Study to Evaluate the Efficacy and Safety of Elafibranor in Patients With Primary Biliary Cholangitis (PBC) and Inadequate Response to Ursodeoxycholic Acid

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Elafibranor at Doses of 80 mg and 120mg After 12 Weeks of Treatment in Patients With Primary Biliary Cholangitis and Inadequate Response to Ursodeoxycholic Acid

The primary objective of the study is to compare the effect of daily oral administration of elafibranor 80mg and 120 mg on change in serum alkaline phosphatase (ALP) to that of placebo in patients with PBC and inadequate response to Ursodeoxycholic acid (UDCA).

Inclusion Criteria:

1. Must have provided written informed consent

2. Definite or probable PBC diagnosis as demonstrated by the presence of at least 2 of the following 3 diagnostic factors:

   • History of elevated ALP levels for at least 6 months prior to Day 0 (randomization visit)
   • Positive Anti-Mitochondrial Antibodies (AMA) titers (> 1/40 on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies
   • Liver biopsy consistent with PBC

3. ALP >= 1.67x upper limit of normal (ULN)

4. Taking UDCA for at least 12 months (stable dose for ≥ 6 months) prior to screening visit

5. Contraception: Females participating in this study must be of non-childbearing potential or must be using highly efficient contraception for the full duration of the study and for 1 month after the end of treatment.

Exclusion Criteria:

1. History or presence of other concomitant liver diseases
2. Screening creatine phosphokinase (CPK) > upper limits of normal (ULN)
3. Screening alanine transaminase (ALT) or aspartate aminotransferase (AST) > 5 ULN
4. Screening total bilirubin > 2 ULN
5. Screening serum creatinine > 1.5 mg/dl
6. Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as patients with markers of kidney damage or estimated glomerular filtration rate [eGFR] of less than 60 mL/min/1.73 m^2).
7. Patients with moderate or severe hepatic impairment (defined as Child-Pugh B/C)
8. Platelet count <150 X 10^3/microliter
9. Albumin <3.5 g/dL
10. Presence of clinical complications of PBC or clinically significant hepatic decompensation
11. If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
12. Known history of human immunodeficiency virus (HIV) infection
13. Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease)