Phase III Randomized Double‑Blind Placebo‑Controlled Study of Oral Elafibranor 120 mg in Adults with Primary Sclerosing Cholangitis

Trial ID: 2026-525242-29-00
Protocol: CLIN-60190-475
Sponsor: Ipsen Bioscience Inc.

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Diseases & Conditions

Cholangitis sclerosing

Objectives

The primary objective is to determine whether daily oral administration of elafibranor 120 mg improves the time to first occurrence of a predefined clinical outcome event compared with placebo in adults with Primary Sclerosing Cholangitis, thereby assessing therapeutic efficacy in this rare cholestatic liver disease.

Participants

The trial enrolled a total of 223 adult participants aged 18 years or older, comprising both female and male individuals with a confirmed diagnosis of Primary Sclerosing Cholangitis based on standard clinical, biochemical, and imaging criteria. All subjects had compensated liver disease at screening and were on stable background therapy when applicable. Women of child‑bearing potential were required to use a highly effective contraceptive method throughout the study, and all participants were required to provide written informed consent and adhere to study procedures. The population included patients without restriction to vulnerable subgroups, reflecting a broad adult patient cohort.

Plans and Procedures

The study is a multicentre, Phase III, randomized, double‑blind, placebo‑controlled trial evaluating the efficacy and safety of daily oral elafibranor 120 mg compared with a matching placebo in adult participants with Primary Sclerosing Cholangitis. After an initial screening visit to confirm eligibility, participants are randomized in a 1:1 ratio to receive either elafibranor or placebo for the duration of the trial, which spans approximately five years from the projected start date (July 2026) to the projected end date (July 2031). Subsequent follow‑up visits are scheduled throughout the treatment period to monitor clinical status, laboratory parameters, and adverse events, culminating in a final end‑of‑study visit after the last dose. Participant involvement therefore extends from screening through to the end‑of‑study assessment, encompassing the full treatment period. The primary endpoint is event‑free survival, defined as the time from randomisation to the first occurrence of adjudicated clinical outcome events such as all‑cause mortality, liver transplantation, hepatic decompensation, portal hypertension syndromes, or cholangiopathy‑related events.

Treatment

The investigational product is elafibranor, supplied as a film‑coated tablet for oral administration. Each tablet contains 120 mg of the active substance. The dosing regimen consists of one tablet taken once daily with water, without regard to meals. The product is classified as an orphan drug and is provided in identical packaging to the control product to maintain blinding.

The control arm receives a placebo that is otherwise identical to the investigational product in appearance, packaging, and labeling. The placebo contains no active pharmaceutical ingredient and is administered using the same route, dosage form, and schedule as the active treatment.

Both study medications are dispensed in a blinded manner at the start of each treatment cycle. Participants are instructed to record each dose in a medication diary and to return all unused tablets at scheduled visits. Tablet counts and diary entries are used to assess compliance, with a compliance threshold of ≥80 % of prescribed doses required for inclusion in the per‑protocol analysis. Dosing adjustments are not permitted; missed doses are documented, and participants are advised to resume the regular dosing schedule at the next scheduled intake.

Efficacy

The efficacy assessment is based on the primary endpoint of event‑free survival, defined as the time from randomisation to the first occurrence of any adjudicated clinical outcome event, including all‑cause mortality, liver transplantation, hepatic decompensation, portal hypertension syndromes, or cholangiopathy‑related events.

Time‑to‑event data will be collected continuously from the date of randomisation throughout the treatment period. Events are identified and confirmed by a blinded clinical events committee according to predefined criteria. Survival analysis methods, such as Kaplan–Meier estimation and Cox proportional hazards modeling, will be employed to compare the elafibranor 120 mg group with placebo.

The study population comprises adult participants with Primary Sclerosing Cholangitis who meet the inclusion criteria.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Adults participants aged 18 years or older.
Confirmed diagnosis of primary sclerosing cholangitis based on standard clinical, biochemical, and imaging criteria
Compensated liver disease at screening
Stable background therapy, where applicable prior to study entry
Women of childbearing potential have to apply during the entire duration of the study a highly effective method of birth control
Ability to provide written informed consent and comply with study procedures.

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Exclusion Criteria

History or presence of other concomitant chronic liver disease
Presence of hepatitis B surface antigen at SV, or hepatitis C virus (HCV) infection defined by positive anti-HCV antibody and positive HCV ribonucleic acid (RNA)
History of hepatic decompensation, including: i) History of liver transplantation, ii) Current MELD 3.0 score ≥12 due to hepatic impairment, iii) Evidence of complications of cirrhosis.
Participants with cirrhosis who are also classified as Child-Pugh B or C based on the Child-Pugh score.
History of biliary intervention within 60 days prior to the screening period, and/or presence of percutaneous drain or bile duct stent at SV.
History of bacterial cholangitis, and/or participant on antibiotics for prophylaxis of recurrent cholangitis within 60 days prior to the SV.
History or any current suspicion of cholangiocarcinoma or Hepatocellular carcinoma
Known malignancy or history of malignancy within the last five years, with the exception of local, successfully treated basal cell carcinoma or in-situ carcinoma of the uterine cervix.
Medical conditions that may cause non-hepatic increases in ALP (e.g. Paget’s disease).
Administration of the following medications are prohibited as specified below: i) 3 months prior to baseline: norucholic acid, ileal bile acid transportinhibitors, fibrates, seladelpar and glitazones. ii) 3 months prior to baseline: cyclosporine, mycophenolate, pentoxifylline, and chronic systemic corticosteroids (except as part of management of IBD at an ongoing stable dose and as part of management of adrenal insufficiency as specified in Appendix 10.5.2); potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin).
Participants who are currently participating in, plan to participate in, or have participated in an investigational drug or medical device study containing active substance within 30 days or five half-lives, whichever is longer, prior to the SV.
Participants with previous exposure to elafibranor.
Electrocardiogram (ECG) with QT interval corrected by Fridericia’s formula (QTcF) > 450 msec in males or QTcF >470 msec in females for participants without bundle branch block. For participants with bundle branch block or other intraventricular conduction delay, a longer QTcF >480 msec would be exclusionary.
Liver related laboratory tests.
Significant renal disease
Creatine phosphokinase (CPK) >2× ULN during SV.
For female participants: known pregnancy, or has a positive serum pregnancy test, or lactating.
Regular alcohol intake in excess of the recommended limit of two standard drinks per day for men or one standard drink per day for women
History of alcohol abuse, or other substance abuse within one year prior to SV.
Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study.
Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.
Participant has or is known to have tested positive for human immunodeficiency virus (HIV) type 1 or 2 at SV.
Other medical conditions that may diminish life expectancy to <2 years.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Austria	Not Yet Recruiting	15 Jul 2026	2
Belgium	Not Yet Recruiting	15 Jul 2026	8
Czechia	Not Yet Recruiting	15 Jul 2026	6
Denmark	Not Yet Recruiting	15 Jul 2026	8
Finland	Not Yet Recruiting	15 Jul 2026	2
France	Not Yet Recruiting	15 Jul 2026	14
Germany	Not Yet Recruiting	15 Jul 2026	14
Italy	Not Yet Recruiting	15 Jul 2026	7
The Netherlands	Not Yet Recruiting	15 Jul 2026	—
Norway	Not Yet Recruiting	15 Jul 2026	6