A Study to Assess Safety and Effectiveness of Elafibranor in Adult Participants With Primary Sclerosing Cholangitis.

NCT ID: NCT05627362

Last Updated: 2025-12-31

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-29
• Study Completion Date: 2026-08-28

Brief Summary

This study will evaluate the effects of elafibranor (the study drug) in participants with Primary Sclerosing Cholangitis (PSC). PSC is a rare disease of the liver that leads to injury and destruction of bile ducts. Damage to bile ducts leads to buildup of bile in the liver, which then causes further damage, and leads to disease progression. This study will compare elafibranor to a placebo, a dummy treatment. The main objective of the trial will be to study the safety and side effects of the study drug. The trial will also study the study drug's effects on blood tests and other tests related to PSC disease activity.

Conditions

Primary Sclerosing Cholangitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Double-Blind Period: Elafibranor 80 mg

Participant will receive two tablets per day (one tablet of elafibranor 80 mg + 1 tablet of placebo matching the 120 mg sized tablet) over the 12 weeks in Double-blind period.

Group Type: EXPERIMENTAL

Elafibranor 80 mg

Intervention Type: DRUG

Oral Tablet

Placebo Matched to Elafibranor 120 mg

Intervention Type: DRUG

Oral Tablet

Double-Blind Period: Elafibranor 120 mg

Participant will receive 2 tablets per day (one tablet of elafibranor 120 mg + 1 tablet of placebo matching the 80 mg sized tablet) over the 12 weeks in Double-blind period.

Group Type: EXPERIMENTAL

Elafibranor 120 mg

Intervention Type: DRUG

Oral Tablet

Placebo Matched to Elafibranor 80 mg

Intervention Type: DRUG

Oral Tablet

Double-Blind Period: Placebo

Participant will receive 2 placebo tablets per day (one matching the 80 mg sized tablet + one matching the 120 mg sized tablet) over the 12 weeks in Double-blind period.

Group Type: PLACEBO_COMPARATOR

Placebo Matched to Elafibranor 80 mg

Intervention Type: DRUG

Oral Tablet

Open-Label Extension Period: Elafibranor 120 mg

Participant will receive one tablet per day (elafibranor 120 mg) over the 96 weeks in Open-Label extension period.

Group Type: EXPERIMENTAL

Elafibranor 120 mg

Intervention Type: DRUG

Oral Tablet

Interventions

Elafibranor 80 mg

Oral Tablet

Intervention Type: DRUG

Elafibranor 120 mg

Oral Tablet

Intervention Type: DRUG

Placebo Matched to Elafibranor 80 mg

Oral Tablet

Intervention Type: DRUG

Placebo Matched to Elafibranor 120 mg

Oral Tablet

Intervention Type: DRUG

Other Intervention Names

GFT505; GFT505

Eligibility Criteria

Inclusion Criteria

• Participants with a diagnosis of Primary sclerosing cholangitis (PSC) as demonstrated by the presence of the following, and in the absence of apparent causes of secondary sclerosing cholangitis: i) Historical evidence of an elevated Alkaline phosphatase (ALP) > Upper Limit Normal (ULN) since at least 6 months prior to SV1. ii) Cholangiogram (e.g. magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangiography (PTC) with features compatible with large duct PSC.
• ALP ≥1.5x ULN during screening (with variability ≤30% based on two values).
• Total bilirubin ≤2.0x ULN at Screening Visit 1(SV1)
• Participants taking ursodeoxycholic acid (UDCA) at a total daily dose ≤23 mg/kg/day, with a minimum of 6 months of stable treatment prior to screening period and expected to remain on stable dose through the 12-week DBP. Minimum of 3 months off treatment prior to screening period if UDCA was recently discontinued.
• For participants with Inflammatory bowel disease (IBD): i) Participants with Crohn's disease must be in remission based on the investigator's clinical assessment and should be on stable treatment prior to randomisation and during screening. ii) Participants with ulcerative colitis must be in remission or have low activity disease as per the judgement of the investigator and should be on stable treatment prior to randomisation and during screening. iii) Current treatment for IBD is permitted, if the participant has been well controlled for ≥3 months prior to the screening period and is anticipated to remain on a stable dose of drugs for IBD treatment, including biologics, immunosuppressants, immunomodulators, or systemic corticosteroids. iv) Participants with IBD should have a colonoscopy performed within one year prior to the screening period showing no evidence of dysplasia or cancer.
• Medications for management of pruritus (e.g. cholestyramine, rifampin, naltrexone or sertraline) must be on a stable dose for ≥3 months prior to the screening period.
• Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. -A female participant is eligible to participate if she is not pregnant or breastfeeding at screening, is willing not to become pregnant during the study and is willing to follow applicable protocol requirements related to this. - Male participants are eligible to participate if they agree to follow applicable protocol requirements related to contraception.
• 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.

Exclusion Criteria

• History or presence of other concomitant chronic liver disease including: i) ImmunoglobulinG 4 (IgG4) related sclerosing cholangitis, or IgG4 ≥4x ULN at SV1. ii) Small duct PSC. iii) Documented history of secondary sclerosing cholangitis. iv) Presence of hepatitis B surface antigen (HBsAg) at screening. v) Hepatitis C virus (HCV) infection vi) Primary biliary cholangitis (PBC) or positive anti-mitochondrial antibody. vii) Alcohol-related liver disease. viii) Autoimmune hepatitis (AIH): Simplified Diagnostic Criteria of the IAIHG ≥6. ix) Presence of history of PSC-PBC or PSC-AIH overlap syndrome. x) Non-alcoholic steatohepatitis (NASH). SMD form protocol master data--23- INT / Version 1 Known history of alpha-1 antitrypsin deficiency
• Presence of percutaneous drain or bile duct stent at screening or within three months prior to screening.
• History of bacterial cholangitis within 60 days prior to the screening period, or participant on antibiotics for prophylaxis of recurrent cholangitis.
• History or any current suspicion of cholangiocarcinoma or elevated value of carbohydrate antigen 19-9 (CA19-9) >129 U/mL at SV1.
• Alpha-fetoprotein (AFP) >20 ng/mL with 4-phase liver computerised tomography (CT) or magnetic resonance imaging (MRI) suggesting presence of liver cancer.
• Participants with cirrhosis who are also classified as Child-Pugh B or C based on the Child-Pugh score. Participants with cirrhosis with Child-Pugh A score are allowed.
• History of clinically significant hepatic decompensation as described in the study protocol
• Presence or history of hepatocellular carcinoma.
• Medical conditions that may cause non-hepatic increases in ALP (e.g. Paget's disease).
• Medical conditions that may diminish life expectancy to <2 years, including known cancers.
• Participant has a positive test for human immunodeficiency virus (HIV) type 1 or 2 at SV1, or participant is known to have tested positive for HIV.
• Evidence of any other unstable or untreated clinically significant immunological, endocrine, neurological, gastrointestinal, haematologic, psychiatric diseases as evaluated by the investigator; other clinically significant conditions that are not well controlled
• Known malignancy or history of malignancy within the last 5 years, with the exception of local, successfully treated basal cell carcinoma or in-situ carcinoma of the uterine cervix.
• Participants with previous exposure to elafibranor
• ALT and/or AST >5x ULN
• Albumin <3.0 g/dL at SV1.
• Platelet count <100,000/microliter.
• International normalised ratio (INR) >1.3 due to altered hepatic function.
• Creatine phosphokinase (CPK) >2x ULN during screening period.
• Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ipsen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ipsen Medical, Director

Role: STUDY_DIRECTOR

Ipsen

Locations

Om Research LLC

Lancaster, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

University of California, Davis

Sacramento, California, United States

Sutter Health Van Ness Campus Medical Office Building

San Francisco, California, United States

Peak Gastroenterology Associates

Colorado Springs, Colorado, United States

South Denver Gastroenterology,P.C.

Englewood, Colorado, United States

Rocky Mountain Gastroenterology (RMG)

Littleton, Colorado, United States

Yale University School Of Medicine - Yale Center For Clinical Investigation

New Haven, Connecticut, United States

Schiff Center for Liver Diseases - University of Miami

Miami, Florida, United States

Covenant Research

Sarasota, Florida, United States

Piedmont Hospital - Piedmont Transplant Institute

Atlanta, Georgia, United States

Tandem Clinical Research GI

Marrero, Louisiana, United States

Mercy Medical Center

Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center, Liver Research Center

Boston, Massachusetts, United States

Huron Gastroenterology Associates - Center for Digestive Care

Ypsilanti, Michigan, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Southwest Gastroenterology Associates, PC (SWGA)

Albuquerque, New Mexico, United States

New York University Langone Health

New York, New York, United States

Gastro Health Research

Cincinnati, Ohio, United States

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Gastro One

Cordova, Tennessee, United States

University Of Texas Southwestern Medical Center At Dallas

Dallas, Texas, United States

American Research Corporation at The Texas Liver Institute

San Antonio, Texas, United States

Intermountain Medical Center

Murray, Utah, United States

University of Virginia Medical Center

Charlottesville, Virginia, United States

Bon Secours Richmond Community Hospital LLC. d/b/a Bon Secours Liver Institute of Richmond

Richmond, Virginia, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Liver Institute Northwest

Seattle, Washington, United States

University of Calgary

Calgary, Alberta, Canada

University Of Alberta Hospital-Zeidler Ledcor Centre

Edmonton, Alberta, Canada

Brampton Civic Hospital (BCH) - Osler Hepatitis Centre

Brampton, Ontario, Canada

Aspen Woods Clinic

Calgary, , Canada

Centre de Recherche du Centre Hospitalier de l'Universite de Montreal

Montreal, , Canada

G.I Research Institute

Vancouver, , Canada

Charite Campus Virchow

Berlin, , Germany

Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt

Frankfurt, , Germany

Universitaetsklinikum Heidelberg - Nationales Centrum fuer Tumorerkrankungen

Heidelberg, , Germany

University Hospital Ulm

Ulm, , Germany

Azienda Ospedaliero Universitaria Modena

Modena, , Italy

Azienda Ospedaliera di Padova - U.O.C. di Gastroenterologia

Padua, , Italy

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, , Italy

Gruppo Humanitas - Humanitas Research Hospital, Istituto Clinico Humanitas

Rozzano, , Italy

Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

Centro Hospitalar do Alto Ave - Hospital Senhora da Oliveira

Guimarães, , Portugal

Centro Hospitalar Universitario Lisboa Norte

Lisbon, , Portugal

Centro Hospitalar de Lisboa ocidental (CHLO), Hospital Egas Moniz

Lisbon, , Portugal

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Hospital General Universitario Gregorio Maranon (HGUGM)

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Puerta de Hierro

Majadahonda, , Spain

Hospital De Montecelo

Pontevedra, , Spain

Hospital Universitario Rio Hortega

Valladolid, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Aberdeen Royal Infirmary NHS Grampian Grampian Health Board

Aberdeen, , United Kingdom

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Frimley Park Hospital - Frimley Health NHS Foundation Trust

Frimley, , United Kingdom

Glasgow Royal Infirmary - Greater Glasgow Health Board

Glasgow, , United Kingdom

Hull Royal Infirmary - Hull University Teaching Hospitals NHS Trust

Hull, , United Kingdom

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

London, , United Kingdom

The Royal Free Hospital - Royal Free London NHS Foundation Trust

London, , United Kingdom

Countries

United States; Canada; Germany; Italy; Portugal; Spain; United Kingdom

References

Levy C, Abouda GF, Bilir BM, Bonder A, Bowlus CL, Campos-Varela I, Cazzagon N, Chandok N, Cheent K, Cortez-Pinto H, Demir M, Dill MT, Eksteen B, Fenkel JM, Gilroy R, Ko HH, Jacobson IM, Kallis Y, Kugelmas M, Luketic V, Mangia A, Montano-Loza AJ, Mukhopadhya A, Olveira A, Patel BC, Pietrangelo A, Pradhan F, Salcedo M, Shiffman ML, Sprinzl K, Swann R, Thorburn D, Thuluvath PJ, Trivedi PJ, Turnes J, Zein CO, Gomes da Silva H, Jaitly S, Miller B, Milligan C, Tavenard A, Kowdley KV. Safety and efficacy of elafibranor in primary sclerosing cholangitis: The ELMWOOD phase II randomized-controlled trial. J Hepatol. 2025 May 8:S0168-8278(25)00252-1. doi: 10.1016/j.jhep.2025.04.025. Online ahead of print.

Reference Type: DERIVED

PMID: 40350321 (View on PubMed)

Other Identifiers

2022-002695-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLIN-60190-453

Identifier Type: -

Identifier Source: org_study_id