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

Study Overview
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Brief Summary
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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).

Official Title
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An Open-label, Pilot, Proof of Concept Study to Evaluate the Safety, Tolerability, and Efficacy of Oral Etrasimod (APD334) in Patients With Primary Biliary Cholangitis

Conditions
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Primary Biliary Cholangitis

Intervention / Treatment
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* Drug: APD334


Participation Criteria
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Eligibility Criteria
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Key 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APD334<br>APD334 active treatment for 24 weeks. | Drug: APD334<br>* APD334 active treatment for 24 weeks.<br>* Other names: etrasimod;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum ALP Concentration | Reduction in ALP concentration is a surrogate marker of slower disease progression. | Baseline, Week 12 | 
| Pharmacokinetic Parameters of Etrasimod, and Its Metabolites |  | Up to Week 24 |