Intervention: Seladelpar
Trial phase: Phase 3
SMILES: CCO[C@H](COc1ccc(C(F)(F)F)cc1)CSc1ccc(OCC(=O)O)c(C)c1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 89
Group description: Seladelpar 10 mg in this double-blinded study
Eligibility criteria:
Inclusion Criteria:

Must have given written informed consent (signed and dated) and any authorizations required by local law
18 to 75 years old (inclusive)

Male or female with a diagnosis of PBC, by at least two of the following criteria:

History of AP above ULN for at least six months
Positive anti-mitochondrial antibody (AMA) titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay [ELISA]) or positive PBC-specific antinuclear antibodies
Documented liver biopsy result consistent with PBC
On a stable and recommended dose of UDCA for the past twelve months OR intolerant to UDCA (last dose of UDCA > 3 months prior to Screening)
AP ≥ 1.67 × ULN
Females of reproductive potential must use at least one barrier contraceptive and a second effective birth control method during the study and for at least 90 days after the last dose. Male subjects who are sexually active with female partners of reproductive potential must use barrier contraception and their female partners must use a second effective birth control method during the study and for at least 90 days after the last dose

Exclusion Criteria:

Previous exposure to seladelpar (MBX-8025)
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)
AST above 3 × ULN
ALT above 3 × ULN
Total bilirubin above 2.0 × ULN
Advanced PBC as defined by the Rotterdam criteria (albumin below LLN AND total bilirubin above 1 × ULN)
Creatine kinase (CK) above 1.0 × ULN
eGFR below 60 mL/min/1.73 m2 (calculated by MDRD formula)
International normalized ratio (INR) above 1.0 × ULN
Platelet count below 100 × 103/µL

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

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
Known history of HIV
Evidence of significant alcohol consumption
Evidence of drug abuse
Subjects with inadequate response to obeticholic acid (OCA) or intolerance to OCA: OCA must be discontinued 30 days prior to Screening
Use of colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (> 2 weeks) within two months prior to Screening
Use of fibrates within 30 days prior to Screening
Use of simvastatin within 7 days prior to Screening
Use of an experimental or unapproved treatment for PBC within 30 days prior to Screening
Use of experimental or unapproved immunosuppressant within 30 days prior to Screening
Treatment with any other investigational therapy or device within 30 days or within five half-lives, whatever is longer, prior to Screening
For females, pregnancy or breast-feeding
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