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

Primary Sclerosing Cholangitis Clinical Trial

— ELMWOOD  

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).

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
• Start date: January 27, 2023
• Est. completion date: December 16, 2024

Study information

• Verified date: March 2024
• Source: Ipsen
• Contact: Ipsen Clinical Study Enquiries
• Phone: see email
• Email: clinical.trials[@]ipsen.com
• Is FDA regulated: No
• 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

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

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