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

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). 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.

Study Overview

• Status: Recruiting
• Conditions: Primary Sclerosing Cholangitis
• Intervention / Treatment: Drug: Elafibranor 80 mg; Drug: Placebo Matched to Elafibranor 120 mg; Drug: Elafibranor 120 mg; Drug: Placebo Matched to Elafibranor 80 mg

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ipsen Clinical Study Enquiries; Phone Number: see email; Email: clinical.trials@ipsen.com

Study Locations

• Canada
  • Calgary, Canada, T3H 0V5
    • Recruiting
    • Aspen Woods Clinic
  • Montréal, Canada, H2X 0A9
    • Recruiting
    • Centre de Recherche du Centre Hospitalier de l'Université de Montréal
    • Contact: Genge Partners
  • Vancouver, Canada, V6Z 2K5
    • Recruiting
    • G.I Research Institute
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Not yet recruiting
      • University of Calgary
    • Edmonton, Alberta, Canada, T6G 2X8
      • Recruiting
      • University Of Alberta Hospital-Zeidler Ledcor Centre
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • Not yet recruiting
      • Brampton Civic Hospital (BCH) - Osler Hepatitis Centre
• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charite Campus Virchow
    • Contact: Praxis U Köpenick
  • Frankfurt, Germany, 60590
    • Recruiting
    • Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitaetsklinikum Heidelberg - Nationales Centrum fuer Tumorerkrankungen
  • Ulm, Germany, 89081
    • Recruiting
    • University Hospital Ulm
• Italy
  • Modena, Italy, 41124
    • Not yet recruiting
    • Azienda Ospedaliero Universitaria Modena
  • Padova, Italy, 35128
    • Not yet recruiting
    • Azienda Ospedaliera di Padova - U.O.C. di Gastroenterologia
  • Palermo, Italy, 90127
    • Recruiting
    • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
  • Rozzano, Italy, 20089
    • Recruiting
    • Gruppo Humanitas - Humanitas Research Hospital, Istituto Clinico Humanitas
    • Contact: IRCCS IC Humanitas
  • San Giovanni Rotondo, Italy, 71013
    • Not yet recruiting
    • Ospedale Casa Sollievo della Sofferenza
• Portugal
  • Guimarães, Portugal, 4800-055
    • Recruiting
    • Centro Hospitalar do Alto Ave - Hospital Senhora da Oliveira
  • Lisboa, Portugal, 1345-035
    • Recruiting
    • Centro Hospitalar Universitário Lisboa Norte
    • Contact: Centro H de Lisboa ocidental (CHLO), Hospital Egas Moniz
  • Lisboa, Portugal, 1349-019
    • Recruiting
    • Centro Hospitalar de Lisboa ocidental (CHLO), Hospital Egas Moniz
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall d'Hebrón
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Not yet recruiting
    • Hospital General Universitario Gregorio Maranon (HGUGM)
  • Majadahonda, Spain, 28222
    • Recruiting
    • Hospital Universitario Puerta De Hierro
  • Pontevedra, Spain, 36071
    • Recruiting
    • Hospital de Montecelo
  • Valladolid, Spain, 47012
    • Recruiting
    • Hospital Universitario Rio Hortega
  • Zaragoza, Spain, 50009
    • Recruiting
    • Hospital Universitario Miguel Servet
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZD
    • Recruiting
    • Aberdeen Royal Infirmary NHS Grampian Grampian Health Board
  • Birmingham, United Kingdom, B15 2TT
    • Not yet recruiting
    • Queen Elizabeth Hospital
  • Frimley, United Kingdom, GU16 7UJ
    • Recruiting
    • Frimley Park Hospital - Frimley Health NHS Foundation Trust
  • Glasgow, United Kingdom, G4 0SF
    • Recruiting
    • Glasgow Royal Infirmary - Greater Glasgow Health Board
  • Hull, United Kingdom, HU3 2JZ
    • Recruiting
    • Hull Royal Infirmary - Hull University Teaching Hospitals NHS Trust
  • London, United Kingdom, NW3 2QG
    • Not yet recruiting
    • The Royal Free Hospital - Royal Free London NHS Foundation Trust
  • London, United Kingdom, E1 1BB
    • Recruiting
    • Ambrose King Centre-Royal London Hospital-Barts Health NHS Trust
• United States
  • California
    • Lancaster, California, United States, 93534
      • Recruiting
      • OM Research LLC
    • Los Angeles, California, United States, 90048
      • Not yet recruiting
      • Cedars-Sinai Medical Center
    • Sacramento, California, United States, 95817
      • Recruiting
      • University of California, Davis
    • San Francisco, California, United States, 94109
      • Not yet recruiting
      • Sutter Health Van Ness Campus Medical Office Building
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Recruiting
      • Peak Gastroenterology Associates
    • Englewood, Colorado, United States, 80113
      • Recruiting
      • South Denver Gastroenterology,P.C.
    • Littleton, Colorado, United States, 80120
      • Recruiting
      • Rocky Mountain Gastroenterology (RMG)
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale University School Of Medicine - Yale Center For Clinical Investigation
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • Schiff Center for Liver Diseases - University of Miami
    • Sarasota, Florida, United States, 34240
      • Recruiting
      • Covenant Research
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Recruiting
      • Piedmont Hospital - Piedmont Transplant Institute
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Recruiting
      • Tandem Clinical Research GI
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Recruiting
      • Mercy Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center, Liver Research Center
  • Michigan
    • Ypsilanti, Michigan, United States, 48197
      • Not yet recruiting
      • Huron Gastroenterology Associates - Center for Digestive Care
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University of Nebraska Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109-4342
      • Recruiting
      • Southwest Gastroenterology Associates, PC (SWGA)
  • New York
    • New York, New York, United States, 06510
      • Recruiting
      • New York University Langone Health
      • Contact: Yale USOMYCFC Investigation
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • Gastro Health Research
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Penn State Milton S Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19017
      • Recruiting
      • Thomas Jefferson University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Recruiting
      • Gastro One
  • Texas
    • Dallas, Texas, United States, 75235
      • Not yet recruiting
      • University of Texas Southwestern Medical Center at Dallas
    • San Antonio, Texas, United States, 78215
      • Recruiting
      • American Research Corporation at the Texas Liver Institute
  • Utah
    • Murray, Utah, United States, 84107
      • Recruiting
      • Intermountain Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22093
      • Not yet recruiting
      • University of Virginia Medical Center
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23226
      • Recruiting
      • Bon Secours Richmond Community Hospital LLC. d/b/a Bon Secours Liver Institute of Richmond
      • Contact: Virginia C University
  • Washington
    • Seattle, Washington, United States, 98105
      • Recruiting
      • Liver Institute Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria :

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Elafibranor 80 mg; Oral Tablet; Other Names: GFT505; Drug: Placebo Matched to Elafibranor 120 mg; Oral Tablet
Experimental: 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.	Drug: Elafibranor 120 mg; Oral Tablet; Other Names: GFT505; Drug: Placebo Matched to Elafibranor 80 mg; Oral Tablet
Placebo Comparator: 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.	Drug: Placebo Matched to Elafibranor 80 mg; Oral Tablet
Experimental: 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.	Drug: Elafibranor 120 mg; Oral Tablet; Other Names: GFT505

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Change From Baseline in Alanine Transaminase (ALT),Aspartate Transaminase (AST), Gamma-glutamyl transferase (GGT), 5' Nucleotidase and Fractionated ALP Levels at Week 12		Baseline, Week 12
Change From Baseline in Total bilirubin, Conjugated bilirubin Levels at Week 12		Baseline, Week 12
Change From Baseline in Albumin Levels at Week 12		Baseline, Week 12
Change from Baseline in Enhanced Liver Fibrosis (ELF) Test Score		Double Blind Period: Baseline, Week 12
Change From Baseline in Liver Stiffness Measurement (LSM) Values Assessed by FibroScan® at Week 12		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)		Double Blind Period: Baseline, Week 12
Change From Baseline in Fibrosis-4 (FIB-4) and AST to Platelet Ratio Index (APRI)		Double Blind Period: Baseline, Week 12
Change From Baseline in Cytokeratin-18 (CK-18) (M65 and M30) Levels		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.	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)		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.	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.	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.	Double Blind Period: Baseline up to Week 12

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2023
• Primary Completion (Estimated): December 16, 2024
• Study Completion (Estimated): December 16, 2024

Study Registration Dates

• First Submitted: November 22, 2022
• First Submitted That Met QC Criteria: November 23, 2022
• First Posted (Actual): November 25, 2022

Study Record Updates

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

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing
• Other Study ID Numbers: CLIN-60190-453; 2022-002695-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.

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

• IPD Sharing Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• IPD Sharing Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

Drug and device information, study documents

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