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

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).

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