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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05627362
Other study ID # CLIN-60190-453
Secondary ID 2022-002695-37
Status Recruiting
Phase Phase 2
First received
Last updated
Start date January 27, 2023
Est. completion date December 16, 2024

Study information

Verified date May 2024
Source Ipsen
Contact Ipsen Clinical Study Enquiries
Phone see email
Email clinical.trials@ipsen.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 60
Est. completion date December 16, 2024
Est. primary completion date December 16, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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 Design


Intervention

Drug:
Elafibranor 80 mg
Oral Tablet
Elafibranor 120 mg
Oral Tablet
Placebo Matched to Elafibranor 80 mg
Oral Tablet
Placebo Matched to Elafibranor 120 mg
Oral Tablet

Locations

Country Name City State
Canada Brampton Civic Hospital (BCH) - Osler Hepatitis Centre Brampton Ontario
Canada Aspen Woods Clinic Calgary
Canada University of Calgary Calgary Alberta
Canada University Of Alberta Hospital-Zeidler Ledcor Centre Edmonton Alberta
Canada Centre de Recherche du Centre Hospitalier de l'Universite de Montreal Montréal
Canada G.I Research Institute Vancouver
Germany 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
Italy Azienda Ospedaliero Universitaria Modena Modena
Italy Azienda Ospedaliera di Padova - U.O.C. di Gastroenterologia Padova
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
Portugal Centro Hospitalar do Alto Ave - Hospital Senhora da Oliveira Guimarães
Portugal Centro Hospitalar de Lisboa ocidental (CHLO), Hospital Egas Moniz Lisboa
Portugal Centro Hospitalar Universitario Lisboa Norte Lisboa
Spain 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
United Kingdom 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 States Southwest Gastroenterology Associates, PC (SWGA) Albuquerque New Mexico
United States Piedmont Hospital - Piedmont Transplant Institute Atlanta Georgia
United States Mercy Medical Center Baltimore Maryland
United States Beth Israel Deaconess Medical Center, Liver Research Center Boston Massachusetts
United States Medical University of South Carolina Charleston South Carolina
United States University of Virginia Medical Center Charlottesville Virginia
United States Gastro Health Research Cincinnati Ohio
United States Peak Gastroenterology Associates Colorado Springs Colorado
United States Gastro One Cordova Tennessee
United States University Of Texas Southwestern Medical Center At Dallas Dallas Texas
United States South Denver Gastroenterology,P.C. Englewood Colorado
United States Penn State Milton S Hershey Medical Center Hershey Pennsylvania
United States Om Research LLC Lancaster California
United States Rocky Mountain Gastroenterology (RMG) Littleton Colorado
United States Cedars-Sinai Medical Center Los Angeles California
United States Tandem Clinical Research GI Marrero Louisiana
United States Schiff Center for Liver Diseases - University of Miami Miami Florida
United States Intermountain Medical Center Murray Utah
United States Yale University School Of Medicine - Yale Center For Clinical Investigation New Haven Connecticut
United States New York University Langone Health New York New York
United States University of Nebraska Medical Center Omaha Nebraska
United States Thomas Jefferson University Philadelphia Pennsylvania
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 University of California, Davis Sacramento California
United States American Research Corporation at The Texas Liver Institute San Antonio Texas
United States Sutter Health Van Ness Campus Medical Office Building San Francisco California
United States Covenant Research Sarasota Florida
United States Liver Institute Northwest Seattle Washington
United States Huron Gastroenterology Associates - Center for Digestive Care Ypsilanti Michigan

Sponsors (1)

Lead Sponsor Collaborator
Ipsen

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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 Relative Change From Baseline in Alkaline Phosphate Levels (ALP) Double Blind Period: Baseline, Week 12, OLE Period: Baseline, Week 52, Week 96
Secondary Percentage of Participants With =40% Decrease from Baseline in ALP Levels Double Blind Period: Baseline, Week 12, OLE Period: Baseline, Week 52, Week 96
Secondary Absolute Change from Baseline in ALP Double Blind Period: Baseline, Week 12, OLE Period: Baseline, Week 52, Week 96
Secondary Percentage of Participants With ALP: <1.3x Upper Limit of Normal (ULN) and <1.5x ULN Double Blind Period: Week 12
Secondary Percentage of Participants who Normalised ALP Double Blind Period: Week 12
Secondary 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
Secondary Change From Baseline in Total bilirubin, Conjugated bilirubin Levels at Week 12 Baseline, Week 12
Secondary Change From Baseline in Albumin Levels at Week 12 Baseline, Week 12
Secondary Change from Baseline in Enhanced Liver Fibrosis (ELF) Test Score Double Blind Period: Baseline, Week 12
Secondary Change From Baseline in Liver Stiffness Measurement (LSM) Values Assessed by FibroScan® at Week 12 Double Blind Period: Baseline, Week 12
Secondary Change From Baseline in Other Non-invasive Hepatic Fibrosis Serum Markers as Measured by PAI-1, TGF-ß, Marker of type V Collagen Formation (Pro-C5), and Marker of Type III Collagen Formation (Pro-C3) Double Blind Period: Baseline, Week 12
Secondary Change From Baseline in Fibrosis-4 (FIB-4) and AST to Platelet Ratio Index (APRI) Double Blind Period: Baseline, Week 12
Secondary Change From Baseline in Cytokeratin-18 (CK-18) (M65 and M30) Levels Double Blind Period: Baseline, Week 12
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
See also
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