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

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

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).

Study Overview

• Status: Terminated
• Conditions: Primary Biliary Cholangitis
• Intervention / Treatment: Drug: APD334

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Sunshine Coast University Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health
• New Zealand
  • Christchurch, New Zealand, 8011
    • Christchurch Clinical Studies Trust
  • Auckland
    • Grafton, Auckland, New Zealand, 1023
      • Auckland City Hospital
• United States
  • California
    • Sacramento, California, United States, 95817
      • Gastroenterology and Hepatology, UC Davis Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78215
      • Texas Liver Institute
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APD334; APD334 active treatment for 24 weeks.	Drug: APD334; APD334 active treatment for 24 weeks.; Other Names: etrasimod

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Time Frame
Exploratory - Change in Complete Blood Count	Baseline, Week 12, Week 24
Exploratory - Change in Incidence of Fatigue as Assessed by Peripheral Biliary Cholangitis (PBC-40) Scale	Baseline, Week 12, Week 24
Exploratory - Change in Incidence of Pruritus as Assessed by 5-Dimensions (5-D) Itch Scale	Baseline, Week 12, Week 24
Exploratory - Change in Schirmer Test Outcome	Baseline, Week 12, Week 24
Exploratory - Change in Tear Film Break-Up Time	Baseline, Week 12, Week 24
Exploratory - Change in Concentration of Serum High Sensitivity C-Reactive Protein (hsCRP)	Baseline, Week 12, Week 24
Exploratory - Change in Concentration of Serum Alanine Transaminase (ALT)	Baseline, Week 12, Week 24
Exploratory - Change in Concentration of Serum Aspartate Transaminase (AST)	Baseline, Week 12, Week 24
Exploratory - Change in Concentration of Serum Gamma-Glutamyl Transferase (GGT)	Baseline, Week 12, Week 24
Exploratory - Change in Concentration of Serum C4	Baseline, Week 12, Week 24
Exploratory - Change in Concentration of Serum Immunoglobulin	Baseline, Week 12, Week 24
Exploratory - Change in Concentration of Serum GP73	Baseline, Week 12, Week 24
Exploratory - Change in Concentration of Serum Anti-Mitochondrial Antibodies (AMA)	Baseline, Week 12, Week 24
Exploratory - Change in Quality of Life	Baseline, Week 12, Week 24

Collaborators and Investigators

• Sponsor: Arena Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2017
• Primary Completion (Actual): January 31, 2019
• Study Completion (Actual): January 31, 2019

Study Registration Dates

• First Submitted: May 11, 2017
• First Submitted That Met QC Criteria: May 15, 2017
• First Posted (Actual): May 16, 2017

Study Record Updates

• Last Update Posted (Actual): March 24, 2022
• Last Update Submitted That Met QC Criteria: February 28, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Cholangitis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: APD334-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No