Study of Elafibranor in Patients With Primary Biliary Cholangitis (PBC)

Study Overview
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Brief Summary
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The main objective of the study is to evaluate the effect of daily oral administration of 80mg elafibranor on cholestasis (impairment of bile formation and/or bile accumulation) in patients with PBC and inadequate response or intolerance to Ursodeoxycholic Acid (UCDA). In the DB period, patients will be randomized in a 2:1 ratio to receive Elafibranor 80 mg or placebo, once daily.

Official Title
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A Double-blind, Randomized, Placebo-Controlled Study and Open-label Long Term Extension to Evaluate the Efficacy and Safety of Elafibranor 80 mg in Patients With Primary Biliary Cholangitis With Inadequate Response or Intolerance to Ursodeoxycholic Acid

Conditions
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Primary Biliary Cirrhosis

Intervention / Treatment
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* Drug: Elafibranor 80mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females age of 18 to 75 years (inclusive) Definite or probable PBC diagnosis ALP ≥ 1.67x upper limit of normal (ULN) Total bilirubin (TB) ≤ 2x ULN UDCA for at least 12 months (stable dose ≥ 3 months) prior to screening, or unable to tolerate UDCA treatment (no UDCA for ≥ 3 months) prior to screening (per country standard-of-care dosing) Females participating in this study must be of non-child bearing potential or must be using highly efficient contraception for the full duration of the study and for 1 month after the last drug intake Exclusion Criteria: History or presence of other concomitant liver disease Clinically significant hepatic decompensation, including patients with cirrhosis/portal hypertension complications Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease) or which may diminish life expectancy to < 2 years, including known cancers Patient has a positive test for Human Immunodeficiency Virus (HIV) Evidence of any other unstable or untreated clinically significant disease History of alcohol abuse For female patients: known pregnancy or lactating Use of fibrates and glitazones within 2 months prior to screening Use of azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids; potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid isoniazid, or nitrofurantoin) within 3 months prior to screening Use of antibodies or immunotherapy directed against interleukins (ILs) or other cytokines or chemokines within 12 months prior to screening For patients with previous exposure to obeticholic acid (OCA), OCA should be discontinued 3 months prior to screening Patients who are currently participating in, plan to participate in, or have participated in an investigational drug study or medical device study containing active substance within 30 days or five half-lives, whichever is longer, prior to screening; for patients with previous exposure to seladelpar, seladelpar should be discontinued 3 months prior to screening. Patients with previous exposure to elafibranor Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 5x ULN Albumin < 3.0 g/dL PBC Severely advanced patients according to Rotterdam criteria (TB > ULN and albumin < LLN) International normalized ratio (INR) > 1.3 due to altered hepatic function Creatine phosphokinase CPK > 2X ULN Serum creatinine > 1.5 mg/dL Significant renal disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a double-blind (DB), randomized, placebo-controlled study followed by an open-label long term extension (LTE)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elafibranor 80mg<br>Study subjects will take 1 tablet per day orally before breakfast with a glass of water each morning | Drug: Elafibranor 80mg<br>* Elafibranor 80mg for double blind period (52 to 104 weeks). After completion of the double blind period, participants will be offered the opportunity to enter an open label long term extension study for up to 5 years. Participants will continue the elafibranor dose received during the double blind period.<br>|
| Placebo Comparator: Placebo<br>Study subjects will take 1 tablet per day orally before breakfast with a glass of water each morning | Drug: Placebo<br>* Placebo for double blind period (52 to 104 weeks). After completion of the double blind period, participants will be offered the opportunity to enter an open label long term extension study and to switch to elafibranor 80mg for up to 5 years.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of elafibranor (80 mg/day) on cholestasis | Response to treatment defined as Alkaline phosphatase (ALP) < 1.67 x Upper Limit Normal (ULN) and Total Bilirubin (TB) ≤ ULN and ALP decrease ≥ 15 percent | From baseline to 52 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to treatment based on ALP normalization |  | At Week 52 | 
| Change in pruritus from baseline in patients with baseline PBC Worst Itch NRS Score ≥ 4 | Based on PBC Worst Itch Numeric Rating Scale (NRS) score measuring itch over the past 24 hours from 0 (no itch) to 10 (worst itch imaginable) | Through 52 weeks of treatment | 
| Change in pruritus from baseline in patients with baseline PBC Worst Itch NRS Score ≥ 4 | Based on PBC Worst Itch Numeric Rating Scale (NRS) score measuring itch over the past 24 hours from 0 (no itch) to 10 (worst itch imaginable) | Through 24 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Biliary Cholangitis, PBC, Elafibranor