A Study to Assess Safety and Effectiveness of Elafibranor in Adult Participants With Primary Sclerosing Cholangitis. (ELMWOOD)
Primary Sclerosing Cholangitis
About this trial
This is an interventional treatment trial for Primary Sclerosing Cholangitis
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
Sites / Locations
- Om Research LLCRecruiting
- Cedars-Sinai Medical Center
- University of California, Davis
- Sutter Health Van Ness Campus Medical Office Building
- Peak Gastroenterology AssociatesRecruiting
- South Denver Gastroenterology,P.C.Recruiting
- Rocky Mountain Gastroenterology (RMG)Recruiting
- Yale University School Of Medicine - Yale Center For Clinical InvestigationRecruiting
- Schiff Center for Liver Diseases - University of MiamiRecruiting
- Covenant ResearchRecruiting
- Piedmont Hospital - Piedmont Transplant InstituteRecruiting
- Tandem Clinical Research GIRecruiting
- Mercy Medical CenterRecruiting
- Beth Israel Deaconess Medical Center, Liver Research Center
- Huron Gastroenterology Associates - Center for Digestive Care
- University of Nebraska Medical CenterRecruiting
- Southwest Gastroenterology Associates, PC (SWGA)Recruiting
- New York University Langone HealthRecruiting
- Gastro Health ResearchRecruiting
- Penn State Milton S Hershey Medical Center
- Thomas Jefferson University
- Medical University of South CarolinaRecruiting
- Gastro OneRecruiting
- University Of Texas Southwestern Medical Center At Dallas
- American Research Corporation at The Texas Liver InstituteRecruiting
- Intermountain Medical CenterRecruiting
- University of Virginia Medical Center
- Bon Secours Richmond Community Hospital LLC. d/b/a Bon Secours Liver Institute of Richmond
- Virginia Commonwealth UniversityRecruiting
- Liver Institute NorthwestRecruiting
- University of Calgary
- University Of Alberta Hospital-Zeidler Ledcor Centre
- Brampton Civic Hospital (BCH) - Osler Hepatitis Centre
- Aspen Woods ClinicRecruiting
- Centre de Recherche du Centre Hospitalier de l'Universite de MontrealRecruiting
- G.I Research InstituteRecruiting
- Charite Campus VirchowRecruiting
- Klinikum der Johann Wolfgang Goethe-Universitaet FrankfurtRecruiting
- Universitaetsklinikum Heidelberg - Nationales Centrum fuer Tumorerkrankungen
- University Hospital Ulm
- Azienda Ospedaliero Universitaria Modena
- Azienda Ospedaliera di Padova - U.O.C. di Gastroenterologia
- Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
- Gruppo Humanitas - Humanitas Research Hospital, Istituto Clinico HumanitasRecruiting
- Ospedale Casa Sollievo della Sofferenza
- Centro Hospitalar do Alto Ave - Hospital Senhora da Oliveira
- Centro Hospitalar Universitario Lisboa Norte
- Centro Hospitalar de Lisboa ocidental (CHLO), Hospital Egas Moniz
- Hospital Universitario Vall d'HebronRecruiting
- Hospital General Universitario Gregorio Maranon (HGUGM)
- Hospital Universitario La PazRecruiting
- Hospital Universitario Puerta de HierroRecruiting
- Hospital De MonteceloRecruiting
- Hospital Universitario Rio Hortega
- Hospital Universitario Miguel ServetRecruiting
- Aberdeen Royal Infirmary NHS Grampian Grampian Health Board
- Queen Elizabeth Hospital
- Frimley Park Hospital - Frimley Health NHS Foundation Trust
- Glasgow Royal Infirmary - Greater Glasgow Health Board
- Hull Royal Infirmary - Hull University Teaching Hospitals NHS Trust
- Ambrose King Centre-Royal London Hospital-Barts Health NHS Trust
- The Royal Free Hospital - Royal Free London NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Placebo Comparator
Experimental
Double-Blind Period: Elafibranor 80 mg
Double-Blind Period: Elafibranor 120 mg
Double-Blind Period: Placebo
Open-Label Extension Period: Elafibranor 120 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.
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.
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.
Participant will receive one tablet per day (elafibranor 120 mg) over the 96 weeks in Open-Label extension period.