Seladelpar in Subjects With Primary Biliary Cholangitis (PBC)

• ClinicalTrials.gov Identifier: NCT03301506
• Recruitment Status: Recruiting
• First Posted: October 4, 2017
• Last Update Posted: February 15, 2024
• Sponsor: CymaBay Therapeutics, Inc.
• Information provided by (Responsible Party): CymaBay Therapeutics, Inc.

Tracking Information

• First Submitted Date: September 26, 2017
• First Posted Date: October 4, 2017
• Last Update Posted Date: February 15, 2024
• Actual Study Start Date: December 12, 2017
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 5, 2020): Treatment emergent adverse events (TEAEs) (National Cancer Institute {NCI} Common Terminology Criteria for Adverse Events {CTCAE} Version 5.0), biochemistry and hematology results [ Time Frame: Through study completion, up to 60 Months ]
• Original Primary Outcome Measures (submitted: September 29, 2017): Adverse events (AE) and Treatment Emergent Adverse Events (TEAEs), Biochemistry and Hematology and NCI CTCAE Version 4.0 [ Time Frame: Through study completion, up to 60 Months ]

Current Secondary Outcome Measures (submitted: October 5, 2020)

• Death [ Time Frame: 60 Months ]
  Occurrence of overall death
• Liver transplantation [ Time Frame: 60 Months ]
  Occurrence of overall liver transplantation
• Change in MELD [ Time Frame: 60 Months ]
  MELD score ≥ 15 for at least 2 consecutive visits
• Ascites [ Time Frame: 60 Months ]
  Occurrence of overall ascites requiring treatment
• Hospitalization for variceal bleeding [ Time Frame: 60 Months ]
  Hospitalization for new onset, or recurrence, of variceal bleeding
• Hospitalization for hepatic encephalopathy [ Time Frame: 60 Months ]
  Hospitalization for new onset, or recurrence, hepatic encephalopathy (as defined by a West Haven score ≥ 2)
• Hospitalization for spontaneous bacterial peritonitis [ Time Frame: 60 Months ]
  Hospitalization for new onset, or recurrence, spontaneous bacterial peritonitis (confirmed by culture from diagnostic paracentesis)
• Response on composite endpoint [ Time Frame: 60 Months ]
  Alkaline phosphate (ALP)
• Response on composite endpoint [ Time Frame: 60 Months ]
  Total bilirubin
• Normalization of ALP [ Time Frame: 60 Months ]
  Proportion of subjects with normalization of ALP
• Laboratory Value: Serum Alkaline Phosphatase (ALP) [ Time Frame: Through study completion, up to 60 Months ]
  Serum Alkaline Phosphatase (ALP)
• Laboratory Value: Aspartate Aminotransferase (AST) [ Time Frame: Through study completion, up to 60 Months ]
  Aspartate Aminotransferase (AST)
• Laboratory Value: Alanine Aminotransferase (ALT) [ Time Frame: Through study completion, up to 60 Months ]
  Alanine Aminotransferase (ALT)
• Laboratory Value: Gamma-glutamyl Transferase (GGT) [ Time Frame: Through study completion, up to 60 Months ]
  Gamma-glutamyl Transferase (GGT)
• Laboratory Value: Bilirubin - Total Bilirubin [ Time Frame: Through study completion, up to 60 Months ]
  Bilirubin - Total Bilirubin
• Laboratory Value: Bilirubin - Conjugated Bilirubin [ Time Frame: Through study completion, up to 60 Months ]
  Bilirubin - Conjugated Bilirubin
• Laboratory Value: Bilirubin - Unconjugated Bilirubin [ Time Frame: Through study completion, up to 60 Months ]
  Bilirubin - Unconjugated Bilirubin

Original Secondary Outcome Measures (submitted: September 29, 2017)

• Laboratory Value: Serum Alkaline Phosphatase (AP) [ Time Frame: Through study completion, up to 60 Months ]
  Serum Alkaline Phosphatase (AP)
• Laboratory Value: Aspartate Aminotransferase (AST) [ Time Frame: Through study completion, up to 60 Months ]
  Aspartate Aminotransferase (AST)
• Laboratory Value: Alanine Aminotransferase (ALT) [ Time Frame: Through study completion, up to 60 Months ]
  Alanine Aminotransferase (ALT)
• Laboratory Value: Gamma-glutamyl Transferase (GGT) [ Time Frame: Through study completion, up to 60 Months ]
  Gamma-glutamyl Transferase (GGT)
• Laboratory Value: 5'nucleotidase [ Time Frame: Through study completion, up to 60 Months ]
  5'nucleotidase
• Laboratory Value: Bilirubin - Total Bilirubin [ Time Frame: Through study completion, up to 60 Months ]
  Bilirubin - Total Bilirubin
• Laboratory Value: Bilirubin - Conjugated Bilirubin [ Time Frame: Through study completion, up to 60 Months ]
  Bilirubin - Conjugated Bilirubin
• Laboratory Value: Bilirubin - Unconjugated Bilirubin [ Time Frame: Through study completion, up to 60 Months ]
  Bilirubin - Unconjugated Bilirubin
• Laboratory Value: Bone Specific Alkaline Phosphatase (AP) [ Time Frame: Through study completion, up to 60 Months ]
  Bone Specific Alkaline Phosphatase (AP)
• Laboratory Value: Triglycerides (TG) [ Time Frame: Through study completion, up to 60 Months ]
  Triglycerides (TG)
• Laboratory Value: Total Cholesterol (TC) [ Time Frame: Through study completion, up to 60 Months ]
  Total Cholesterol (TC)
• Laboratory Value: High Density Lipoprotein Cholesterol (HDL-C) [ Time Frame: Through study completion, up to 60 Months ]
  High Density Lipoprotein Cholesterol (HDL-C)
• Laboratory Value: Low Density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Through study completion, up to 60 Months ]
  Low Density Lipoprotein Cholesterol (LDL-C)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Seladelpar in Subjects With Primary Biliary Cholangitis (PBC)
• Official Title: ASSURE: An Open Label Long-Term Study to Evaluate the Safety and Tolerability of Seladelpar in Subjects With Primary Biliary Cholangitis (PBC)
• Brief Summary: An Open Label Long-Term Study to Evaluate the Safety and Tolerability of Seladelpar in Subjects with Primary Biliary Cholangitis (PBC)

Detailed Description

Primary:

To evaluate the long-term safety and tolerability of seladelpar

Secondary:

• To evaluate the long-term efficacy of seladelpar
• To evaluate the effect of seladelpar on patient-reported outcomes (pruritus)

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Primary Biliary Cirrhosis

Intervention

• Drug: Seladelpar 5 mg Capsule
  Subjects will be assigned to a treatment group if tolerability issues noted in the previous study.
  Other Name: MBX-8025
• Drug: Seladelpar 10 mg Capsule
  Subjects will be assigned to a treatment group unless there are tolerability issues.
  Other Name: MBX-8025

Study Arms

• Experimental: Seladelpar 5 mg Capsules
  Intervention: Drug: Seladelpar 5 mg Capsule
• Experimental: Seladelpar 10 mg Capsule
  Intervention: Drug: Seladelpar 10 mg Capsule

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 5, 2020): 500
• Original Estimated Enrollment (submitted: September 29, 2017): 356
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Must have given written informed consent (signed and dated)
2. Participated in a PBC study with seladelpar
3. 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:

Exclusion criteria are only applicable for subjects with a seladelpar interruption greater than 4 weeks prior to Day 1 of this study and for subjects who participated in CB8025-21838 irrespective of seladelpar interruption.

1. Treatment-related adverse event (AE) leading to seladelpar discontinuation in a previous PBC study with 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 or ALT above 3 × the upper limit of normal (ULN)
4. Total bilirubin above 2 × ULN
5. MELD score ≥ 12. For subjects on anticoagulation medication, evaluation of the baseline INR, in concert with any current dose adjustments in anti-coagulant medications, will be taken into account when calculating this score. This will be done in consultation with the medical monitor.
6. Evidence of advanced PBC as defined by the Rotterdam criteria: albumin below 1× the lower limit of normal (LLN) AND total bilirubin above 1 × ULN)
7. eGFR ≤45 mL/min/1.73 m2 (calculated by MDRD formula)
8. Auto-immune hepatitis
9. Primary sclerosing cholangitis
10. Known history of alpha-1-antitrypsin deficiency
11. Known history of chronic viral hepatitis
12. For females, pregnancy or breast-feeding
13. Use of colchicine, methotrexate, azathioprine, or long-term use of systemic steroids (e.g. prednisone, prednisolone, budesonide) (>2 weeks) within 2 months prior to Screening
14. Current use of fibrates or use of fibrates within 3 months prior to Screening
15. Current use of obeticholic acid or use of obeticholic acid within 3 months prior to Screening
16. Use of an experimental or unapproved treatment for PBC within 3 months prior to Screening
17. History of malignancy diagnosed or treated, actively or within 2 years, or active evaluation for malignancy; localized treatment of squamous or non-invasive basal cell skin cancers and cervical carcinoma in-situ is allowed if appropriately treated prior to Screening
18. Treatment with any other investigational therapy or medical device within 30 days or within 5 half-lives, whatever is longer, prior to Screening
19. 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
20. Immunosuppressant therapies (e.g., cyclosporine, tacrolimus, anti-TNF or other immunosuppressive biologics)
21. Other medications that effect liver or GI functions such as absorption of medications or the roux-en-y gastric bypass procedure may be prohibited and should be discussed with the medical monitor on a case-by-case basis

22. Positive for:

    1. Hepatitis B, defined as the presence of hepatitis B surface antigen
    2. Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid (RNA)
    3. Human immunodeficiency virus (HIV) antibody
23. Active COVID-19 infection during screening

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Barry Crittenden, MD; 510-293-8800; medinfo@cymabay.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Canada, Chile, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Mexico, Netherlands, New Zealand, Poland, Romania, Russian Federation, Spain, Switzerland, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT03301506
• Other Study ID Numbers: CB8025-31731
• 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: Not Provided
• Current Responsible Party: CymaBay Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: CymaBay Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: CymaBay Therapeutics, Inc.
• Verification Date: August 2023