Seladelpar (MBX-8025) in Subjects With Primary Biliary Cholangitis (PBC)
Condition: Primary Biliary Cirrhosis
MeSH terms: Cholangitis; Liver Cirrhosis, Biliary
Intervention: MBX-8025 2 mg Capsule; MBX-8025 5 mg Capsule; MBX-8025 10 mg Capsule
Intervention description: Initial 8-week treatment:
• MBX-8025 2 mg
Extension:
The 2 mg group will be started after safety and efficacy review of the 5 mg and the 10 mg groups has been completed.
Subjects will initially enter the extension on their assigned dose. The dose might be up- or down-titrated after safety and efficacy data review of the first 8 weeks of treatment. During the extension, a subject's dose might be re-adjusted for safety or efficacy reasons.; Initial 8-week treatment:
• MBX-8025 5 mg
Extension:
Subjects will initially enter the extension on their assigned dose. The dose might be up- or down-titrated after safety and efficacy data review of the first 8 weeks of treatment. During the extension, a subject's dose might be re-adjusted for safety or efficacy reasons.; Initial 8-week treatment:
• MBX-8025 10 mg
Extension:
Subjects will initially enter the extension on their assigned dose. The dose might be up- or down-titrated after safety and efficacy data review of the first 8 weeks of treatment. During the extension, a subject's dose might be re-adjusted for safety or efficacy reasons.
Intervention MeSH terms: Seladelpar
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 119.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: PBC; Primary Biliary Cholangitis (PBC)

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)
    

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 < 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