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

• ClinicalTrials.gov Identifier: NCT03155932
• Recruitment Status: Terminated
• First Posted: May 16, 2017
• Results First Posted: March 24, 2022
• Last Update Posted: March 24, 2022
• Sponsor: Arena Pharmaceuticals
• Information provided by (Responsible Party): Arena Pharmaceuticals

Tracking Information

• First Submitted Date: May 11, 2017
• First Posted Date: May 16, 2017
• Results First Submitted Date: January 28, 2022
• Results First Posted Date: March 24, 2022
• Last Update Posted Date: March 24, 2022
• Actual Study Start Date: December 29, 2017
• Actual Primary Completion Date: January 31, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 28, 2022)

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

Original Primary Outcome Measures (submitted: May 15, 2017)

• Change from baseline to Week 24 in serum ALP concentration. [ Time Frame: Week 24 ]
  Assess the change in ALP concentration following administration of APD334.
• Number of patients with adverse events and abnormal clinical laboratory tests (including hematology, serum chemistry, coagulation and urinalysis). [ Time Frame: Week 26 ]
  Safety and tolerability of APD334

Current Secondary Outcome Measures (submitted: January 28, 2022)

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

Original Secondary Outcome Measures (submitted: May 15, 2017)

• Change from baseline to Week 12 in serum ALP concentration. [ Time Frame: Week 12 ]
  Assess the change in ALP concentration following administration of APD334.
• Change from baseline to Week 12 and 24 in complete blood counts [ Time Frame: Weeks 12 and 24 ]
• Change from baseline to Week 12 and 24 in quality of life [ Time Frame: Weeks 12 and 24 ]
  measured by the PBC-40 scale
• Change from baseline to Week 12 and 24 in fatigue [ Time Frame: Weeks 12 and 24 ]
  measured by the PBC-40 scale
• Change from baseline to Week 12 and 24 in pruritus [ Time Frame: Weeks 12 and 24 ]
  measured by the 5-D scale
• Change from baseline to Week 12 and 24 in Schirmer test outcome [ Time Frame: Weeks 12 and 24 ]
  Schirmer test in patients with abnormal results at screening
• Change from baseline to Week 12 and 24 in tear film break-up time [ Time Frame: Weeks 12 and 24 ]
  Tear film break-up time in patients with abnormal results at screening
• Change from baseline to Week 12 and 24 in concentration of serum HsCRP [ Time Frame: Weeks 12 and 24 ]
• Change from baseline to Week 12 and 24 in concentration of serum ALT [ Time Frame: Weeks 12 and 24 ]
• Change from baseline to Week 12 and 24 in concentration of serum AST [ Time Frame: Weeks 12 and 24 ]
• Change from baseline to Week 12 and 24 in concentration of serum GGT [ Time Frame: Weeks 12 and 24 ]
• Change from baseline to Week 12 and 24 in concentration of serum C4 [ Time Frame: Weeks 12 and 24 ]
• Change from baseline to Week 12 and 24 in concentration of serum immunoglobulin [ Time Frame: Weeks 12 and 24 ]
• Change from baseline to Week 12 and 24 in concentration of serum GP73 [ Time Frame: Weeks 12 and 24 ]
• Change from baseline to Week 12 and 24 in concentration of serum AMA [ Time Frame: Weeks 12 and 24 ]

Current Other Pre-specified Outcome Measures (submitted: January 28, 2022)

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

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability, and Efficacy of Etrasimod (APD334) in Participants With Primary Biliary Cholangitis
• Official Title: 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Open label

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Primary Biliary Cholangitis

Intervention

Drug: APD334

APD334 active treatment for 24 weeks.

Other Name: etrasimod

Study Arms

Experimental: APD334

APD334 active treatment for 24 weeks.

Intervention: Drug: APD334

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 14, 2019): 2
• Original Estimated Enrollment (submitted: May 15, 2017): 20
• Actual Study Completion Date: January 31, 2019
• Actual Primary Completion Date: January 31, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, New Zealand, United States

Administrative Information

• NCT Number: NCT03155932
• Other Study ID Numbers: APD334-010
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Arena Pharmaceuticals
• Study Sponsor: Arena Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Study Director: Arena CT.gov Administrator; Arena Pharmaceuticals

• PRS Account: Arena Pharmaceuticals
• Verification Date: February 2022