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.

This study has two main parts; the first part will compare a daily dose of elafibranor (the study drug) to a daily dose of placebo (a dummy treatment), and will last between a minimum of one year and a maximum of two years. In the second part, all participants will receive elafibranor, for a period between 4-5 years.

The main aim of this study is to determine if elafibranor is better than placebo at decreasing the levels of a specific blood test (alkaline phosphatase) that provides information about participant's disease. This study will also study the safety of long-term treatment with elafibranor, as well as the impact on symptoms such as pruritus and fatigue.

Study Overview

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

• 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, C1118AAT
      • Hospital Aleman
    • Caba, Buenos Aires, Argentina, C1280AEB
      • Hospital Británico de Buenos Aires
  • Mendoza
    • Godoy Cruz, Mendoza, Argentina, 5547
      • Hospital Espanol de Mendoza
  • Provincia De Buenos Aires
    • La Plata, Provincia De Buenos Aires, Argentina, 1900
      • Hospital Italiano de la Plata
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2002KDS
      • Hospital Provincial del Centenario
• Belgium
  • Brussels, Belgium, 1070
    • Hôpital Erasme
  • Edegem, Belgium, 2650
    • Antwerp University Hospital
  • Gent, 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
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 05403-000
      • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo-HCFMUSP
• Canada
  • Montréal, Canada, H2X 0A9
    • Centre de Recherche du Centre Hospitalier de l'Universite 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 Clinico Universidad de Chile
  • Santiago, Chile, 8330034
    • Centro de Investigacion Clinica Universidad Catolica CICUC
  • Coquimbo
    • La Serena, Coquimbo, Chile, 1700000
      • Hospital de La Serena
  • Region De Valparaiso
    • Viña Del Mar, Region De 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 Regional D'Orleans
  • Paris, France, 75012
    • Hôpital Saint-Antoine
  • Paris, France, 75014
    • Hôpital Cochin
  • Paris, France, 75651
    • Hôpital Pitié-Salpêtrière
  • 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
    • Universitatsklinikum Frankfurt
  • Hannover, 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
  • Milano, 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 Marqués de Valdecilla
  • Sevilla, 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
  • Ankara, Turkey, 06230
    • Hacette Universitesi Hastenesi IC, Hastaliklari Anabilim Dali, Gastronenteroloji Bilim Dali, Mithapasa Cad. Hacettepe Mah.
  • Bornova
    • İzmir, Bornova, Turkey, 35100
      • Ege Universitesi Tip Fakultesi Hastanesi
  • Pendik
    • Istanbul, Pendik, Turkey, 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
    • Saint 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 PBC diagnosis
• ALP ≥ 1.67x upper limit of normal (ULN)
• Total bilirubin (TB) ≤ 2x ULN
• 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 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 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 obeticholic acid (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
• ALT and/or 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 m2) calculated by MDRD
• Platelet count < 150 x 103/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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Elafibranor 80mg; Study subjects will take 1 tablet per day orally before breakfast with a glass of water each morning	Drug: Elafibranor 80mg; Elafibranor 80mg daily
Placebo Comparator: Placebo; Study subjects will take 1 tablet per day orally before breakfast with a glass of water each morning	Drug: Placebo; Placebo daily for double blind period and elafibranor 80 mg daily fo the open label period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants with response to treatment measured by the combination levels of Alkaline Phosphate Levels (ALP) and Total Bilirubin (TB)	At Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants who normalised ALP levels		At Week 52
Change in pruritus from baseline in participants with baseline PBC Worst Itch NRS Score ≥ 4		Through 52 weeks of treatment
Change in pruritus from baseline in participants with baseline PBC Worst Itch NRS Score ≥ 4		Through 24 weeks of treatment
Change from baseline in ALP levels		At Week 4, 13, 26, 39 and Week 52 and up to a maximum of 6 years
Percentage of participants with ≥10%, ≥20%, and ≥40% decrease from Baseline in ALP Levels		From baseline to Week 52 and up to a maximum of 6 years
Percentage of Participants with response to treatment	Based on different biochemical response criteria	At Week 52 and up to a maximum of 6 years
Change from baseline in PBC risk scores based on United Kingdom (UK)-PBC score.	the UK-PBC risk score estimates the risk that a patient with PBC will require liver transplantation within 5, 10 or 15 years. A high number is indicative of a worse prognosis.	At Week 52 and up to a maximum of 6 years
Change from baseline in Global PBC Study Group (GLOBE) score	The GLOBE score is a prognostic tool used to identify patients with PBC who are at higher/lower risk of liver transplant or death. A high number is indicative of a worse prognosis.	At Week 52 and up to a maximum of 6 years
Percentage of participants who normalised bilirubin levels		At Week 52 and up to a maximum of 6 years
Percentage of participants who normalised albumin levels		At Week 52 and up to a maximum of 6 years
Change from baseline in levels of aspartate aminotransferase (AST)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of alanine aminotransferase (ALT )		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of gamma-glutamyl transferase (GGT)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of 5'-nucleotidase (5' NT)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of total and conjugated bilirubin		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of albumin		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in international normalised ratio (INR)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in fractionated alkaline phosphatase (ALP)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of high sensitivity C-reactive protein (hsCRP)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of fibrinogen		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of haptoglobin		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of tumor necrosis factor-alpha (TNF-α)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of immunoglobulin G (IgG)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of immunoglobulin M (IgM)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in enhanced liver fibrosis (ELF) score		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of plasminogen activator inhibitor-1 (PAI-1)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of transforming growth factor beta (TGF-β)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of cytokeratin-18 (CK-18) (M65 and M30)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of Pro-C3		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in liver stiffness as measured by Transient Elastography (TE)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of total cholesterol (TC)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of low density lipoprotein cholesterol (LDL-C)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of high density lipoprotein cholesterol (HDL-C)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in calculated very low density lipoprotein cholesterol (VLDL-C)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of triglycerides (TG)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in Fasting Plasma Glucose (FPG)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of individual bile acids		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of 7-α-hydroxy-4-cholesten-3-one (C4)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of fibroblast growth factor 19 (FGF19)		From baseline to Week 52 and up to a maximum of 6 years
Percentage of participants with no worsening of pruritus	Measured by the PBC Worst Itch Numeric Rating Scale (NRS)	From baseline to week 52 and up to a maximum of 6 years
Percentage of responders in PBC Worst Itch NRS	Defined as at least 30% reduction from baseline of NRS at week 52 in patients with a baseline NRS ≥ 4	Baseline through 52 weeks and up to a maximum of 6 years
Change from baseline in 5D-Itch	Change from baseline in symptoms in terms of 5 domains: degree, duration, direction, disability and distribution. Patients rate their symptoms over the preceding 2-week period on a 1 to 5 scale, with 5 being the most affected	From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a	Change from baseline in assessing seven items that measure both the experience of fatigue and the interference of fatigue on daily activities over the past week	From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in Epworth Sleepiness Scale (ESS)	Change from baseline in ESS that assesses eight 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 sleepiness, '3' indicates significant sleepiness).It provides a total score which has been shown to relate to the patient's level of daytime sleepiness (total score range 0-24 points).	From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in PBC-40	Assesses symptoms across six domains: fatigue, emotional and social, cognitive function, general symptoms and itch. Patients respond on a verbal response scale, depending on the section options range from 'never' / 'not at all' / 'strongly disagree' to 'always' / 'very much'/ 'strongly agree'. Five items (3/3 in the itch domain and 2/10 in the social domain) also include a 'does not apply' option. A score for each domain is provided (but a total score is not calculated), with each verbal response scale correlating to a score of 1-5 per item (0-5 on items with a 'does not apply' option) with 5 being the most affected. The PBC-40 has a 4-week recall period.	From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in health utility	Measured by Euro quality of life (EQ-5D-5L), a 6-item, standardized questionnaire that assesses mobility, self-care, usual activities, pain / discomfort, anxiety / depression, and overall health state	From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of type I collagen N-telopeptides (CTXI)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in levels of procollagen 1 N-terminal propeptide (P1NP)		From baseline to Week 52 and up to a maximum of 6 years
Change from baseline in bone mineral density (hip and lumbar) as assessed by DEXA scanning		From baseline to Week 52 and up to a maximum of 6 years
Percentage of patients with onset of clinical outcomes		From baseline to Week 52 and up to a maximum of 6 years
Number of participants experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs).	An Adverse event (AE) is any untoward medical occurrence, temporally associated with the use of study intervention, whether or not related to the study intervention. AESIs are AEs that may not be serious but are of special importance to a particular drug or class of drugs.	From baseline to Week 52 and up to a maximum of 6 years
Number of participants with clinically significant changes in physical examination	Percentage of participants with clinically significant changes in physical examination will be reported. The clinical significance will be graded by the investigator.	From baseline to Week 52 and up to a maximum of 6 years
Number of participants with clinically significant Changes in vital signs	Percentage of participants with clinically significant changes in Vital Signs will be reported. The clinical significance will be graded by the investigator.	From baseline to Week 52 and up to a maximum of 6 years
Number of participants with clinically significant changes in electrocardiogram (ECG)	Percentage of participants with clinically significant changes in ECG readings will be reported. The clinical significance will be graded by the investigator.	From baseline to Week 52 and up to a maximum of 6 years
Number of participants with clinically significant changes in laboratory parameters (blood chemistry and hematology)	Percentage of participants with clinically significant change in laboratory parameters (blood chemistry, hematology and coagulation) will be reported. The clinical significance will be graded by the investigator.	From baseline to Week 52 and up to a maximum of 6 years
Number of Participants With Clinically Significant Changes in liver markers		From baseline to Week 52 and up to a maximum of 6 years
Number of Participants With Clinically Significant Changes in Renal biomarkers (including urinalysis)		From baseline to Week 52 and up to a maximum of 6 years
Number of Participants With Clinically Significant Changes in other biochemical safety markers (e.g. urinary myoglobin)		From baseline to Week 52 and up to a maximum of 6 years
Area Under Curve steady state (AUCss) of study drug		After 4 weeks of treatment during the double-blind period
Pharmacokinetic (PK) Parameter: Clearance (CL) of study drug	Clearance (CL) is defined as the systemic clearance of the drug following oral administration.	After 4 weeks of treatment during the double-blind period
Pharmacokinetic (PK) Parameter: Vz of study drug	Vz is defined as the volume of distribution of the drug after oral administration.	After 4 weeks of treatment during the double-blind period

Collaborators and Investigators

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

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): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Primary Biliary Cholangitis; Elafibranor; PBC
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Cholangitis; Liver Cirrhosis, Biliary
• 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.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

• 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 EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• IPD Sharing Access Criteria: Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

Drug and device information, study documents

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