Clinical trial NCT05627362: A Study to Assess Safety and Effectiveness of Elafibranor in Adult Participants With Primary Sclerosing Cholangitis.
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).
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Primary Sclerosing Cholangitis
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2022-11-25
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


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

Primary outcomes:
measure: Percentage of Participants With Treatment Emergent Adverse Event (TEAEs), Treatment Related TEAEs, Serious Adverse (SAEs) and Adverse Events of Special Interest (AESIs)
timeFrame: Double Blind Period: Baseline up to week 12, Open Label Extension (OLE) Period: Baseline up to week 100
measure: Percentage of Participants With Clinically Significant Changes in Physical Examination Findings
timeFrame: Double Blind Period: Baseline up to week 12, OLE Period: Baseline up to week 100
measure: Percentage of Participants With Clinically Significant changes in Laboratory Parameters (blood chemistry, hematology and coagulation)
timeFrame: Double Blind Period: Baseline up to week 12, OLE Period: Baseline up to week 100
measure: Percentage of Participants With Clinically Significant Changes in Vital Signs
timeFrame: Double Blind Period: Baseline up to week 12, OLE Period: Baseline up to week 100
measure: Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Readings
timeFrame: Double Blind Period: Baseline up to week 12, OLE Period: Baseline up to week 100
Secondary outcomes:
measure: Relative Change From Baseline in Alkaline Phosphate Levels (ALP)
timeFrame: Double Blind Period: Baseline, Week 12, OLE Period: Baseline, Week 52, Week 96
measure: Percentage of Participants With ≥40% Decrease from Baseline in ALP Levels
timeFrame: Double Blind Period: Baseline, Week 12, OLE Period: Baseline, Week 52, Week 96
measure: Absolute Change from Baseline in ALP
timeFrame: Double Blind Period: Baseline, Week 12, OLE Period: Baseline, Week 52, Week 96
measure: Percentage of Participants With ALP: <1.3x Upper Limit of Normal (ULN) and <1.5x ULN
timeFrame: Double Blind Period: Week 12
measure: Percentage of Participants who Normalised ALP
timeFrame: Double Blind Period: Week 12
measure: Change From Baseline in Alanine Transaminase (ALT),Aspartate Transaminase (AST), Gamma-glutamyl transferase (GGT), 5' Nucleotidase and Fractionated ALP Levels at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Total bilirubin, Conjugated bilirubin Levels at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Albumin Levels at Week 12
timeFrame: Baseline, Week 12
measure: Change from Baseline in Enhanced Liver Fibrosis (ELF) Test Score
timeFrame: Double Blind Period: Baseline, Week 12
measure: Change From Baseline in Liver Stiffness Measurement (LSM) Values Assessed by FibroScan® at Week 12
timeFrame: Double Blind Period: Baseline, Week 12
measure: 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)
timeFrame: Double Blind Period: Baseline, Week 12
measure: Change From Baseline in Fibrosis-4 (FIB-4) and AST to Platelet Ratio Index (APRI)
timeFrame: Double Blind Period: Baseline, Week 12
measure: Change From Baseline in Cytokeratin-18 (CK-18) (M65 and M30) Levels
timeFrame: Double Blind Period: Baseline, Week 12
measure: 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)
timeFrame: Pre-dose, 0.5 hour (h), 1h, between 1.5 hours and 2h, 4h, and 6h after dosing at Week 4
measure: PK of Elafibranor and its Metabolite GFT1007: Maximum (peak) Observed Plasma Drug Concentration (Cmax)
timeFrame: Pre-dose, 0.5 hour (h), 1h, between 1.5h and 2h, 4h, and 6h after dosing at Week 4
measure: PK of Elafibranor and its Metabolite GFT1007: Time to Maximum Observed Drug Concentration (Tmax)
timeFrame: Pre-dose, 0.5 hour (h), 1h, between 1.5h and 2h, 4h, and 6h after dosing at Week 4
measure: PK of Elafibranor and its Metabolite GFT1007: Total Body Clearance (Cl/F)
timeFrame: Double Blind Period: Baseline up to Week 12
measure: PK of Elafibranor and its Metabolite GFT1007: Volume of distribution (Vz)
timeFrame: Double Blind Period: Baseline up to Week 12
Other outcomes:
Locations:
city: Lancaster
country: United States
facility: Om Research LLC
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Francisco
country: United States
facility: Sutter Health Van Ness Campus Medical Office Building
state: California
city: Colorado Springs
country: United States
facility: Peak Gastroenterology Associates
state: Colorado
city: Englewood
country: United States
facility: South Denver Gastroenterology,P.C.
state: Colorado
city: Littleton
country: United States
facility: Rocky Mountain Gastroenterology (RMG)
state: Colorado
city: New Haven
country: United States
facility: Yale University School Of Medicine - Yale Center For Clinical Investigation
state: Connecticut
city: Miami
country: United States
facility: Schiff Center for Liver Diseases - University of Miami
state: Florida
city: Sarasota
country: United States
facility: Covenant Research
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital - Piedmont Transplant Institute
state: Georgia
city: Marrero
country: United States
facility: Tandem Clinical Research GI
state: Louisiana
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center, Liver Research Center
state: Massachusetts
city: Ypsilanti
country: United States
facility: Huron Gastroenterology Associates - Center for Digestive Care
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Albuquerque
country: United States
facility: Southwest Gastroenterology Associates, PC (SWGA)
state: New Mexico
city: New York
country: United States
facility: New York University Langone Health
state: New York
city: Cincinnati
country: United States
facility: Gastro Health Research
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Cordova
country: United States
facility: Gastro One
state: Tennessee
city: Dallas
country: United States
facility: University Of Texas Southwestern Medical Center At Dallas
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation at The Texas Liver Institute
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Richmond
country: United States
facility: Bon Secours Richmond Community Hospital LLC. d/b/a Bon Secours Liver Institute of Richmond
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Liver Institute Northwest
state: Washington
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University Of Alberta Hospital-Zeidler Ledcor Centre
state: Alberta
city: Brampton
country: Canada
facility: Brampton Civic Hospital (BCH) - Osler Hepatitis Centre
state: Ontario
city: Calgary
country: Canada
facility: Aspen Woods Clinic
city: Montréal
country: Canada
facility: Centre de Recherche du Centre Hospitalier de l'Universite de Montreal
city: Vancouver
country: Canada
facility: G.I Research Institute
city: Berlin
country: Germany
facility: Charite Campus Virchow
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg - Nationales Centrum fuer Tumorerkrankungen
city: Ulm
country: Germany
facility: University Hospital Ulm
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria Modena
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova - U.O.C. di Gastroenterologia
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
city: Rozzano
country: Italy
facility: Gruppo Humanitas - Humanitas Research Hospital, Istituto Clinico Humanitas
city: San Giovanni Rotondo
country: Italy
facility: Ospedale Casa Sollievo della Sofferenza
city: Guimarães
country: Portugal
facility: Centro Hospitalar do Alto Ave - Hospital Senhora da Oliveira
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitario Lisboa Norte
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa ocidental (CHLO), Hospital Egas Moniz
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon (HGUGM)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Pontevedra
country: Spain
facility: Hospital De Montecelo
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary NHS Grampian Grampian Health Board
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Frimley
country: United Kingdom
facility: Frimley Park Hospital - Frimley Health NHS Foundation Trust
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary - Greater Glasgow Health Board
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary - Hull University Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: Ambrose King Centre-Royal London Hospital-Barts Health NHS Trust
city: London
country: United Kingdom
facility: The Royal Free Hospital - Royal Free London NHS Foundation Trust
Study officials:
affiliation: Ipsen
name: Ipsen Medical, Director
role: STUDY_DIRECTOR
References: