risk that a PBC participant treated with UDCA would develop liver failure requiring liver transplantation in 5, 10, and 15 years from diagnosis. It is calculated from the following equation at week 52 as follows: UK-PBC score = 0.0287854*(alpEPxULN-1.722136304) - 0.0422873*([{altastEP x ULN/10}^-1] - 8.675729006) + 1.4199 * (LN(bilEPxULN /10)+2.709607778) - 1.960303*(alb x LLN -1.17673001)-0.4161954*(plt x LLN -1.873564875). The survival S(t) for any given participants was then calculated by S(t) = S0(t) exp(UK-PBC score). Here, alpEP x ULN=ALP /Upper Level Normal ALP at the timepoint, altastEPxULN=(ALT, AST or TA) /upper level normal of the value at the timepoint, bilEP x ULN=bilirubin /upper level normal bilirubin at the timepoint, alb x LLN=alb /alb lower level normal at baseline and plt x LLN=plt/plt lower level normal at baseline. Lower UK-PBC score predicts lower risk and better prognosis.	At Week 52
Global PBC Study Group (GLOBE) Score at Week 52	The GLOBE score was a validated risk assessment tool providing an estimate of transplant-free survival for participants with PBC. It was developed by the Global PBC Study Group using Cox regression model on over 4,000 participants with PBC. It is calculated from the following equation at week 52 as follows: GLOBE score = 0.044378 * age at start of ursodeoxycholic acid (UDCA) therapy + 0.93982 * LN (TB x ULN) + 0.335648 * LN (ALP x ULN) - 2.266708 * ALB x LLN - 0.002581 * platelet count per 10^9/L) + 1.216865; where TB x ULN = bilirubin/ULN at the timepoint, ALP x ULN = ALP/ULN at the timepoint, ALB x LLN = ALB/LLN at the timepoint, platelet count per 10^9/L = platelet count per 10^9/L at the timepoint. The Lower GLOBE PBC score predicts lower risk and better prognosis.	At Week 52
Change From Baseline in Hepatobiliary Injury and Liver Function as Assessed by AST, ALT, Gamma-glutamyl Transferase (GGT), 5 Prime Nucleotidase (5'-NT), and Fractionated ALP (Hepatic) (H1 and H2) at Week 52	Hepatobiliary injury and liver function were assessed as measured by AST, ALT, GGT, 5'-NT, and fractionated ALP (hepatic) (H1 and H2). Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Hepatobiliary Injury and Liver Function as Measured by Total and Conjugated Bilirubin at Week 52	Hepatobiliary injury and liver function were assessed as measured by total and conjugated bilirubin. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Hepatobiliary Injury and Liver Function as Measured by Albumin at Week 52	Hepatobiliary injury and liver function were assessed as measured by albumin. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Hepatobiliary Injury and Liver Function as Measured by INR at Week 52	Hepatobiliary injury and liver function were assessed as measured by INR. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Biomarkers of Inflammation as Measured by High-sensitivity C-reactive Protein (hsCRP) at Week 52	Biomarkers of inflammation were assessed as measured by hsCRP. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Biomarkers of Inflammation as Measured by Fibrinogen and Haptoglobin at Week 52	Biomarkers of inflammation were assessed as measured by fibrinogen and haptoglobin. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Biomarkers of Inflammation as Measured by Tumor Necrosis Factor Alpha at Week 52	Biomarkers of inflammation were assessed as measured by TNF-alpha. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Immune Response as Measured by Immunoglobulin (Ig)G and IgM at Week 52	Immune response was assessed as measured by IgG and IgM. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Enhanced Liver Fibrosis (ELF) and Plasminogen Activator Inhibitor-1 (PAI-1) at Week 52	Biomarkers and non-invasive measures of hepatic fibrosis were assessed as measured by ELF: hyaluronic acid [HA], type 2 procollagen peptide [PIINP], tissue inhibitor of metalloproteinases-1[TIMP-1]) and PAI-1. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Cytokeratin-18 (CK-18) at Week 52	Biomarkers and non-invasive measures of hepatic fibrosis were assessed as measured by CK-18 (M30 and M65). Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Transforming Growth Factor Beta (TGF-beta) at Week 52	Biomarkers and non-invasive measures of hepatic fibrosis were assessed as measured by TGF-beta. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Liver Stiffness Measured by Transient Elastography (TE) at Week 52	FibroScan® TE device (Echosens, Paris, France) is a non-invasive technique used to measure liver stiffness, which correlated with fibrosis. Baseline was defined as the last non-missing value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Lipid Parameters at Week 52	Blood samples were collected at specified timepoints for assessment of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol and triglycerides (TG). Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52	Blood samples were collected at specified timepoints for assessment of FPG. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52	Blood samples were collected at specified timepoints for assessment bile acids and biomarkers of bile acid synthesis. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline at Week 52 in Bile Acids and Biomarkers of Bile Acid Synthesis as Measured by 7 Alpha-hydroxy-4-cholesten-3-one (C4) at Week 52	Blood samples were collected at specified timepoints for assessment of bile acids and biomarkers of bile acid synthesis as measured by C4. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis as Measured Fibroblast Growth Factor 19 at Week 52	Blood samples were collected at specified timepoints for assessment bile acids and biomarkers of bile acid synthesis as measured by Fibroblast Growth Factor 19. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Percentage of Participants With Response in PBC Worst Itch NRS Score at Weeks 24 and 52	The PBC Worst Itch NRS is a simple, self-administered PRO questionnaire that measures itch intensity. Participants rate intensity of their worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Total score ranged from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicated worse outcomes. Response to PBC Worst Itch NRS was according to clinically meaningful change at least 30% reduction; one point, two points or three points decrease in score from baseline in participants with a baseline NRS score ≥4. Baseline was defined as the average of the daily PBC Worst itch scores on available data within 14 days prior the day of randomization. Post-baseline data was defined as the average of the daily PBC Worst itch scores on available data in 4-week period intervals (available data every 28 days after the day of first study drug intake).	Baseline (up to 14 days pre-dose) and at Week 24 and Week 52
Percentage of Participants With no Worsening of Pruritus as Measured by the PBC Worst Itch NRS Score at Weeks 24 and 52	The PBC Worst Itch NRS is a simple, self-administered PRO questionnaire that measures itch intensity. Participants rate intensity of their worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Total score ranged from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicated worse outcomes. Baseline was defined as the average of the daily PBC Worst itch scores on available data within 14 days prior the day of randomization. Post-baseline data was defined as the average of the daily PBC Worst itch scores on available data in 4-week period intervals (available data every 28 days after the day of first study drug intake). A worsening of Pruritus was defined by a positive change from baseline in PBC Worst Itch NRS score greater than 2 at week 24 and 52.	Baseline (up to 14 days pre-dose) and at Week 24 and Week 54
Change From Baseline in 5-D Itch at Week 52	The 5-D Itch scale is a questionnaire that has been validated in several different diseases. It assesses symptoms in terms of 5 domains: duration: score range 1 (less than 6 hours) to 5 (all day); degree: score range 1 (not present) to 5 (unbearable); duration: score range 1 (less than 6 hours) and 5 (all day); direction: score range 1(completely resolved) and 5 (getting worse); disability: score range 1 (never affects or not applicable) and 5 (delays falling asleep and frequently wakes up at night or always affects this activity) and distribution: where the question was to mark where itching is present in body parts over the last two weeks. Participants rated their symptoms over preceding 2-week period on a 1 to 5 scale, with 5 being the most affected. The 5-D Itch total score ranged between 5 (no pruritus) and 25 (most severe pruritus). Higher scores indicated worse outcomes. Baseline= last non-missing value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a at Week 52	The PROMIS Fatigue Short Form 7a consists of seven items that measure both the experience of fatigue and the interference of fatigue on daily activities over the past week. Participants completed the PROMIS Fatigue Short Form 7a and answered following questions on a scale from 1 (never) to 5 (always) : "How often did you feel tired"; "How often did you experience extreme exhaustion"; "How often did you run out of energy"; "How often did your fatigue limit you at work"; "How often were you too tired to think clearly"; "How often were you too tired to take a bath or shower" and 'How often did you have enough energy to exercise strenuously". T-score values include mean of 50 and standard deviation of 10. The PROMIS Fatigue T-score ranged from 29.4 (best) to 83.2 (worst). Higher scores indicated worse outcomes. Baseline was defined as the last non-missing value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Epworth Sleepiness Scale (ESS) at Week 52	The ESS is a short, self-administered questionnaire that consists of 8 questions asking to rate how likely it is to fall asleep in everyday situations (each question can be scored from 0 to 3 points; '0' indicates no chance of dozing and '3' indicates high chance of dozing). It provides a total score which has been shown to relate to the participant's level of daytime sleepiness (total score range 0 [no sleepiness] to 24 points [significant sleepiness]). The total score is the sum of all item scores and ranged from 0 (best) to 24 (worst). Higher scores indicated more chances of sleepiness. Participants were asked to complete the ESS with regard to the level of sleepiness they experienced over approximately the past 7 days. Baseline was defined as the last non-missing value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in PBC-40 at Week 52	PBC-40 assess symptoms across 6 domains:symptoms,itch,fatigue,cognitive,emotional and social. Participants responded on verbal response scale,depending on section options range from 'never'/'not at all'/'strongly disagree' to 'always'/'very much'/'strongly agree'.5 items (3/3 in itch domain and 2/10 in social domain)also included a 'does not apply' option.Domains:Symptoms(7 questions)score range 7-35,Itch(3 questions)score range 3-15,Fatigue(11 questions)score range 11-55,Cognitive(6 questions)score range 6-30,Emotional(3 questions)score range 3-15,Social(10 questions)score range 10-50.Score for each domain was provided(total score was not calculated),with each verbal response scale correlating to score of 1-5 per item(0-5 on items with a 'does not apply' option);5=most affected.Individual item scores are summed to give total domain score.Higher scores=worse outcomes.PBC-40 had 4-week recall period.Baseline=last non-missing value on or before first dose of randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Health Utility as Measured by the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) at Week 52	The EQ-5D-5L is a 6-item, standardized questionnaire that assesses mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and overall health state. The visual analog scale (VAS) of EQ-5D-5L questionnaire is numbered from 0 (worst) to 100 (best). Higher scores indicated better outcomes. Baseline was defined as the last non-missing value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in T-Scores for Bone Mineral Density Assessed by Dual-energy X-ray Absorptiometry (DEXA) Scanning at Week 52	DEXA scanning (hip and lumbar) was performed in participants to assess bone mineral density (femoral neck, lumbar and total hip). T-scores were calculated based on actual measured bone density value. The T-score compared a participant's bone density against that of a healthy 30-year-old adult. T-scores were used to determine primary osteoporosis, which exists on its own without any other cause and were divided into 3 categories: low risk, medium risk, and high risk (osteoporosis). T-scores measure the number of minerals in a participant's bone. A participant's level of bone loss was compared to that of a typical, healthy 30-year-old adult. A score ≥-1.0 indicates low risk, medium risk is a score between-2.5 and -1.0, and a high risk/osteoporosis is a score ≤-2.5. A positive change in T-score indicates an improvement in bone mineral density. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Serum Markers of Bone Turnover Carboxy Terminal Crosslinked Telopeptides of Type 1 Collagen [CTX] at Week 52	Blood samples were collected at specified timepoints for assessment of serum markers of bone turnover, CTX. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Change From Baseline in Serum Markers of Bone Turnover Type 1 Procollagen Peptide [P1NP]) at Week 52	Blood samples were collected at specified timepoints for assessment of serum markers of bone turnover, P1NP. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.	Baseline (Day 1) and at Week 52
Percentage of Participants With Onset of Clinical Outcomes	Onset of clinical outcomes were described as a composite endpoint composed of the following: model for end stage liver disease sodium (MELD-Na) >14 for participants with baseline MELD-Na <12; liver transplant; uncontrolled ascites requiring treatment; hospitalization for new onset or recurrence of any including, variceal bleed, hepatic encephalopathy defined as West-Haven score of 2 or more and spontaneous bacterial peritonitis; and death.	From Day 1 up to Week 52
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs)	An AE was any untoward medical occurrence in a participant or clinical investigation participant who was administered an investigational product, and which does not necessarily have a causal relationship with treatment. A TEAE was defined as any AE with onset during TEAE assessment period, or any event started prior to first dose of treatment and worsened or became serious during the TEAE assessment period. An SAE was any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality/birth defect. An AESI was an AE that might not be serious but was of special importance to a particular treatment or class.	TEAEs were collected from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days.
Plasma Concentrations of Elafibranor and GFT1007	Blood samples were collected at specified timepoints to evaluate plasma concentration of Elafibranor and its metabolite GFT1007.	Week 4: pre-dose, 0.5 hour, 1.5 hours, between 2-3 hours, 4 hours and 6 hours post-dose

Collaborators and Investigators

• Sponsor: Ipsen
• Investigators: Study Director: Ipsen Medical Director, Ipsen

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2020
• Primary Completion (Actual): June 1, 2023
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: August 21, 2020
• First Submitted That Met QC Criteria: August 21, 2020
• First Posted (Actual): August 26, 2020

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Primary Biliary Cholangitis; Elafibranor; PBC
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Bile Duct Diseases; Fibrosis; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Pathological Conditions, Signs and Symptoms; Liver Cirrhosis, Biliary; Substandard Drugs; Pharmaceutical Preparations; 2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid
• Other Study ID Numbers: GFT505B-319-1; 2019-004941-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications.

Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.

• IPD Sharing 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.
• IPD Sharing 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/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No