ENHANCE: Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA)

Exclusion Criteria

• •1. Previous exposure to seladelpar (MBX-8025)
• •2. A medical condition, other than PBC, that in the investigator's opinion would preclude full participation in the study or confound its results (e.g., cancer)
• •3. AST above 3 × ULN
• •4. ALT above 3 × ULN
• •5. Total bilirubin above 2.0 × ULN
• •6. Advanced PBC as defined by the Rotterdam criteria (albumin below LLN AND total bilirubin above 1 × ULN)
• •7. Creatine kinase (CK) above 1.0 × ULN
• •8. eGFR below 60 mL/min/1.73 m2 (calculated by MDRD formula)
• •9. International normalized ratio (INR) above 1.0 × ULN
• •10. Platelet count below 100 × 103/µL
• •11. Presence of clinically significant hepatic decompensation, including:
• •* History of liver transplantation, current placement on liver transplantation list, or current MELD score ≥ 15
• •* Complications of portal hypertension, including known esophageal varices, history of variceal bleeds or related interventions (e.g., transjugular intrahepatic portosystemic shunt placement), relevant ascites, hepatic encephalopathy
• •* Cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis
• •12. Other chronic liver diseases:
• •* Current features of auto-immune hepatitis as determined by the investigator based on immunoserology, liver biochemistry and histology
• •* Primary sclerosing cholangitis determined by presence of diagnostic cholangiographic findings
• •* History or clinical evidence of alcoholic liver disease
• •* History or clinical evidence of alpha-1-antitrypsin deficiency
• •* Biopsy confirmed nonalcoholic steatohepatitis
• •* History or evidence of Gilbert' Syndrome with elevated total bilirubin
• •* History or evidence of hemochromatosis
• •* Hepatitis B defined as presence of hepatitis B surface antigen (HBsAg)
• •* Hepatitis C defined as presence of HCV RNA
• •13. Known history of HIV
• •14. Evidence of significant alcohol consumption
• •15. Evidence of drug abuse
• •16. Subjects with inadequate response to obeticholic acid (OCA) or intolerance to OCA: OCA must be discontinued 30 days prior to Screening
• •17. Use of colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (\> 2 weeks) within two months prior to Screening
• •18. Use of fibrates within 30 days prior to Screening
• •19. Use of simvastatin within 7 days prior to Screening
• •20. Use of an experimental or unapproved treatment for PBC within 30 days prior to Screening
• •21. Use of experimental or unapproved immunosuppressant within 30 days prior to Screening
• •22. Treatment with any other investigational therapy or device within 30 days or within five half-lives, whatever is longer, prior to Screening
• •23. For females, pregnancy or breast-feeding
• •24. Any other condition(s) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the investigator