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

ID#: NCT04620733

Age: 18 - 75 years

Gender: All

Healthy Subjects: No

Study Phase: Phase 3

Recruitment Status: Recruiting

Start Date: April 21, 2021

End Date: March 01, 2023

Contact Information:
Elaine Watkins, DO, MSPH
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

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

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. Advanced PBC as defined by the Rotterdam criteria (albumin below the lower limit of normal AND total bilirubin above 1.0× ULN)

2. Clinically important hepatic decompensation, including the history of liver transplantation, current placement on liver transplantation list, or current Model for End-Stage Liver Disease (MELD) score ≥12, complications of portal hypertension and / or cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis, hepatocellular carcinoma, or hepatorenal syndrome

3. History or presence of other concomitant chronic liver diseases (for example, AIH, PSC, NASH, alcoholic liver disease, hepatitis B, hepatitis C, etc.)

4. Known history of human immunodeficiency virus (HIV) or positive antibody test at screening

5. Clinically important alcohol consumption

6. 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.

7. Treatment with obeticholic acid (OCA) or fibrates (eg, bezafibrate, fenofibrate, elafibranor, lanifibranor, pemafibrate, saroglitizar) 3 months prior to screening

8. Treatment with colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (>2 weeks) during 2 months prior to screening

9. Treatment with anti-pruritic drugs (eg, cholestyramine, naltrexone, rifampicin, sertraline, or any experimental approach) must be on a stable dose within 1 month prior to screening

10. Treatment with any other investigational therapy or device within 30 days or within 5 half-lives, whichever is longer, prior to screening

11. For females, pregnancy or breastfeeding

12. 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

13. Immunosuppressant therapies

14. Other medications that effect liver or GI functions