Primary Sclerosing CholangitisPhase 2ELMWOODNCT05627362
A Study to Assess Safety and Effectiveness of Elafibranor in Adult Participants With Primary Sclerosing Cholangitis.
A Phase 2 study testing Elafibranor 80 mg and Elafibranor 120 mg in people with Primary Sclerosing Cholangitis, run by Ipsen at 62 sites in 7 countries.
Trial summary
This study will evaluate the effects of elafibranor (the study drug) in participants with Primary Sclerosing Cholangitis (PSC) during the double-blind period, an initial 96 week open-label extension (OLE) period, and an optional open-label extension long-term (OLE-LT) period beyond OLE Week 96. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary Sclerosing Cholangitis
- What is being tested?
- Elafibranor 80 mg and Elafibranor 120 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 62 sitesin 7 countries
- Study dates
- 29 Dec 2022to 23 Sep 2031
- Phase
- Phase 2
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The following inclusion criteria apply to entry into the double-blind period and initial open-label extension (OLE) period up to OLE Week 96, unless otherwise specified.
- 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.
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- 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.
- Inclusion Criteria for Entry into Optional Open-Label Extension Long-Term (OLE-LT) Period Beyond Week 96
- For entry into the optional OLE-LT period, participants:
- Must have completed the initial OLE period up to OLE Week 96
- Must not have permanently discontinued the study intervention during the initial OLE period
- Must, in the opinion of the investigator, benefit from continuing to receive study intervention The eligibility criteria assessed at Screening Visit 1 (SV1) for entry into the double-blind period are not reassessed for entry into the optional OLE-LT period.
- Contraception requirements applicable during the OLE-LT period:
- Male participants: No contraception requirements apply.
- Female participants of childbearing potential: Must continue to use a highly effective contraceptive method during study intervention and for at least one month after the last dose. If using a hormonal contraceptive, an additional barrier method or a switch to a highly effective non-hormonal method is required.
Who cannot join
- 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.
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- 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
Trial locations and contacts
62 sites in 7 countries.
62 sites in 7 countries
United States30 sites
Southwest Gastroenterology Associates, PC (SWGA)
Albuquerque, New Mexico, 87109-4342
Piedmont Hospital - Piedmont Transplant Institute
Atlanta, Georgia, 30309
Mercy Medical Center
Baltimore, Maryland, 21202
Beth Israel Deaconess Medical Center, Liver Research Center
Boston, Massachusetts, 02215
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Virginia Medical Center
Charlottesville, Virginia, 22093
Gastro Health Research
Cincinnati, Ohio, 45219
Peak Gastroenterology Associates
Colorado Springs, Colorado, 80907
Gastro One
Cordova, Tennessee, 38018
University Of Texas Southwestern Medical Center At Dallas
Dallas, Texas, 75235
South Denver Gastroenterology,P.C.
Englewood, Colorado, 80113
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033
Om Research LLC
Lancaster, California, 93534
Rocky Mountain Gastroenterology (RMG)
Littleton, Colorado, 80120
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Tandem Clinical Research GI
Marrero, Louisiana, 70072
Schiff Center for Liver Diseases - University of Miami
Miami, Florida, 33136
Intermountain Medical Center
Murray, Utah, 84107
Yale University School Of Medicine - Yale Center For Clinical Investigation
New Haven, Connecticut, 06510
New York University Langone Health
New York, New York, 06510
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Thomas Jefferson University
Philadelphia, Pennsylvania, 19017
Bon Secours Richmond Community Hospital LLC. d/b/a Bon Secours Liver Institute of Richmond
Richmond, Virginia, 23226
Virginia Commonwealth University
Richmond, Virginia, 23298
University of California, Davis
Sacramento, California, 95817
American Research Corporation at The Texas Liver Institute
San Antonio, Texas, 78215
Sutter Health Van Ness Campus Medical Office Building
San Francisco, California, 94109
Covenant Research
Sarasota, Florida, 34240
Liver Institute Northwest
Seattle, Washington, 98105
Huron Gastroenterology Associates - Center for Digestive Care
Ypsilanti, Michigan, 48197
Spain7 sites
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Hospital General Universitario Gregorio Maranon (HGUGM)
Madrid, 28007
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Puerta de Hierro
Majadahonda, 28222
Hospital De Montecelo
Pontevedra, 36071
Hospital Universitario Rio Hortega
Valladolid, 47012
Hospital Universitario Miguel Servet
Zaragoza, 50009
United Kingdom7 sites
Aberdeen Royal Infirmary NHS Grampian Grampian Health Board
Aberdeen, AB25 2ZD
Queen Elizabeth Hospital
Birmingham, B15 2TT
Frimley Park Hospital - Frimley Health NHS Foundation Trust
Frimley, GU16 7UJ
Glasgow Royal Infirmary - Greater Glasgow Health Board
Glasgow, G4 0SF
Hull Royal Infirmary - Hull University Teaching Hospitals NHS Trust
Hull, HU3 2JZ
Ambrose King Centre-Royal London Hospital-Barts Health NHS Trust
London, E1 1BB
The Royal Free Hospital - Royal Free London NHS Foundation Trust
London, NW3 2QG
Canada6 sites
Brampton Civic Hospital (BCH) - Osler Hepatitis Centre
Brampton, Ontario, L6R 3J7
University of Calgary
Calgary, Alberta, T2N 4Z6
Aspen Woods Clinic
Calgary, T3H 0V5
University Of Alberta Hospital-Zeidler Ledcor Centre
Edmonton, Alberta, T6G 2X8
Centre de Recherche du Centre Hospitalier de l'Universite de Montreal
Montreal, H2X 0A9
G.I Research Institute
Vancouver, V6Z 2K5
Italy5 sites
Azienda Ospedaliero Universitaria Modena
Modena, 41124
Azienda Ospedaliera di Padova - U.O.C. di Gastroenterologia
Padova, 35128
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Palermo, 90127
Gruppo Humanitas - Humanitas Research Hospital, Istituto Clinico Humanitas
Rozzano, 20089
Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo, 71013
Germany4 sites
Charite Campus Virchow
Berlin, 13353
Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt
Frankfurt, 60590
Universitaetsklinikum Heidelberg - Nationales Centrum fuer Tumorerkrankungen
Heidelberg, 69120
University Hospital Ulm
Ulm, 89081
Portugal3 sites
Centro Hospitalar do Alto Ave - Hospital Senhora da Oliveira
Guimarães, 4800-055
Centro Hospitalar Universitario Lisboa Norte
Lisbon, 1345-035
Centro Hospitalar de Lisboa ocidental (CHLO), Hospital Egas Moniz
Lisbon, 1349-019
About this study
Official title: A Phase II, Multicenter, Double-Blind, Randomised, Placebo-Controlled Study and Open Label Long Term Extension to Evaluate the Safety and Efficacy of Elafibranor in Adult Participants With Primary Sclerosing Cholangitis (PSC).
This study will evaluate the effects of elafibranor (the study drug) in participants with Primary Sclerosing Cholangitis (PSC) during the double-blind period, an initial 96 week open-label extension (OLE) period, and an optional open-label extension long-term (OLE-LT) period beyond OLE Week 96. 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, including long-term safety during the open-label extension periods. 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
- Being tested
- Elafibranor 80 mg, Elafibranor 120 mg, Placebo Matched to Elafibranor 80 mg, Placebo Matched to Elafibranor 120 mg
- Medical subject headings
- Cholangitis, Sclerosing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Elafibranor 80 mgDrug
Also called GFT505
Oral Tablet
Elafibranor 120 mgDrug
Also called GFT505
Oral Tablet
Placebo Matched to Elafibranor 80 mgDrug
Oral Tablet
Placebo Matched to Elafibranor 120 mgDrug
Oral Tablet
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Placebo Matched to Elafibranor 80 mg |
| Initial Open-Label Extension (OLE) Period up to OLE Week 96: Elafibranor 120 mg | Experimental | Participant will receive one tablet per day (elafibranor 120 mg) during the initial 96-weeks Open-Label extension period. Receives: Drug: Elafibranor 120 mg |
| Open-Label Extension Long-Term (OLE-LT) Period Beyond OLE Week 96: Elafibranor 120 mg | Experimental | Participant will receive one tablet per day (elafibranor 120 mg) during the optional Open-Label Extension Long-Term period beyond OLE Week 96 Receives: Drug: Elafibranor 120 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Related TEAEs, Serious Adverse Events (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.
Measured: Double Blind Period: Baseline up to week 12, Initial Open Label Extension (OLE) Period: Baseline up to week 100, Open-Label Extension Long-Term (OLE-LT) Period Beyond OLE Week 96: OLE-LT baseline up to OLE-LT Week 260
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.
Measured: Double Blind Period: Baseline up to week 12, Initial 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.
Measured: Double Blind Period: Baseline up to week 12, Initial 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.
Measured: Double Blind Period: Baseline up to week 12, Initial 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.
Measured: Double Blind Period: Baseline up to week 12, Initial OLE Period: Baseline up to week 100
Secondary outcomes (21)
Relative Change From Baseline in Alkaline Phosphatase Levels (ALP)
Measured: Double Blind Period: Baseline, Week 12, Initial OLE Period: Baseline, Week 52, Week 96, OLE-LT Period Beyond OLE Week 96: OLE-LT baseline up to OLE-LT Week 260
Percentage of Participants With ≥40% Decrease from Baseline in ALP Levels
Measured: Double Blind Period: Baseline, Week 12, Initial OLE Period: Baseline, Week 52, Week 96
Absolute Change from Baseline in ALP
Measured: Double Blind Period: Baseline, Week 12, Initial OLE Period: Baseline, Week 52, Week 96
Percentage of Participants With ALP: <1.3x Upper Limit of Normal (ULN) and <1.5x ULN
Measured: Double Blind Period: Week 12
Percentage of Participants who Normalised ALP
Measured: Double Blind Period: Week 12
Change From Baseline in Alanine Transaminase (ALT), Aspartate Transaminase (AST), Gamma-glutamyl transferase (GGT) Levels
Measured: Baseline, Week 12, Initial OLE-LT Period Beyond OLE Week 96: OLE-LT baseline up to OLE-LT Week 260
Change From Baseline in 5' Nucleotidase and Fractionated ALP Levels at Week 12
Measured: Baseline, Week 12
Change From Baseline in Total bilirubin Levels
Measured: Baseline, Week 12, Initial OLE-LT Period Beyond OLE Week 96: OLE-LT baseline up to OLE-LT Week 260
Change From Baseline in Conjugated bilirubin Levels at Week 12
Measured: Baseline, Week 12
Change From Baseline in Albumin Levels at Week 12
Measured: Baseline, Week 12
Change from Baseline in Enhanced Liver Fibrosis (ELF) Test Score
Measured: Double Blind Period: Baseline, Week 12
Change From Baseline in Liver Stiffness Measurement (LSM) Values Assessed by FibroScan® at Week 12
Measured: Double Blind Period: Baseline, Week 12
Change From Baseline in Other Non-invasive Hepatic Fibrosis Serum Markers as Measured by PAI-1, TGF-β, Marker of type V Collagen Formation (Pro-C5), and Marker of Type III Collagen Formation (Pro-C3)
Measured: Double Blind Period: Baseline, Week 12
Change From Baseline in Fibrosis-4 (FIB-4) and AST to Platelet Ratio Index (APRI)
Measured: Double Blind Period: Baseline, Week 12
Change From Baseline in Cytokeratin-18 (CK-18) (M65 and M30) Levels
Measured: Double Blind Period: Baseline, Week 12
Pharmacokinetics (PK) of Elafibranor and its Metabolite GFT1007: Area Under the Concentration-time Curve Over the Dosing Interval from Time 0 to 24 hours(AUC0-24)
AUC 0-24 will be recorded from the PK blood samples collected.
Measured: Pre-dose, 0.5 hour (h), 1h, between 1.5 hours and 2h, 4h, and 6h after dosing at Week 4
PK of Elafibranor and its Metabolite GFT1007: Maximum (peak) Observed Plasma Drug Concentration (Cmax)
Measured: Pre-dose, 0.5 hour (h), 1h, between 1.5h and 2h, 4h, and 6h after dosing at Week 4
PK of Elafibranor and its Metabolite GFT1007: Time to Maximum Observed Drug Concentration (Tmax)
Tmax will be recorded from the PK blood samples collected.
Measured: Pre-dose, 0.5 hour (h), 1h, between 1.5h and 2h, 4h, and 6h after dosing at Week 4
PK of Elafibranor and its Metabolite GFT1007: Total Body Clearance (Cl/F)
Cl/F will be recorded from the PK blood samples collected.
Measured: Double Blind Period: Baseline up to Week 12
PK of Elafibranor and its Metabolite GFT1007: Volume of distribution (Vz)
Vz will be recorded from the PK blood samples collected.
Measured: Double Blind Period: Baseline up to Week 12
Number and Percentage of Participants With Clinical Outcome Events During the OLE-LT Period
Measured: Initial OLE-LT Period Beyond OLE Week 96: OLE-LT baseline up to OLE-LT Week 260
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2022
- Study start29 Dec 2022
- Primary completion23 Sep 2031 (estimated)
- Study completion23 Sep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Sclerosing CholangitisStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 68 participants (actual)
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
- NCT05627362
- Sponsor's protocol ID
- CLIN-60190-453
- Other IDs
- 2022-002695-37, 2024-511370-72-00
- Acronym
- ELMWOOD
- Status last verified
- Oct 2026
- First submitted
- 22 Nov 2022
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- 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.
Publications
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.
PubMed 40350321