Elafibranor for adults with primary sclerosing cholangitis

A Phase III, Multicentre, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Elafibranor in Adult Participants With Primary Sclerosing Cholangitis

This trial will see if taking elafibranor once daily helps adults with primary sclerosing cholangitis compared with a placebo.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 350 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Ipsen (industry)
• Locations: 1 site (San Antonio, Texas)
• Trial ID: NCT07387549 on ClinicalTrials.gov

What this trial studies

About 350 adults with large-duct primary sclerosing cholangitis and compensated liver disease will be enrolled and randomized to receive either elafibranor 120 mg once daily or a matching placebo. The protocol includes a screening period, a treatment period with routine clinical assessments, laboratory testing and imaging, and a post-treatment safety follow-up. Participants will complete symptom and quality-of-life questionnaires and undergo evaluations to track liver disease progression and safety. Key exclusions include other chronic liver diseases, prior liver transplant, current hepatic decompensation, recent biliary intervention, and Child-Pugh B/C cirrhosis.

Who should consider this trial

Good fit: Adults (≥18) with confirmed large-duct primary sclerosing cholangitis, compensated liver disease, and stable background therapy who can provide consent and use effective contraception if applicable.

Not a fit: Patients with other chronic liver diseases, prior liver transplantation, current hepatic decompensation, Child-Pugh B or C cirrhosis, high MELD score, or recent biliary intervention are unlikely to qualify or benefit from this trial.

Why it matters

Potential benefit: If effective, elafibranor could slow bile-duct injury and liver disease progression in PSC, potentially delaying the need for transplant and improving symptoms and quality of life.

How similar studies have performed: Elafibranor and other PPAR agonists have been tested in liver conditions like NASH with mixed results, and robust evidence of benefit specifically in PSC is limited.

Eligibility criteria

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.

Exclusion Criteria:

\- History or presence of other concomitant chronic liver disease

\- History of hepatic decompensation, including: i) History of liver transplantation, current MELD 3.0 score ≥12 due to hepatic impairment.

ii) 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 5 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, 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); 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.
* Significant renal disease,
* For female participants: known pregnancy, or has a positive serum pregnancy test, or lactating.
* Regular alcohol intake in excess of the recommended limit of 2 standard drinks per day for men or 1 standard drink per day for women
* History of alcohol abuse, or other substance abuse within 1 year prior to SV.
* Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that contraindicates participation in the study.
* Mental instability or incompetence
* Participant has or is known to have tested positive for human immunodeficiency virus (HIV) type 1 or 2 at SV.
* Medical conditions that may diminish life expectancy to \<2 years.

Where this trial is running

San Antonio, Texas

• American Research Corporation at The Texas Liver Institute — San Antonio, Texas, United States (RECRUITING)

Study contacts

• Study coordinator: Ipsen Clinical Study Enquiries

Conditions: Primary Sclerosing Cholangitis