Purpose

A 52-week, placebo-controlled, randomized, Phase 3 study to evaluate the safety and efficacy of seladelpar in subjects with primary biliary cholangitis (PBC) and an inadequate response to or intolerance to ursodeoxycholic acid (UDCA)

Condition

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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:
  4. History of AP above ULN for at least six months
  5. 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
  6. Documented liver biopsy result consistent with PBC
  7. 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)
  8. AP ≥ 1.67 × ULN
  9. 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. 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)
  9. International normalized ratio (INR) above 1.0 × ULN
  10. Platelet count below 100 × 103/µL
  11. Presence of clinically significant hepatic decompensation, including:
  12. History of liver transplantation, current placement on liver transplantation list, or current MELD score ≥ 15
  13. 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
  14. Cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis
  15. Other chronic liver diseases:
  16. Current features of auto-immune hepatitis as determined by the investigator based on immunoserology, liver biochemistry and histology
  17. Primary sclerosing cholangitis determined by presence of diagnostic cholangiographic findings
  18. History or clinical evidence of alcoholic liver disease
  19. History or clinical evidence of alpha-1-antitrypsin deficiency
  20. Biopsy confirmed nonalcoholic steatohepatitis
  21. History or evidence of Gilbert' Syndrome with elevated total bilirubin
  22. History or evidence of hemochromatosis
  23. Hepatitis B defined as presence of hepatitis B surface antigen (HBsAg)
  24. Hepatitis C defined as presence of HCV RNA
  25. Known history of HIV
  26. Evidence of significant alcohol consumption
  27. Evidence of drug abuse
  28. Subjects with inadequate response to obeticholic acid (OCA) or intolerance to OCA: OCA must be discontinued 30 days prior to Screening
  29. Use of colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (> 2 weeks) within two months prior to Screening
  30. Use of fibrates within 30 days prior to Screening
  31. Use of simvastatin within 7 days prior to Screening
  32. Use of an experimental or unapproved treatment for PBC within 30 days prior to Screening
  33. Use of experimental or unapproved immunosuppressant within 30 days prior to Screening
  34. Treatment with any other investigational therapy or device within 30 days or within five half-lives, whatever is longer, prior to Screening
  35. For females, pregnancy or breast-feeding
  36. 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Seladelpar 5-10 mg
  • Drug: seladelpar 5-10 mg
    Seladelpar 5 mg for 6 months and then titrating up to 10 mg based on tolerability and response for remainder of double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label long term safety study. Subjects will continue the seladelpar dose (5 or 10 mg) received during the double-blinded study
Experimental
Seladelpar 10 mg
  • Drug: seladelpar 10 mg
    Seladelpar 10 mg for double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label safety study. Subjects will continue the seladelpar dose (10 mg) received during the double-blinded study
Placebo Comparator
Placebo
  • Drug: Placebo
    One capsule daily for double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label long term safety study. Subjects on placebo will be re-randomized to initiate seladelpar at 5 or 10 mg once daily

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Arley Donovan
617-726-0161
adonovan14@mgh.harvard.edu

More Details

NCT ID
NCT03602560
Status
Recruiting
Sponsor
CymaBay Therapeutics, Inc.

Study Contact

Pol F Boudes, MD
510-293-8815
PBoudes@cymabay.com

Detailed Description

Primary:

• To 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

Key Secondary:

- To evaluate the effect of seladelpar on normalization of alkaline phosphatase (AP) levels

- To evaluate the effect of seladelpar on pruritus

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.