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


About this study

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).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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)
    • Liver biopsy consistent with PBC
  3. ALP ≥ 1.67x upper limit of normal (ULN) (‘inadequate response to UDCA’)
  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:
    • Positive hepatitis B surface antigen (HBsAg) at Screening
    • Positive HCV RNA (tested for in case of known cured HCV infection, or positive
    • HCV Ab at Screening)
    • Alcoholic liver disease
    • Primary sclerosing cholangitis (PSC)
    • Definite autoimmune hepatitis (AIH), or ‘AIH-PBC overlap syndrome’; (the existence of) AIH is defined as continuing use of budesonide or other systemic corticosteroid therapy, and/or azathioprine, and/or other immunosuppressive therapy following an historical AIH diagnosis (EASL 2015). ‘AIH-PBC overlap syndrome’ is based upon fulfilment of the Paris criteria (Chazouilléres 1998)for both AIH (ALT ≥5x ULN; IgG ≥2x ULN or smooth muscle antibody; interface hepatitis), and PBC (ALP ≥2x ULN; AMA, and non-suppurative bile duct injury/destruction),, and requiring corticosteroid therapy for disease management, either currently or in the past.

  2. Biopsy confirmed Nonalcoholic Steatohepatitis NASH)
  3. Known history of alpha-1 antitrypsin deficiency, or other metabolic forms of chronic liver disease.
  4. Gilbert's Syndrome (due to interpretability of bilirubin levels)
  5. Screening CPK > ULN
  6. Screening ALT or AST > 5 ULN
  7. Screening total bilirubin > 2 ULN
  8. Screening serum creatinine > 1.5 mg/dl and eGFR < 60 mL/min/1.73 m2,
  9. 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 m2).
  10. Patients with moderate or severe hepatic impairment (defined as Child-Pugh B/C)
  11. Platelet count <150 X 10 3/microliter
  12. Albumin <3.5 g/dL
  13. Presence of clinical complications of PBC or clinically significant hepatic decompensation, including:
    • Current Model for End-Stage Liver Disease score ≥15; current placement on a liver transplant waiting list, or history of undergoing liver transplantation.
    • Any record of complications of cirrhosis and/or portal hypertension such as:
    • Gastroesophageal variceal bleeding and endoscopic therapy and/or transjugular intrahepatic portosystemic shunt [TIPS] insertion
    • Ascites formation requiring intervention, e.g. diuretic therapy
    • Spontaneous bacterial peritonitis
    • Hepatic encephalopathy
    • Confirmed or suspected hepatocellular carcinoma
  14. If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
  15. Known history of human immunodeficiency virus (HIV) infection
  16. Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease)
  17. Hepatorenal syndrome (type I or II) Administration of the following medications is prohibited as specified below:
    • From pre-randomization to EOT or V5 visit : indomethacin
    • 2 months preceding screening throughout the trial (up to last study visit) : fibrates or obeticholic acid, thiazoledinediones (glitazones)
    • 3 months prior to screening and throughout the trial (up to last study visit) : azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate mofetil, pentoxifylline; budesonide and other chronic systemic corticosteroids; and potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin)
    • 12 months prior to inclusion visit and throughout the trial (up to last study visit): antibodies or immunotherapy directed against interleukins or other cytokines or chemokines NOTE : Anti-pruritus treatment, including rifamycin, is allowed if prescribed for at least 6 months prior to screening, and on stable dose at least 3 months prior to screening. and continues at the same dose throughout the study

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Elizabeth Carey, M.D.

Closed for enrollment

More information


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