Study to Evaluate the Efficacy and Safety of Elafibranor in Patients With Primary Biliary Cholangitis (PBC) and Inadequate Response to Ursodeoxycholic Acid
Condition: Primary Biliary Cholangitis (PBC)
MeSH terms: Cholangitis; Liver Cirrhosis, Biliary
Intervention: Elafibranor 80 mg; Elafibranor 120 mg; Placebo
Intervention description: Two coated tablets daily for 12 weeks; Two coated tablets daily for 12 weeks; Two coated tablets daily for 12 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Elafibranor; Primary Biliary Cholangitis; Alkaline phosphatase

Summary:

      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).
    

Eligibility criteria:

        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)