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

NCT05627362 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: CLIN-60190-4532022-002695-37
• Study Type: interventional
• Target: 68
• Locations: 7 countries
• Sites: 62

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

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants With Treatment Emergent Adverse Event (TEAEs), Treatment Related TEAEs, Serious Adverse (SAEs) and Adverse Events of Special Interest (AESIs)

  An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered 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.

  Double Blind Period: Baseline up to week 12, Open Label Extension (OLE) Period: Baseline up to week 100

• Percentage of Participants With Clinically Significant Changes in Physical Examination Findings

  Percentage of participants with clinically significant changes in physical examination findings will be reported. The clinical significance will be decided by the investigator.

  Double Blind Period: Baseline up to week 12, OLE Period: Baseline up to week 100

• Percentage of Participants With Clinically Significant changes in Laboratory Parameters (blood chemistry, hematology and coagulation)

  Percentage of participants with clinically significant change in laboratory parameters (blood chemistry, hematology and coagulation) will be reported. The clinical significance will be decided by the investigator.

  Double Blind Period: Baseline up to week 12, OLE Period: Baseline up to week 100

• Percentage 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 decided by the investigator.

  Double Blind Period: Baseline up to week 12, OLE Period: Baseline up to week 100

• Percentage of Participants With 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 decided by the investigator.

  Double Blind Period: Baseline up to week 12, OLE Period: Baseline up to week 100

Secondary Outcomes (18)

• Relative Change From Baseline in Alkaline Phosphate Levels (ALP)

  Double Blind Period: Baseline, Week 12, OLE Period: Baseline, Week 52, Week 96

• Percentage of Participants With ≥40% Decrease from Baseline in ALP Levels

  Double Blind Period: Baseline, Week 12, OLE Period: Baseline, Week 52, Week 96

• Absolute Change from Baseline in ALP

  Double Blind Period: Baseline, Week 12, OLE Period: Baseline, Week 52, Week 96

• Percentage of Participants With ALP: <1.3x Upper Limit of Normal (ULN) and <1.5x ULN

  Double Blind Period: Week 12

• Percentage of Participants who Normalised ALP

  Double Blind Period: Week 12

Study Arms (4)

Double-Blind Period: Elafibranor 80 mg

EXPERIMENTAL

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.

Drug: Elafibranor 80 mg; Drug: Placebo Matched to Elafibranor 120 mg

Double-Blind Period: Elafibranor 120 mg

EXPERIMENTAL

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.

Drug: Elafibranor 120 mg; Drug: Placebo Matched to Elafibranor 80 mg

Double-Blind Period: Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo Matched to Elafibranor 80 mg

Open-Label Extension Period: Elafibranor 120 mg

EXPERIMENTAL

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

Drug: Elafibranor 120 mg

Interventions

Placebo Matched to Elafibranor 80 mg DRUG

Oral Tablet

Double-Blind Period: Elafibranor 120 mg; Double-Blind Period: Placebo

Placebo Matched to Elafibranor 120 mg DRUG

Oral Tablet

Double-Blind Period: Elafibranor 80 mg

Elafibranor 80 mg DRUG

Oral Tablet

Also known as: GFT505

Double-Blind Period: Elafibranor 80 mg

Elafibranor 120 mg DRUG

Oral Tablet

Also known as: GFT505

Double-Blind Period: Elafibranor 120 mg; Open-Label Extension Period: Elafibranor 120 mg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ipsen: lead

Study Sites (62)

Om Research LLC

Lancaster, California, 93534, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California, Davis

Sacramento, California, 95817, United States

Location

Sutter Health Van Ness Campus Medical Office Building

San Francisco, California, 94109, United States

Location

Peak Gastroenterology Associates

Colorado Springs, Colorado, 80907, United States

Location

South Denver Gastroenterology,P.C.

Englewood, Colorado, 80113, United States

Location

Rocky Mountain Gastroenterology (RMG)

Littleton, Colorado, 80120, United States

Location

Yale University School Of Medicine - Yale Center For Clinical Investigation

New Haven, Connecticut, 06510, United States

Location

Schiff Center for Liver Diseases - University of Miami

Miami, Florida, 33136, United States

Location

Covenant Research

Sarasota, Florida, 34240, United States

Location

Piedmont Hospital - Piedmont Transplant Institute

Atlanta, Georgia, 30309, United States

Location

Tandem Clinical Research GI

Marrero, Louisiana, 70072, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Beth Israel Deaconess Medical Center, Liver Research Center

Boston, Massachusetts, 02215, United States

Location

Huron Gastroenterology Associates - Center for Digestive Care

Ypsilanti, Michigan, 48197, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Southwest Gastroenterology Associates, PC (SWGA)

Albuquerque, New Mexico, 87109-4342, United States

Location

New York University Langone Health

New York, New York, 06510, United States

Location

Gastro Health Research

Cincinnati, Ohio, 45219, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19017, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Gastro One

Cordova, Tennessee, 38018, United States

Location

University Of Texas Southwestern Medical Center At Dallas

Dallas, Texas, 75235, United States

Location

American Research Corporation at The Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

University of Virginia Medical Center

Charlottesville, Virginia, 22093, United States

Location

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

Richmond, Virginia, 23226, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Liver Institute Northwest

Seattle, Washington, 98105, United States

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

University Of Alberta Hospital-Zeidler Ledcor Centre

Edmonton, Alberta, T6G 2X8, Canada

Location

Brampton Civic Hospital (BCH) - Osler Hepatitis Centre

Brampton, Ontario, L6R 3J7, Canada

Location

Aspen Woods Clinic

Calgary, T3H 0V5, Canada

Location

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

Montreal, H2X 0A9, Canada

Location

G.I Research Institute

Vancouver, V6Z 2K5, Canada

Location

Charite Campus Virchow

Berlin, 13353, Germany

Location

Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt

Frankfurt, 60590, Germany

Location

Universitaetsklinikum Heidelberg - Nationales Centrum fuer Tumorerkrankungen

Heidelberg, 69120, Germany

Location

University Hospital Ulm

Ulm, 89081, Germany

Location

Azienda Ospedaliero Universitaria Modena

Modena, 41124, Italy

Location

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

Padova, 35128, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, 90127, Italy

Location

Gruppo Humanitas - Humanitas Research Hospital, Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, 71013, Italy

Location

Centro Hospitalar do Alto Ave - Hospital Senhora da Oliveira

Guimarães, 4800-055, Portugal

Location

Centro Hospitalar Universitario Lisboa Norte

Lisbon, 1345-035, Portugal

Location

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

Lisbon, 1349-019, Portugal

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Maranon (HGUGM)

Madrid, 28007, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, 28222, Spain

Location

Hospital De Montecelo

Pontevedra, 36071, Spain

Location

Hospital Universitario Rio Hortega

Valladolid, 47012, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Aberdeen Royal Infirmary NHS Grampian Grampian Health Board

Aberdeen, AB25 2ZD, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, B15 2TT, United Kingdom

Location

Frimley Park Hospital - Frimley Health NHS Foundation Trust

Frimley, GU16 7UJ, United Kingdom

Location

Glasgow Royal Infirmary - Greater Glasgow Health Board

Glasgow, G4 0SF, United Kingdom

Location

Hull Royal Infirmary - Hull University Teaching Hospitals NHS Trust

Hull, HU3 2JZ, United Kingdom

Location

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

London, E1 1BB, United Kingdom

Location

The Royal Free Hospital - Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Related Publications (1)

• 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. 2026 Jan;84(1):74-85. doi: 10.1016/j.jhep.2025.04.025. Epub 2025 May 10.

  PMID: 40350321 DERIVED

MeSH Terms

Conditions

Cholangitis, Sclerosing

Interventions

2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Study Officials

• Ipsen Medical, Director

  Ipsen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2022
• First Posted: November 25, 2022
• Study Start: December 29, 2022
• Primary Completion (Estimated): August 28, 2026
• Study Completion (Estimated): August 28, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and/or EU.
• Access Criteria: Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).

Locations

PT (3); ES (7); CA (6); IT (5); US (30); DE (4); GB (7)