Safety, Tolerability, and Efficacy of Etrasimod (APD334) in Participants With Primary Biliary Cholangitis

Phase 2

Terminated

Brief Summary: The purpose of this open-label, pilot, proof of concept study is to evaluate the safety, tolerability, and efficacy of oral etrasimod (APD334) in participants with primary biliary cholangitis (PBC).

Recruitment & Eligibility

Inclusion Criteria

Males or females aged 18 to 80 years (inclusive) at the time of screening, with confirmed Primary Biliary Cholangitis (PBC) diagnosis based upon at least 2 of 3 criteria:
- Anti-mitochondrial antibodies (AMA) titer >1:40 on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies (anti-GP210 and/or anti-SP100)
- Alkaline phosphatase (ALP) >1.5 x upper limit of normal (ULN) for at least 6 months
- Liver biopsy findings consistent with PBC
Use of ursodeoxycholic acid (UDCA) for at least 6 months prior to screening (stable dose for at least 3 months immediately prior to screening)
Participants must have ALP >1.5 x ULN but <10 x ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <5 x ULN, and total bilirubin <ULN, at all screening visits
AST, ALT, ALP, and total bilirubin must have 2 values at least 4 weeks apart that are within 20% of each other

Key

Exclusion Criteria

Chronic liver disease of a non-PBC etiology. However, PBC participants accompanied with primary Sjögren's syndrome (pSS) are eligible to be enrolled.
History or evidence of clinically significant hepatic decompensation
Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease)
Clinically significant infections within 6 weeks prior to treatment start, or infection with hepatitis C virus anytime in the past
Immunosuppressive, immunomodulating, or investigational agents within 30 days prior to treatment start
Treatment with obeticholic acid (OCA) within 30 days prior to Day 1

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Arm && Interventions

Group	Intervention	Description
APD334	APD334	APD334 active treatment for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Change in Serum Alkaline Phosphatase (ALP) Concentration	Baseline, Week 24	Reduction in ALP concentration is a surrogate marker of slower disease progression.
Number of Participants With Adverse Events	Up to Week 26	Safety was assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results.

Secondary Outcome Measures

Name	Time	Method
Change in Serum ALP Concentration	Baseline, Week 12	Reduction in ALP concentration is a surrogate marker of slower disease progression.
Pharmacokinetic Parameters of Etrasimod, and Its Metabolites	Up to Week 24

Locations (9): Gastroenterology and Hepatology, UC Davis Medical Center
🇺🇸
Sacramento, California, United States
Sunshine Coast University Hospital
🇦🇺
Birtinya, Queensland, Australia
Christchurch Clinical Studies Trust
🇳🇿
Christchurch, New Zealand
Auckland City Hospital
🇳🇿
Grafton, Auckland, New Zealand
Texas Liver Institute
🇺🇸
San Antonio, Texas, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
Alfred Health
🇦🇺
Melbourne, Victoria, Australia
Swedish Medical Center
🇺🇸
Seattle, Washington, United States
Royal Prince Alfred Hospital
🇦🇺
Camperdown, New South Wales, Australia