seladelpar (mbx-8025) in subjects with primary biliary cholangitis (pbc)

Conditions: Primary Biliary Cirrhosis

Summary: an 8-week, dose ranging, open label, randomized, phase 2 study with a 44-week extension, to evaluate the safety and efficacy of mbx-8025 in subjects with primary biliary cholangitis (pbc) and an inadequate response to or intolerance to ursodeoxycholic acid (udca)

primary: to evaluate the safety and efficacy of mbx-8025 2 mg, 5 mg, and 10 mg over 8 weeks of treatment secondary: to evaluate the safety and efficacy of mbx-8025 2 mg, 5 mg, and 10 mg over 12 and 26 weeks of treatment to evaluate the safety and efficacy of mbx-8025 2 mg, 5 mg, and 10 mg over 52 weeks of treatment to evaluate the pharmacokinetics (pk) of mbx-8025 exploratory: to evaluate the effect of mbx-8025 on bile acids, additional markers of inflammation and renal function mbx-8025 doses of 1 mg and 15 mg may be evaluated if dose adjustment occurs

Eligibility criteria:
inclusion criteria: 1. must have given written informed consent (signed and dated) and any authorizations required by local law 2. 18 to 75 years old (inclusive) 3. 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 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 4. on a stable and recommended dose of udca for the past twelve months or intolerant to udca 5. ap ≥ 1.67 × uln 6. 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: 1. 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 on active treatment) 2. ast or alt \> 3 × uln 3. total bilirubin \> 2.0 mg/dl 4. total bilirubin \> uln and albumin \ uln. 5. auto-immune hepatitis 6. primary sclerosing cholangitis 7. known history of alpha-1-antitrypsin deficiency 8. known history of chronic viral hepatitis 9. creatine kinase above uln 10. serum creatinine above uln 11. for females, pregnancy or breast-feeding 12. use of colchicine, methotrexate, azathioprine, or systemic steroids in the two months preceding screening 13. current use of fibrates or simvastatin 14. current use of obeticholic acid 15. use of an experimental or unapproved treatment for pbc 16. use of experimental or unapproved immunosuppressant 17. adverse event leading to mbx-8025 discontinuation from cymabay's phase 2 pbc study (cb8025-21528) 18. 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

Keywords: pbc primary biliary cholangitis (pbc)