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


Trial ID: NCT04620733


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

Official Title

RESPONSE: A Placebo-controlled, Randomized, Phase 3 Study to Evaluate the Efficacy and Safety of Seladelpar in Patients With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA)

Stanford Investigator(s)

Aparna Goel

Clinical Associate Professor, Medicine - Gastroenterology & Hepatology


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

   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.


drug: Seladelpar 10 mg

drug: Placebo

drug: Seladelpar 5 mg


Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305