Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
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
Phase
Phase 3
Funding Agency/Sponsor
Industry
Disease
PBC (Primary Biliary Cholangitis)
Enrollment Eligibility
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 definitive diagnosis of 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:
1. ALP ≥1.67× ULN
2. Aspartate aminotransferase (AST) ≤3× ULN
3. ALT ≤3× ULN
4. Total bilirubin ≤2× ULN
5. Estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 (calculated by the
Modification of Diet in Renal Disease study equation)
6. 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.
7. 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 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
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:
1. 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.
2. Complications of portal hypertension, including known esophageal varices, history
of variceal bleeds or related interventions (ege.g., transjugular intrahepatic
portosystemic shunt placement), ascites, and hepatic encephalopathy.
3. Cirrhosis with complications, including history or presence of spontaneous
bacterial peritonitis, hepatocellular carcinoma, or hepatorenal syndrome.
5. Other chronic liver diseases:
1. Current features of AIH as determined by the investigator based on
immunoserology, liver biochemistry, or historic confirmed liver histology.
2. PSC determined by the presence of diagnostic cholangiographic findings.
3. History or clinical evidence of alcoholic liver disease.
4. History or clinical evidence of alpha-1-antitrypsin deficiency.
5. History of biopsy confirmed NASH.
6. History or evidence of Gilbert's syndrome with elevated total bilirubin.
7. History or evidence of hemochromatosis.
8. Hepatitis B, defined as the presence of hepatitis B surface antigen.
9. Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid.
10. 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 obeticholic acid (OCA) or 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
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 other condition(s) that would compromise the safety of the subject or compromise
the quality of the clinical study, as judged by the investigator
15. Immunosuppressant therapies
16. 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.
17. Active COVID-19 infection during Screening.