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, hard
INN or Proposed INN: SELADELPAR
CAS Number: 928821-40-3
Current Sponsor code: MBX-8025
Concentration unit: mg millig
Sponsors
CymaBay Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be eligible for study participation: 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 based on any two of the following criteria: a. History of ALP above 1.0× ULN for at least 6 months b. Positive AMA titer (>1:40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay [ELISA]) or positive PBC-specific antinuclear antibodies (ANAs) c. Documented liver biopsy results consistent with PBC 4. UDCA for the past 12 months (stable dose for >3 months prior to screening) OR intolerant to UDCA (last dose of UDCA >3 months prior to screening) 5. Laboratory parameters measured by the Central Laboratory at screening: a. ALP =1.67× ULN b. Aspartate aminotransferase (AST) =3× ULN c. ALT =3× ULN d. Total bilirubin =2× ULN e. Estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m2 (calculated by the Modification of Diet in Renal Disease study equation) f. International normalized ratio (INR) below 1.1× ULN For subjects on anticoagulation therapy, INR must be maintained in the range required for prophylaxis for their specific disease. g. Platelet count =100×103/µL NOTE: PT, INR, and platelets can be performed locally at the Screening Visit, if deemed necessary by the investigator after consultation with the medical monitor, in cases where centrally read samples are deemed invalid 6. Females of reproductive potential (refer to Section 8.1.1) must use at least 1 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 125 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
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 (e.g., cancer) or confound its results (e.g., Paget's disease, any active infection) 3. Advanced PBC as defined by the Rotterdam criteria (albumin below the lower limit of normal AND total bilirubin above 1.0× ULN) 4. Presence of clinically important hepatic decompensation, including the following: a. History of liver transplantation, current placement on liver transplantation list, or current Model for End-Stage Liver Disease (MELD) score =12. For subjects on anticoagulation medication, evaluation of the baseline INR, in concert with their current dose adjustments of their anticoagulant medication, will be taken into account when calculating the MELD score. This will be done in consultation with the medical monitor. b. Complications of portal hypertension, including known esophageal varices, history of variceal bleeds or related interventions (e.g., transjugular intrahepatic portosystemic shunt placement), ascites, and hepatic encephalopathy c. Cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis, hepatocellular carcinoma, or hepatorenal syndrome 5. Other chronic liver diseases: a. Current features of autoimmune hepatitis as determined by the investigator based on immunoserology, liver biochemistry, or historic confirmed liver histology b. Primary sclerosing cholangitis determined by the 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. History of biopsy confirmed NASH f. History or evidence of Gilbert's syndrome with elevated total bilirubin g. History or evidence of hemochromatosis h. Hepatitis B, defined as the presence of hepatitis B surface antigen (HBsAg) i. Hepatitis C, defined as the presence of hepatitis C virus (HCV) ribonucleic acid (RNA) j. History, evidence, or high suspicion of hepatobiliary malignancy based on imaging, screening laboratory values, and/or clinical symptoms 6. Known history of human immunodeficiency virus (HIV) or positive antibody test at screening 7. Clinically important alcohol consumption, defined as more than 2 drink units per day (equivalent to 20 g) in women and 3 drink units per day (equivalent to 30 g) in men, or inability to quantify alcohol intake reliably 8. History of malignancy diagnosed or treated, actively or within 2 years, or ongoing evaluation for malignancy; localized treatment of squamous or noninvasive basal cell skin cancers and cervical carcinoma in situ is allowed if appropriately treated prior to screening. 9. Treatment with OCA, and fibrates (e.g., bezafibrate, fenofibrate, elafibranor, lanifibranor, pemafibrate, saroglitizar) 6 weeks prior to screening 10. Treatment with colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (>2 weeks) during 2 months prior to screening. See Section 7 for additional medications that may be excluded. 11. Treatment with anti-pruritic drugs (e.g., cholestyramine, naltrexone, rifampicin, sertraline, or any experimental approach) must be on a stable dose within 1 month prior to screening 12. Treatment with any other investigational therapy or device within 30 days or within 5 half-lives, whichever is longer, prior to screening 13. For females, pregnancy or breastfeeding 14. Any ot
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the treatment effect of seladelpar on composite biochemical improvement in cholestasis markers based on ALP and total bilirubin and to evaluate the safety of seladelpar over 12 months of treatment compared to placebo.;Secondary Objective: The key secondary objectives of this study are to evaluate the effect of seladelpar on the normalization of ALP values at 12 months of treatment compared to placebo and to evaluate the effect of seladelpar on pruritus at 6 months of treatment compared to placebo in subjects with baseline moderate to severe pruritus. Other secondary objectives of the study are to evaluate the effect of seladelpar on other measures of cholestasis, metabolic markers, and PBC prognostic criteria; to evaluate the effect of seladelpar on quality of life (QoL); and to evaluate the effect of seladelpar on PBC-associated clinical outcomes.;Primary end point(s): 1. Proportion of subjects who are considered responders at 12 months based on the following composite endpoint of ALP and total bilirubin at 12 months requiring a. ALP <1.67× ULN b. =15% decrease in ALP c. Total bilirubin =1.0× ULN 2. Assessment of TEAEs (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Version 5.0), 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 subjects with ALP =1.0× ULN at 12 months (ie, normalization) 2. Change from baseline in weekly averaged pruritus NRS in subjects with baseline NRS =4 at 6 months;Timepoint(s) of evaluation of this end point: 1. 12 months 2. 6 months | — |
Countries
Argentina, Australia, Austria, Belgium, Canada, Chile, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Mexico, Netherlands, New Zealand, Poland, Romania, Russian Federation, Spain, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactCindy Streicher
CymaBay Therapeutics, Inc.
Outcome results
None listed