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

Primary Biliary Cholangitis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03155932
• Other study ID #: APD334-010
• Status: Terminated
• Phase: Phase 2
• Start date: December 29, 2017
• Est. completion date: January 31, 2019

Study information

• Verified date: February 2022
• Source: Arena Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: January 31, 2019
• Est. primary completion date: January 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cholangitis
• Liver Cirrhosis, Biliary
• Primary Biliary Cholangitis

Intervention

Drug:
• APD334
APD334 active treatment for 24 weeks.

Locations

Country	Name	City	State
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Alfred Health	Melbourne	Victoria
New Zealand	Christchurch Clinical Studies Trust	Christchurch
New Zealand	Auckland City Hospital	Grafton	Auckland
United States	Baylor College of Medicine	Houston	Texas
United States	Gastroenterology and Hepatology, UC Davis Medical Center	Sacramento	California
United States	Texas Liver Institute	San Antonio	Texas
United States	Swedish Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Arena Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory - Change in Complete Blood Count		Baseline, Week 12, Week 24
Other	Exploratory - Change in Incidence of Fatigue as Assessed by Peripheral Biliary Cholangitis (PBC-40) Scale		Baseline, Week 12, Week 24
Other	Exploratory - Change in Incidence of Pruritus as Assessed by 5-Dimensions (5-D) Itch Scale		Baseline, Week 12, Week 24
Other	Exploratory - Change in Schirmer Test Outcome		Baseline, Week 12, Week 24
Other	Exploratory - Change in Tear Film Break-Up Time		Baseline, Week 12, Week 24
Other	Exploratory - Change in Concentration of Serum High Sensitivity C-Reactive Protein (hsCRP)		Baseline, Week 12, Week 24
Other	Exploratory - Change in Concentration of Serum Alanine Transaminase (ALT)		Baseline, Week 12, Week 24
Other	Exploratory - Change in Concentration of Serum Aspartate Transaminase (AST)		Baseline, Week 12, Week 24
Other	Exploratory - Change in Concentration of Serum Gamma-Glutamyl Transferase (GGT)		Baseline, Week 12, Week 24
Other	Exploratory - Change in Concentration of Serum C4		Baseline, Week 12, Week 24
Other	Exploratory - Change in Concentration of Serum Immunoglobulin		Baseline, Week 12, Week 24
Other	Exploratory - Change in Concentration of Serum GP73		Baseline, Week 12, Week 24
Other	Exploratory - Change in Concentration of Serum Anti-Mitochondrial Antibodies (AMA)		Baseline, Week 12, Week 24
Other	Exploratory - Change in Quality of Life		Baseline, Week 12, Week 24
Primary	Change in Serum Alkaline Phosphatase (ALP) Concentration	Reduction in ALP concentration is a surrogate marker of slower disease progression.	Baseline, Week 24
Primary	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	Change in Serum ALP Concentration	Reduction in ALP concentration is a surrogate marker of slower disease progression.	Baseline, Week 12
Secondary	Pharmacokinetic Parameters of Etrasimod, and Its Metabolites		Up to Week 24