Primary Biliary Cholangitis MedDRA version: 21.0 Level: LLT Classification code 10036680 Term: Primary biliary cirrhosis System Organ Class: 100000004871
Conditions
Interventions
Product Name: Seladelpar
Product Code: MBX-8025
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: SELADELPAR
CAS Number: 928821-40-3
Current Sponsor code: MBX-8025
Concentration unit: mg milligr
Sponsors
CymaBay Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Must have given informed consent (signed and dated) 2. Participated in a prior PBC study with seladelpar (e.g., including CB8025-21629, CB8025-31735, or CB8025-31731), current PBC studies (CB8025-32048 or CB8025-21838), or completed a future PBC study with seladelpar that allows rollover into CB8025-31731-RE, and meet eligibility criteria for the current study. 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 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 428 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 72
Exclusion criteria
Exclusion criteria: Exclusion criteria are only applicable for subjects with a study drug 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 AE leading to study drug discontinuation in a previous PBC study with seladelpar 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, any active infection) 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 × lower limit of normal AND total bilirubin above 1 × ULN) 7. Estimated glomerular filtration rate = 45 mL/min/1.73 m2 (calculated by Modification of Diet in Renal Disease 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. See the concomitant medication section for additional medications that may be excluded. 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 may be prohibited and should be discussed with the medical monitor on a case-by-case basis 22. Positive for: a. Hepatitis B, defined as the presence of hepatitis B surface antigen b. Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid c. Human immunodeficiency virus (HIV) antibody 23. Active COVID-19 infection during Screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Treatment-emergent AEs (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Version 5.0), biochemistry and hematology results are collected;Timepoint(s) of evaluation of this end point: Throughout the study;Main Objective: To evaluate the long-term safety and tolerability of seladelpar;Secondary Objective: To evaluate the long-term efficacy of seladelpar, and the effect of seladelpar on patient-reported outcomes (pruritus) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Occurrence of the following adjudicated PBC clinical outcomes: -Overall death -Liver transplantation -MELD score = 15 for at least 2 consecutive visits -Ascites requiring treatment -Hospitalization for new onset or recurrence, of any: -Variceal bleeding, Hepatic encephalopathy (as defined by a West Haven score = 2), Spontaneous bacterial peritonitis (confirmed by culture from diagnostic paracentesis) 2. Biochemical markers: -Response on composite of ALP and total bilirubin -Proportion of subjects with normalization of ALP 3.Relative and absolute changes of ALP, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase, bilirubin (total, direct, indirect), 4.Change from Baseline in pruritus numerical rating scale (NRS);Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
Argentina, Australia, Austria, Belgium, Canada, Chile, Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Mexico, Netherlands, New Zealand, Poland, Romania, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactElaine Watkins
CymaBay Therapeutics, Inc.
Outcome results
None listed