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

• Register: ClinicalTrials.gov
• Last refreshed on: 9 June 2025
• Main ID: NCT05627362
• Date of registration: 22/11/2022
• Prospective Registration: Yes
• Primary sponsor: Ipsen
• Public title: A Study to Assess Safety and Effectiveness of Elafibranor in Adult Participants With Primary Sclerosing Cholangitis. ELMWOOD
• Scientific 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).
• Date of first enrolment: December 29, 2022
• Target sample size: 68
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT05627362
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

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

Contacts

• Name: Ipsen Medical, Director
• Affiliation: Ipsen

Key inclusion & exclusion 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


Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Primary Sclerosing Cholangitis

Intervention(s)

Drug: Elafibranor 80 mg

Drug: Placebo Matched to Elafibranor 120 mg

Drug: Placebo Matched to Elafibranor 80 mg

Drug: Elafibranor 120 mg

Primary Outcome(s)

Percentage of Participants With Clinically Significant Changes in Vital Signs [Time Frame: Double Blind Period: Baseline up to week 12, OLE Period: Baseline up to week 100]

Percentage of Participants With Treatment Emergent Adverse Event (TEAEs), Treatment Related TEAEs, Serious Adverse (SAEs) and Adverse Events of Special Interest (AESIs) [Time Frame: 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 [Time Frame: 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 [Time Frame: 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) [Time Frame: Double Blind Period: Baseline up to week 12, OLE Period: Baseline up to week 100]

Secondary Outcome(s)

Change From Baseline in Alanine Transaminase (ALT),Aspartate Transaminase (AST), Gamma-glutamyl transferase (GGT), 5' Nucleotidase and Fractionated ALP Levels at Week 12 [Time Frame: Baseline, Week 12]

Change From Baseline in Albumin Levels at Week 12 [Time Frame: Baseline, Week 12]

Change From Baseline in Cytokeratin-18 (CK-18) (M65 and M30) Levels [Time Frame: Double Blind Period: Baseline, Week 12]

Change From Baseline in Fibrosis-4 (FIB-4) and AST to Platelet Ratio Index (APRI) [Time Frame: Double Blind Period: Baseline, Week 12]

Change from Baseline in Enhanced Liver Fibrosis (ELF) Test Score [Time Frame: Double Blind Period: Baseline, Week 12]

Change From Baseline in Liver Stiffness Measurement (LSM) Values Assessed by FibroScan® at Week 12 [Time Frame: Double Blind Period: Baseline, Week 12]

Percentage of Participants With ALP: <1.3x Upper Limit of Normal (ULN) and <1.5x ULN [Time Frame: Double Blind Period: Week 12]

PK of Elafibranor and its Metabolite GFT1007: Total Body Clearance (Cl/F) [Time Frame: Double Blind Period: Baseline up to Week 12]

Percentage of Participants With =40% Decrease from Baseline in ALP Levels [Time Frame: Double Blind Period: Baseline, Week 12, OLE Period: Baseline, Week 52, Week 96]

Relative Change From Baseline in Alkaline Phosphate Levels (ALP) [Time Frame: Double Blind Period: Baseline, Week 12, OLE Period: Baseline, Week 52, Week 96]

Percentage of Participants who Normalised ALP [Time Frame: Double Blind Period: Week 12]

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) [Time Frame: Double Blind Period: Baseline, Week 12]

Absolute Change from Baseline in ALP [Time Frame: Double Blind Period: Baseline, Week 12, OLE Period: Baseline, Week 52, Week 96]

Change From Baseline in Total bilirubin, Conjugated bilirubin Levels at Week 12 [Time Frame: 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) [Time Frame: 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) [Time Frame: 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) [Time Frame: 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: Volume of distribution (Vz) [Time Frame: Double Blind Period: Baseline up to Week 12]

Secondary ID(s)

CLIN-60190-453

2022-002695-37

Source(s) of Monetary Support

Please refer to primary and secondary sponsors