Primary biliary cholangitis (PBC, formerly known as primary biliary cirrhosis) is a serious and potentially life threatening autoimmune disease of the liver characterized by impaired bile flow (cholestasis) and accumulation of toxic bile acids (BA).
Conditions
Interventions
Product Name: Seladelpar
Product Code: MBX-8025
Pharmaceutical Form: Capsule
INN or Proposed INN: SELADELPAR
CAS Number: 928821-40-3
Concentration unit: mg milligram(s)
Concentration type: equal
Conce
Sponsors
CymaBay Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion 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 6 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 4. On a stable and recommended dose of UDCA for the past 12 months OR intolerant to UDCA (last dose of UDCA > 3 months prior to Screening) 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
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) 7. Serum creatinine above 1.0 × ULN 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 Model for End-Stage Liver Disease (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: a.Current features of auto-immune hepatitis as determined by the investigator based on immunoserology, liver biochemistry and histology b.Primary sclerosing cholangitis determined by presence of diagnostic cholangiographic findings c.History or clinical evidence of alcoholic liver disease d.History or clinical evidence of alpha-1-antitrypsin deficiency e.Biopsy confirmed nonalcoholic steatohepatitis f.History or evidence of Gilbert’ Syndrome with elevated total bilirubin g.History or evidence of hemochromatosis h.Hepatitis B defined as presence of hepatitis B surface antigen (HBsAg) i.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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the safety and effect on cholestasis of two seladelpar regimens (5 mg/day titrated to 10 mg/day and 10 mg/day) over 52 weeks of treatment compared to placebo.;Secondary Objective: Evaluate the effect of seladelpar on normalization of alkaline phosphate (AP) levels and to evaluate the effect of seladelpar on pruritus. Evaluate the effect of seladelpar on quality of life (QoL), to evaluate the effect of seladelpar on other measures of cholestasis, metabolic outcomes, PBC prognosis criteria, and the effect of seladelpar on PBC clinical outcomes.;Primary end point(s): 1 - Response on the composite endpoint of AP and total bilirubin at 12 months: o AP < 1.67 × ULN, o = 15% decrease in AP, and o Total bilirubin = ULN 2 - Assessment of treatment-emergent AEs (TEAEs) (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Version 4.0), biochemistry and hematology;Timepoint(s) of evaluation of this end point: 1- 12 months 2 - Throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - Proportion of patients with AP =1.0 × ULN at 12 months 2 - Change from baseline in pruritus NRS at 6 months;Timepoint(s) of evaluation of this end point: 1 - 12 months 2 - 6 months | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Mexico, Netherlands, New Zealand, Poland, Romania, Russian Federation, Serbia, Spain, United Kingdom, United States
Contacts
Public ContactSenior VP, RA&QA - Klara Dickinson
CymaBay Therapeutics, Inc.
Outcome results
None listed