Seladelpar (MBX-8025) in Subjects With Primary Biliary Cholangitis (PBC)

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)

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

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 < LLN with the exception to subjects with Gilbert's Syndrome. Subjects with Gilbert's syndrome are excluded if Direct Bilirubin > 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