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ENHANCE: Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA)

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ClinicalTrials.gov Identifier: NCT03602560
Recruitment Status : Suspended (unexpected histological findings in a phase 2 study in NASH patients CB8025-21730)
First Posted : July 27, 2018
Last Update Posted : December 11, 2019
Sponsor:
Information provided by (Responsible Party):
CymaBay Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE July 18, 2018
First Posted Date  ICMJE July 27, 2018
Last Update Posted Date December 11, 2019
Actual Study Start Date  ICMJE November 26, 2018
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2018)
Composite endpoint of AP and total bilirubin [ Time Frame: 12 months ]
  • AP < 1.67 × ULN,
  • ≥ 15% decrease in AP, and
  • Total bilirubin ≤ ULN
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ENHANCE: Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA)
Official Title  ICMJE 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 an Intolerance to Ursodeoxycholic Acid (UDCA)
Brief Summary 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)
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Primary Biliary Cholangitis
Intervention  ICMJE
  • 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
  • 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
  • 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
Study Arms  ICMJE
  • Experimental: Seladelpar 5-10 mg
    Intervention: Drug: seladelpar 5-10 mg
  • Experimental: Seladelpar 10 mg
    Intervention: Drug: seladelpar 10 mg
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: July 18, 2018)
240
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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 twelve 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

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:

    • History of liver transplantation, current placement on liver transplantation list, or current 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:

    • Current features of auto-immune hepatitis as determined by the investigator based on immunoserology, liver biochemistry and histology
    • Primary sclerosing cholangitis determined by presence of diagnostic cholangiographic findings
    • History or clinical evidence of alcoholic liver disease
    • History or clinical evidence of alpha-1-antitrypsin deficiency
    • Biopsy confirmed nonalcoholic steatohepatitis
    • History or evidence of Gilbert' Syndrome with elevated total bilirubin
    • History or evidence of hemochromatosis
    • Hepatitis B defined as presence of hepatitis B surface antigen (HBsAg)
    • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   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
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03602560
Other Study ID Numbers  ICMJE CB8025-31735
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CymaBay Therapeutics, Inc.
Study Sponsor  ICMJE CymaBay Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account CymaBay Therapeutics, Inc.
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP