Primary Biliary Cholangitis (PBC)Phase 3ELFIDENCENCT06016842
A Long-Term Study of Elafibranor in Adult Participants With Primary Biliary Cholangitis
A Phase 3 study testing Elafibranor in people with Primary Biliary Cholangitis (PBC), run by Ipsen at 198 sites in 28 countries.
Trial summary
The participants of this study will have confirmed Primary Biliary Cholangitis (PBC) and cirrhosis (scarring of the liver). PBC is a slowly progressive disease, characterised by damage to the bile ducts in the liver, leading to a build-up of bile acids which causes further damage. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Biliary Cholangitis (PBC)
- What is being tested?
- Elafibranor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 276 participants
- Where
- 198 sitesin 28 countries
- Study dates
- 31 Aug 2023to 31 May 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants must be ≥18 years of age at the time of signing the informed consent.
- Participants with a definite or probable diagnosis of primary biliary cholangitis (PBC)
- Participants with cirrhosis at SV1. • Participants must be Child Pugh A or Child Pugh B.
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Who cannot join
- History or presence of other concomitant liver disease including but not limited to:
- i) Primary sclerosing cholangitis (PSC).
- ii) Autoimmune hepatitis (AIH) by simplified Diagnostic Criteria of the International Autoimmune Hepatitis Group (IAIHG) ≥6, or if treated for an overlap of PBC with AIH, or if there is clinical suspicion and evidence of overlap AIH features, that cannot be explained alone by insufficient response to UDCA.
- iii) Positive hepatitis B surface antigen (HBsAg). Participants with negative HBsAg and positive hepatitis B core antibody (HBcAb) may be eligible if hepatitis B virus deoxyribonucleic acid (HBV DNA) is negative.
- iv) Hepatitis C virus (HCV) infection defined by positive anti-HCV antibody and positive HCV ribonucleic acid (RNA) (Note: Participants with positive anti-HCV antibody due to previously treated HCV infection, may be enrolled if a confirmatory HCV RNA is undetectable and sustained viral response has been documented).
- v) Alcohol-associated liver disease (ALD).
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- vi) Nonalcoholic steatohepatitis (NASH).
- vii) Other chronic liver diseases, such as alpha-1 antitrypsin deficiency.
- History or presence of clinically significant hepatic decompensation, including:
- i) History of liver transplantation, current placement on a liver transplant list, current model for end-stage liver disease including (MELD) 3.0 score >12 due to hepatic impairment.
- ii) Evidence of complications of cirrhosis, including hepatic decompensation or evidence of significant portal hypertension complications including presence of uncontrolled ascites; history of variceal bleeding or related interventions (e.g. variceal banding, or transjugular intrahepatic portosystemic shunt placement); presence of hepatic encephalopathy Grade 2 or higher per West-Haven criteria; history or presence of spontaneous bacterial peritonitis. Note: participants with low-risk varices (Grade I) without history of bleeding or other treatment may be eligible to enrol.
- iii) Hepatorenal syndrome (HRS) (type I or II ). • vi) Hospitalisation for liver-related complication within 12 weeks prior to SV1.
- Known history of human immunodeficiency virus (HIV) infection or having a positive confirmatory test for HIV type 1 or 2.
- Medical conditions that may cause non-hepatic increases in ALP (e.g. Paget's disease).
- Evidence of any other unstable or untreated clinically significant immunological, endocrine, hematologic, gastrointestinal, neurological, or psychiatric disease as evaluated by the investigator; other clinically significant conditions that are not well controlled.
- Non-hepatic medical conditions that may diminish life expectancy to <2 years, including known cancers.
- History of hepatocellular carcinoma.
- Alpha-fetoprotein (AFP) >20 ng/mL with 4-phase liver computerised tomography (CT) or magnetic resonance imaging (MRI) imaging suggesting presence of hepatocellular carcinoma.
- Known malignancy or history of malignancy within the last 5 years. Participants with non-melanoma skin cancer, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Administration of the following medications is prohibited during the study, and prior to the study as per the timelines specified below: • i) 3 months prior to baseline: fibrates, seladelpar, glitazones, obeticholic acid, 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).
- Participants who are currently participating in, plan to participate in, or have participated in an investigational drug study or medical device study containing active substance within 30 days or 5 half-lives, whichever is longer, prior to the screening period.
- If the previous study was for an experimental therapy being studied for potential benefit in PBC, and the potential therapeutic agent was proven to have no beneficial effect in PBC and there are no safety concerns, the participant may enrol after 30 days or 5 half-lives from the last dose of the therapeutic agent, whichever is longer.ii) For therapeutic agents being studied for potential benefit in PBC for which it is still unclear if there may be a potential benefit, participants may enrol after 6 months from the last dose of the therapeutic agent.
- Electrocardiogram (ECG) with QT interval corrected by Fridericia's formula (QTcF) >450 msec in males or QTcF >470 msec in females for participants without bundle branch block. For participants with bundle branch block or other intraventricular conduction delay, a longer QTcF >480 msec would be exclusionary.
- Total bilirubin (TB) >5x ULN
- Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >5x ULN at SV1
- Creatinine phosphokinase (CPK) >2x ULN.
- Platelet count <50,000/μL
- International normalised ratio (INR) >1.8 in the absence of anticoagulant therapy.
- Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m2 per the Modification of Diet in Renal Disease (MDRD)-6 Study formula at SV1.
- Significant renal disease, including nephritic syndrome, chronic kidney disease (CKD) (defined as participants with evidence of significantly impaired kidney function or underlying kidney injury).
- For female participants: known current pregnancy, or has a positive serum pregnancy test, or is breastfeeding.
- Participants unwilling or unable to be abstinent from alcohol during the study.
- History of alcohol abuse, or other substance abuse within 1 year prior to SV1.
- Known hypersensitivity to elafibranor or to any of the excipients of the investigational product(s).
- Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.
- Any other condition that, in the opinion of the investigator, would interfere with study participation or completion, or would put the participant at risk, including a potential participant assessed as being at high risk of noncompliance with the study.
- Alkaline phosphatase (ALP) ≥10x ULN.
- Albumin <2.8 g/dL due to impaired hepatic function.
Trial locations and contacts
198 sites in 28 countries. Contact the study team or a site near you to ask about taking part.
198 sites in 28 countries
United States43 sites, 29 recruiting
- Terminated
Southwest Gastroenterology Associates, PC (SWGA)
Albuquerque, New Mexico, 87109
- Recruiting
University of Michigan Health System
Ann Arbor, Michigan, 48109
- Recruiting
Texas Clinical Research Institute
Arlington, Texas, 22201
- Recruiting
University of Colorado
Aurora, Colorado, 80045
- Recruiting
American Research Corporation
Austin, Texas, 78757
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
- Recruiting
University of Virginia Medical Center
Charlottesville, Virginia, 22903
- Recruiting
Peak Gastroenterology Associates
Colorado Springs, Colorado, 80829
- Withdrawn
Medstar Georgetown Transplant Institute University Hospital (MGUH)
Columbia, Washington, 20007
- Recruiting
Gastroenterology Center of the Midsouth
Cordova, Tennessee, 38138
- Recruiting
Southern California Research Center
Coronado, California, 92118
- Withdrawn
Rush University Medical Center - University Cardiovascular Surgeons
Dallas, Texas, 60612
- Terminated
Liver Center of Texas
Dallas, Texas, 75203
- Recruiting
Methodist Transplant Physicians
Dallas, Texas, 75203
- Recruiting
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390
- Active, not recruiting
South Denver Gastroenterology, P.C.
Englewood, Colorado, 80113
- Withdrawn
Baylor Scott & White All Saints Medical Center - Forth Worth
Fort Worth, Texas, 76104
- Recruiting
Liver Associates of Texas
Houston, Texas, 77030
- Active, not recruiting
Houston Methodist Cancer Center
Houston, Texas, 77584
- Recruiting
University Physicians and Surgeons Inc, dba Marshall Health
Huntington, West Virginia, 25701
- Not yet recruiting
University of Kansas Medical Center (KUMC) - University of Kansas Liver Center - Hepatology Clinic
Kansas City, Kansas, 66160
- Terminated
Gastro health & Nutrition
Katy, Texas, 77904
- Terminated
Arkansas Diagnostic Center, PA
Little Rock, Arkansas, 55130
- Recruiting
Rocky Mountain Gastroenterology
Littleton, Colorado, 80120
- Withdrawn
Cedars-Sinai Medical Center
Los Angeles, California, 90048
- Active, not recruiting
GastroIntestinal BioSciences
Los Angeles, California, 90067
- Withdrawn
University of California Los Angeles
Los Angeles, California, 90404
- Recruiting
University Of Miami School Of Medicine, Center For Liver Diseases
Miami, Florida, 33136
- Recruiting
NYU Langone Gastroenterology and Hepatology Associates
New York, New York, 10016
- Recruiting
Bolanos Clinical Research
Pembroke Pines, Florida, 12105
- Recruiting
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
- Recruiting
Bon Secours St. Mary's Hospital of Richmond, Inc
Richmond, Virginia, 23226
- Not yet recruiting
Virginia Commonwealth University Medical Center - West Hospital
Richmond, Virginia, 23298
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
- Recruiting
University of California Davis Medical Center
Sacramento, California, 95817
- Recruiting
American Research Corporation at The Texas Liver Institute
San Antonio, Texas, 78015
- Recruiting
Starhope Liver Center, PA - Starhope Clinical Research, LLC
San Antonio, Texas, 78251
- Recruiting
Velocity Clinical Research at Liver Institute Northwest
Seattle, Washington, 98105
- Recruiting
Louisiana Research Center, LLC
Shreveport, Louisiana, 71103
- Recruiting
International Center for Research
Tampa, Florida, 33614
- Recruiting
Arizona Liver Health
Tucson, Arizona, 85641
- Withdrawn
Impact Research Tx
Waco, Texas, 76710
- Withdrawn
Huron Gastroenterology Associates - Center for Digestive Care
Ypsilanti, Michigan, 48197
South Korea20 sites, 15 recruiting
- Recruiting
Soon Chun Hyang University Bucheon Hospital
Bucheon-si
- Recruiting
Pusan National University Hospital (PNUH)
Busan
- Recruiting
Keimyung University Dongsan Hospital
Daegu
- Withdrawn
The Catholic University of Korea Daejeon St.Mary's Hospital
Daejeon
- Recruiting
Inje University Ilsan Paik Hospital
Goyang-si
- Withdrawn
Korea University Ansan Hospital
Gyeonggi-do
- Recruiting
Inha University Hospital
Incheon
- Recruiting
Kyungpook National University Hospital (KNUH)
Junggu
- Recruiting
CHA Bundang Medical Center, CHA University
Seongnam-si
- Withdrawn
Chung-Ang University Hospital
Seoul
- Withdrawn
Hallym University Kangnam Sacred Heart Hospital
Seoul
- Recruiting
Hanyang University Seoul Hospital
Seoul
- Recruiting
Korea University Guro Hospital
Seoul
- Recruiting
Samsung Medical Center
Seoul
- Recruiting
Seoul National University Bundang Hospital (SNUBH)
Seoul
- Recruiting
Seoul National University Hospital
Seoul
- Terminated
Severance Hospital, Yonsei University Health System
Seoul
- Recruiting
The Catholic University of Korea, Eunpyeong St. Mary's Hospital
Seoul
- Recruiting
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul
- Recruiting
The Catholic University of Korea, Uijeongbu St. Mary's Hospital
Uijeongbu-si
Poland13 sites, 11 recruiting
- Recruiting
NZOZ Twoje Zdrowie EL Sp. z o.o.
Elblag
- Recruiting
Uniwersyteckie Centrum Kliniczne im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego
Katowice
- Recruiting
Krakowskie Centrum Medyczne Sp.z.o.o - FutureMeds
Krakow
- Withdrawn
Szpital Uniwersytecki w Krakowie
Krakow
- Recruiting
Oddzial Kliniczny Gastroenterologii Ogolnej i Onkologicznej SPZOZ, Uniwersytecki Szpital Kliniczny im. Barlickiego w Lodzi
Lodz, 90-153
- Recruiting
Medrise Sp. z o.o.
Lublin
- Not yet recruiting
Krakowskie Centrum Medyczne Sp.z.o.o. - FutureMeds
Małogoskie
- Recruiting
Centrum Medyczne Medyk Sp. z o.o. Sp. K.
Rzeszów
- Withdrawn
Niepubliczny Zaklad Opieki Zdrowotnej (NZOZ) - Poliklinika Doktora Bessera
Sosnowiec
- Recruiting
FutureMeds Warszawa Centrum
Warsaw
- Recruiting
FutureMeds sp. z o. o
Wroclaw
- Recruiting
Nzoz Centrum BadanKlinicznych
Wroclaw
- Recruiting
PlanetMed Sp. z o.o.
Wroclaw
Spain13 sites, 8 recruiting
- Recruiting
Hospital Clinic i Provincial de Barcelona
Barcelona
- Recruiting
Hospital Universitario Vall d'Hebron
Barcelona
- Recruiting
Clinica Universidad Navarra-Sede Madrid
Madrid
- Active, not recruiting
Hospital General Universitario Gregorio Maranon (HGUGM)
Madrid
- Withdrawn
Hospital Universitario La Paz
Madrid
- Recruiting
Hospital Universitario Puerta de Hierro de Majadahonda
Majadahonda
- Recruiting
Hospital Universitario Virgen de la Victoria
Málaga
- Recruiting
Hospital De Montecelo
Pontevedra
- Active, not recruiting
Institut d Investigacio i Innovacio Parc Tauli, Hospital Universitari Parc Tauli
Sabadell
- Recruiting
Hospital Universitario Virgen del Rocio
Seville
- Terminated
Hospital Universitario y Politecnico La Fe
Valencia, 46026
- Withdrawn
Hospital Universitario Rio Hortega
Valladolid
- Recruiting
Hospital Universitario Miguel Servet
Zaragoza
France10 sites, 5 recruiting
- Recruiting
Hopital Beaujon
Clichy
- Recruiting
Hospital Henri Mondor
Créteil, 94000
- Withdrawn
Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez
Lille
- Recruiting
Hospices Civils de Lyon (HCL) - Hopital de la Croix-Rousse
Lyon
- Withdrawn
Hopital Saint Joseph - Marseille
Marseille
- Recruiting
CHU de Nice, Hopital de l'Archet
Nice
- Recruiting
Hopital Pitie-Salpetriere - APHP
Paris, 75013
- Withdrawn
CHU Poitiers
Poitiers
- Withdrawn
Clinique Pasteur
Toulouse
- Withdrawn
Hopital Paul-Brousse - APHP
Villejuif
Argentina8 sites, 7 recruiting
- Recruiting
DIM Centro Medico
Buenos Aires
- Recruiting
Fundacion Respirar (Centro Medico Dra. De Salvo) - Instituto Argentino de Investigaciones Clinicas (IAIC) S.R.L
Buenos Aires
- Recruiting
Hospital Britanico de Buenos Aires
Buenos Aires
- Recruiting
Hospital Italiano de Buenos Aires
Buenos Aires
- Recruiting
Centro Medico Colon
Córdoba
- Withdrawn
Hospital Espanol de Mendoza
Mendoza
- Recruiting
Hospital Universitario Austral
Pilar
- Recruiting
Hospital El Cruce
San Juan Bautista
Italy8 sites
- Withdrawn
Azienda Ospedaliero Universitaria Modena
Modena
- Active, not recruiting
Ospedale San Gerardo
Monza
- Terminated
Azienda Ospedaliero Universitaria Federico II di Napoli
Naples
- Withdrawn
Azienda Ospedaliera di Padova - U.O.C. di Gastroenterologia
Padova
- Terminated
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Palermo
- Withdrawn
Fondazione I.R.C.C.S. Policlinico San Matteo
Pavia
- Withdrawn
Azienda Ospedaliero Universitaria Pisana
Pisa
- Withdrawn
Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo
Brazil7 sites, 7 recruiting
- Recruiting
NUPEC Cardio
Belo Horizonte
- Recruiting
Universidade Federal de Goias
Goiânia
- Recruiting
Hospital de Clinicas de Porto Alegre (HCPA)
Porto Alegre
- Recruiting
Instituto D'Or de Pesquisa e Ensino - Hospital Aliança
Salvador
- Recruiting
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
São Paulo
- Recruiting
Hospital de Base - Centro Integrado de Pesquisa ( CIP )
São Paulo
- Recruiting
Universidade Estadual Paulista Julio De Mesquita Filho (UNESP) Hospital das Clinicas Faculdade de Medicina de Botucatu (HCFMB)
São Paulo
Israel7 sites
- Withdrawn
Institute of Gastroenterology and Liver Diseases - Soroka University Medical Center
Beersheba
- Withdrawn
Rambam Health Care Campus (RHCC)
Haifa
- Terminated
Hadassah University Hospital (HUH) - Ein-Kerem
Jerusalem
- Terminated
Shaare Zedek Medical Center
Jerusalem
- Withdrawn
Galilee Medical Center, ZIV Medical Center
Nahariya
- Terminated
Galilee Medical Center
Nahariya
- Withdrawn
Rabin Medical Center - Beilinson Hospital - Liver Institute
Petah Tikva
Australia6 sites, 3 recruiting
- Recruiting
Sunshine Coast University Hospital
Birtinya
- Recruiting
Footscray Hospital, Western Health
Footscray
- Withdrawn
Nepean Clinical School
Kingswood
- Withdrawn
Monash University - Monash Health -Monash Medical Centre
Melbourne
- Withdrawn
St George Hospital
Sydney
- Recruiting
Westmead Hospital
Westmead
Chile6 sites, 6 recruiting
- Recruiting
Universidad De Los Andes
Las Condes
- Recruiting
Centro de Estudios Clinicos e Investigaciones Medicas (CECIM)
Santiago
- Recruiting
Enroll SpA
Santiago
- Recruiting
Hospital Clinico de la Pontificia Universidad Catolica de Chile
Santiago
- Recruiting
University of Chile Clinical Hospital (Hospital Clinico de la Universidad de Chile)
Santiago
- Recruiting
Centro Medico Cedid - Centro de Diagnostico Digestivo
Viña del Mar
Colombia6 sites, 6 recruiting
- Recruiting
Clinica de la Costa
Barranquilla
- Recruiting
Clinica Imbanaco de S.A.S.
Cali
- Recruiting
Salud SURA Chipichape
Cali
- Recruiting
Fundacion Oftalmologica de Santander-Clinica Ardila Lulle La FOSCAL
Floridablanca
- Recruiting
Hospital Pablo Tobon Uribe
Medellín
- Recruiting
Servicios de Salud IPS Suramericana S.A.S. Industriales
Medellín
Mexico6 sites, 6 recruiting
- Recruiting
Centro de Investigacion Clinica y Medicina Traslacional
Guadalajara
- Recruiting
Centro de Investigacion Medico Biologica y Terapia Avanzada
Jalisco
- Recruiting
Centro de Investigacion y Gastroenterologia SC
Mexico City
- Recruiting
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (INCMNSZ)
Mexico City
- Recruiting
Hospital Angeles Valle Oriente
Monterrey
- Recruiting
Medical Care & Research
Yucatán
Romania6 sites, 6 recruiting
- Recruiting
Centrul Pentru Studiul Metabolismului
Bucharest
- Recruiting
Sana S.R.L
Bucharest
- Recruiting
Spital Clinic Dr I Cantacuzino
Bucharest
- Recruiting
Cluj County Clinical Emergency Hospital
Cluj-Napoca
- Recruiting
Spitalul Clinic De Urgenta Prof. Dr. Octavian Fodor
Cluj-Napoca
- Recruiting
Gastromedica Srl
Iași, 700111
Czechia5 sites, 4 recruiting
- Recruiting
Hepato-Gastroenterologie HK, s.r.o.
Hradec Králové
- Withdrawn
Krajska Nemocnice Liberec
Liberec
- Recruiting
Artroscan
Ostrava
- Recruiting
Research Site s.r.o.
Pilsen
- Recruiting
Institute for Clinical and Experimental Medicine - IKEM
Prague
Belgium4 sites, 1 recruiting
- Withdrawn
Universitair Ziekenhuis Antwerpen
Edegem
- Withdrawn
Ziekenhuis Oost-Limburg
Genk
- Recruiting
Gent University Hospital
Ghent
- Withdrawn
Algemeen Ziekenhuis Delta
Roeselare
Greece4 sites, 4 recruiting
- Recruiting
Agios Savvas Regional Cancer Hospital
Athens
- Recruiting
General Hospital of Athens Laiko
Athens
- Recruiting
General Oncological Hospital of Kifisia Oi Agioi Anargyroi
Athens
- Recruiting
GeneIppokratio General Hospital of Thessaloniki
Thessaloniki
Bulgaria3 sites, 2 recruiting
- Active, not recruiting
Diagnostic-Consultative Center Aleksandrovska EOOD
Sofia
- Recruiting
Tokuda Hospital, Dept. of Internal Medicine
Sofia
- Recruiting
University Hospital City Clinic Cancer Center
Sofia
Hungary3 sites, 3 recruiting
- Recruiting
Central Hospital of Northern Pest - Military Hospital
Budapest
- Recruiting
Kenezy County Hospital
Debrecen
- Recruiting
Szegedi Tudomanyegyetem AOK, I. sz Belgyogyaszati Klinika
Szeged
Malaysia3 sites, 3 recruiting
- Recruiting
Hospital Sultanah Aminah
Johor Bahru
- Recruiting
Hospital Queen Elizabeth II
Kota Kinabalu
- Recruiting
University of Malaya Medical Centre
Kuala Lumpur
Portugal3 sites, 3 recruiting
- Recruiting
Hospitais da Universidade de Coimbra (H.U.C) - Universidade de Coimbra
Coimbra, Praceta Mota Pinto
- Recruiting
Hospital Dr. Nelio Mendonca
Funchal, 9004-514
- Recruiting
Unidade Local de Saúde de Trás-os-Montes e Alto Douro, E. P. E
Vila Real, 5000-508
Slovakia3 sites, 3 recruiting
- Recruiting
Gastroenterological Centre Thalion
Bratislava
- Recruiting
Univerzitna nemocnica L. Pasteura Kosice
Košice
- Recruiting
Fakultna nemocnica Nitra
Nitra
Thailand3 sites, 3 recruiting
- Recruiting
Chiang Mai University
Chiang Mai
- Recruiting
Prince of Songkla University (PSU) - Songklanagarind Hospital
Hat Yai
- Recruiting
Srinagarind Hospital - Khon Kaen University
Khon Kaen
Canada2 sites, 2 recruiting
- Recruiting
University of Alberta - Faculty of Medicine & Dentistry - The Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR)
Edmonton
- Recruiting
University Health Network (UHN) - Toronto General Hospital (TGH) - Toronto General Research Institute (TGRI)
Toronto
Lithuania2 sites, 2 recruiting
- Recruiting
Hospital of Lithuanian University of Health Sciences Kaunas
Kaunas
- Recruiting
Vilnius University Hospital Santaros Klinikos
Vilnius
New Zealand2 sites, 2 recruiting
- Recruiting
Canterbury District Health Board
Christchurch
- Recruiting
Waikato Hospital
Hamilton
About this study
Official title: A Phase III Randomised, Parallel-Group, Double-Blind, Placebo-Controlled, Two-Arm Study to Evaluate the Efficacy and Safety of Elafibranor 80 mg on Long-Term Clinical Outcomes in Adult Participants With Primary Biliary Cholangitis (PBC)
The participants of this study will have confirmed Primary Biliary Cholangitis (PBC) and cirrhosis (scarring of the liver).
PBC is a slowly progressive disease, characterised by damage to the bile ducts in the liver, leading to a build-up of bile acids which causes further damage.
Read more
The liver damage in PBC may lead to 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 will compare a daily dose of elafibranor (the study drug) to a daily dose of placebo (a dummy treatment) and will last up to 3.5 years for each participant.
The main aim of this study is to determine if elafibranor is better than placebo in preventing clinical outcome events showing disease worsening (including progression of disease leading to liver transplant or death).
This study will also study the safety of long-term treatment with elafibranor, as well as the impact on symptoms such as itching and tiredness.
- Conditions
- Primary Biliary Cholangitis (PBC)
- Being tested
- Elafibranor, Matched 80 mg placebo
- Medical subject headings
- Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ElafibranorDrug
Duration: up to an estimated 42-month (3.5-year) double-blind treatment period during which elafibranor 80 mg tablet will be administered once daily
Matched 80 mg placeboOther
Duration: up to an estimated 42-month (3.5-year) double-blind treatment period during which matching placebo tablet will be administered once daily
| Study group | Role | What they receive |
|---|---|---|
| Elafibranor 80 mg | Experimental | Participants will take 1 tablet of elafibranor 80 mg per day orally with a glass of water at approximately the same time each morning, with or without food. Receives: Drug: Elafibranor |
| Placebo | Placebo comparator | Participants will take 1 placebo tablet per day orally (matching the 80 mg elafibranor sized tablet) with a glass of water at approximately the same time each morning, with or without food. Receives: Other: Matched 80 mg placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival
Event-free survival is defined as the time from randomisation to either adjudicated disease progression or death, whichever occurs first.
Measured: From baseline until 4 weeks after the last dose of study intervention (maximum duration of 3.5 years)
Secondary outcomes (59)
Percentage of participants experiencing Treatment Emergent Adverse Events (TEAEs), treatment-related TEAEs, Serious Adverse Events (SAEs), and Adverse Events of Special Interests (AESIs)
An adverse event (AE) is any unfavourable medical occurrence in a trial participant administered the investigational product. The AE does not necessarily have a causal relationship with the treatment. AESIs are AEs that may or may not be serious but are of special importance to a particular drug or class of drugs.
Measured: From baseline until 4 weeks after the last dose of study intervention (maximum duration of 3.5 years)
Percentage of participants developing clinically significant changes in physical examination findings
Complete physical examination at screening and targeted examination at all other clinical visit timepoints.
Measured: From baseline until 4 weeks after the last dose of study intervention (maximum duration of 3.5 years)
Percentage of participants developing 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.
Measured: From baseline until 4 weeks after the last dose of study intervention (maximum duration of 3.5 years)
Percentage of participants developing clinically significant changes in Electrocardiogram (ECG) readings.
Percentage of participants with clinically significant changes in ECG readings will be reported. The clinical significance will be graded by the investigator.
Measured: From baseline until 4 weeks after the last dose of study intervention (maximum duration of 3.5 years)
Percentage of participants with clinically significant changes in laboratory parameters (blood chemistry, hematology, coagulation and urinalysis)
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.
Measured: From baseline until 4 weeks after the last dose of study intervention (maximum duration of 3.5 years)
Change from baseline in Alkaline phosphatase (ALP)
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in Total Bilirubin (TB)
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with ALP≤ 1.67x ULN and TB≤ ULN
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with complete biochemical response
Defined as normal levels of TB, ALP, transaminases, albumin, and International normalised ratio (INR)
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with normalisation of TB and ALP
Defined as TB< Upper Limit Normal (ULN) and ALP< ULN
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with stabilisation in TB (i.e. no increase)
Defined as TB< 1x ULN or increase from baseline <0.1x ULN
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with a response based on albumin normalisation
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in liver stiffness measurement (LSM)
Assessed by vibration-controlled transient elastography (VCTE) using Fibroscan® on the day of the visit.
Measured: At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in PBC risk scores based in Global PBC Study Group (GLOBE) score
The GLOBE score is a validated risk assessment tool providing an estimate of transplant-free survival for patients with PBC. It was developed by the Global PBC Study Group using Cox regression model on over 4,000 patients with PBC. Lower GLOBE score predicts lower risk. It is calculated from the following equation:
GLOBE score = (0.044378 * age + 0.93982 * LN(total bilirubin/ULN) +(0.335648 * LN(alkaline phosphatase/ULN)) - 2.266708 * albumin /LLN -0.002581 * platelet count per 109/L) + 1.216865
GLOBE scoring system, which calculation is based on serum values of bilirubin, ALP, albumin and platelet count after 1 year of treatment and age at baseline. A high number is indicative of a worse score.
Measured: At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in PBC risk scores based on United Kingdom (UK)-PBC score.
PBC risk score developed by United Kingdom (UK)-PBC Consortium is a scoring system and the calculation is based on laboratory test measurements and upper limits of normal (ULN) for the total bilirubin (BIL12); alanine transaminase or aspartate transaminase (TA12), and alkaline phosphatase (ALP12) after at least 12 months of UDCA, and the laboratory test measurements and lower limits of normal (LLN) for the serum albumin and platelet count in the same timeframe. A high number is indicative of a worse score.
Measured: At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with LSM ≥15 kPa
Assessed by VCTE using Fibroscan®
Measured: At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change in serum levels of Aspartate aminotransferase (AST) compared to the baseline
Measured: At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change in serum levels of ALT compared to the baseline
Measured: At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change in serum levels of Gamma-glutamyl transferase (GGT) compared to the baseline
Measured: At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in hepatic function: Conjugated (direct) bilirubin
Measured: At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change in serum levels of Albumin compared to the baseline
Measured: At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in hepatic function: international normalised ratio (INR)
Measured: At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in hepatic function: fractionated ALP
Measured: At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with no worsening of LSM
Assessed by VCTE using Fibroscan® defined as no increase >2kPa from baseline
Measured: At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with ALP reduction of 40%
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with ALP reduction >40% or ALP normalisation (Barcelona criteria)
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with ALP <1.5x ULN, ALP decrease ≥15% and TB ≤ULN
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with ALP <1.5x ULN, ALP decrease ≥40% and TB ≤ULN
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with ALP <1.67x ULN, ALP decrease ≥15% and TB ≤ULN
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with ALP <3x ULN, AST <2x ULN and TB ≤1 mg/dL (Paris I)
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with ALP ≤1.5x ULN, AST ≤1.5x ULN and TB ≤1 mg/dL (Paris II criteria)
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with normalisation of abnormal TB
Measured: Assessed at Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with normalisation of abnormal TB and albumin (Rotterdam criteria)
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with TB ≤0.6× ULN in participants with TB >0.6× ULN at baseline
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in lipid parameters: total cholesterol (TC)
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in lipid parameters: high density lipoprotein cholesterol (HDL-C)
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in lipid parameters: calculated very low density lipoprotein cholesterol (VLDL-C)
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in lipid parameters: low density lipoprotein cholesterol (LDL-C)
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in lipid parameters: triglycerides (TG)
Measured: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with a response in PBC Worst Itch NRS score
Defined as ≥2-point reduction from baseline NRS in participants with a baseline NRS ≥4
Measured: Through 6 months up to end of treatment (maximum duration of 3.5 years)
Percentage of participants with a response in PBC Worst Itch NRS
Defined as ≥3-point reduction from baseline NRS in participants with a baseline NRS ≥4
Measured: Assessed through 6 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in 5D-Itch scale
Questionnaire that assesses symptoms in terms of 5 domains: degree, duration, direction, disability and distribution. Participants rate their symptoms over the preceding 2-week period on a 1 to 5 scale, with 5 being the most affected.
Measured: Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in Patient Global Impression of Severity (PGI-S)
A 1-item, 5-point scale designed to assess the participant's impression of disease severity
Measured: Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)
Patient Global Impression of Change (PGI-C)
A 1-item, 5-point scale designed to assess the participant's impression of change in disease severity since the baseline visit
Measured: Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form 7a
Consists of 7 items that measure both the experience of fatigue and the interference of fatigue on daily activities over the past week. Response options are on a 5-point Likert scale, ranging from 1 to 5. Scores can range from 7 to 35, with higher scores indicating greater fatigue.
Measured: Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in the Epworth Sleepiness Scale (ESS)
Self-administered questionnaire that consists of 8 questions asking to rate how likely it is to fall asleep in different situations commonly encountered in daily life (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 participant's level of daytime sleepiness (total score range 0-24 points).
Measured: Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in PBC-40 score
40-item questionnaire that assesses symptoms across 6 domains: fatigue, emotional and social, cognitive function, general symptoms and itch. Participants 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'. Six items (3/3 in the itch domain, 2/10 in the social domain, and 1/7 in the general symptoms 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 to 5 per item (0 to 5 on items with a 'does not apply' option) with 5 being the most affected (greatest burden). The PBC-40 has a 4-week recall period.
Measured: Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in PBC Worst Itch Numeric Rating Scale (NRS) score
Self-administered patient-reported outcome questionnaire that measures itch intensity. It asks participants to rate the intensity of their Worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (Worst Itch imaginable): - once daily (24-hour recall period) using the eDiary during the screening and initial 2 years of the study, - at the clinic visits (7-day recall period), from Year 3 onwards
Measured: Assessed through 6 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in EuroQol 5-dimensional 5-level questionnaire (EQ-5D-5L)
Self-administered standardised questionnaire that assesses the 5-dimensions of mobility, self-care, usual activities, pain/discomfort, anxiety/depression descriptively (each dimension has 5 levels) and the overall health state via an EQ Visual Analogue Scale (VAS).
Measured: Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)
Change from baseline in Work Productivity and Activity Impairment General Health (WPAI-GH)
Questionnaire that measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. It consists of 6 questions: 1=currently employed; 2=hours missed because of health problems; 3=hours missed because of other reasons; 4=hours actually worked; 5=degree health affected productivity while working (using a 0 to 10 Visual Analogue Scale (VAS)); 6=degree health affected productivity in regular unpaid activities (VAS).
Measured: Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)
Time to the first occurrence of each of individual adjudicated clinical outcome events
Among: • All-cause mortality • Liver-related mortality • Liver transplant • MELD-3.0 score ≥15 in participants with baseline MELD score ≤12 • Liver decompensation
Measured: From baseline until 4 weeks after the last dose of study intervention
Percentage of participants who experience any subsequent adjudicated clinical outcome events after the first occurrence of such an event
Among: • All-cause mortality • Liver-related mortality • Liver transplant • MELD-3.0 score ≥15 in participants with baseline MELD score ≤12 • Liver decompensation
Measured: From baseline until 4 weeks after the last dose of study intervention
Area under the plasma concentration-time curve from time 0 to 24 hours: AUC0-24
Measured: At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
Maximum (peak) plasma drug concentration: Cmax
Measured: At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
Time to reach maximum (peak) plasma concentration following drug administration): Tmax
Measured: At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
Apparent clearance of drug from plasma (CL)
Measured: At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
Apparent volume of distribution (VZ)
Measured: At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
Change from baseline in model for end-stage liver disease (MELD) 3.0 score
The MELD 3.0 score is calculated from parameters (sex, creatinine, bilirubin, INR, sodium and albumin) where a high score indicates a greater risk of needing a liver transplant.
Measured: From screening until end of treatment (maximum duration of 3.5 years)
Change from baseline in Child Pugh grade
Child Pugh grade is calculated using bilirubin, albumin, INR, ascites and encephalopathy.
A high grade is indicative of worse liver disease.
Measured: From screening until end of treatment (maximum duration of 3.5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2023
- Study start31 Aug 2023
- Primary completion31 May 2029 (estimated)
- Study completion31 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Biliary Cholangitis (PBC)Studies of the same condition, open and under way.
- More trials run by IpsenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 276 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ipsen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ipsen Medical Director, Study director, Ipsen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06016842
- Sponsor's protocol ID
- CLIN-60190-454
- Other IDs
- 2023-505251-43-00, 2023
- Acronym
- ELFIDENCE
- Status last verified
- Oct 2026
- First submitted
- 22 Aug 2023
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.