Clinical trial NCT03155932: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Primary Biliary Cholangitis
Lead sponsor: Arena Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-05-16
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Change in Serum Alkaline Phosphatase (ALP) Concentration
timeFrame: Baseline, Week 24
measure: Number of Participants With Adverse Events
timeFrame: Up to Week 26
Secondary outcomes:
measure: Change in Serum ALP Concentration
timeFrame: Baseline, Week 12
measure: Pharmacokinetic Parameters of Etrasimod, and Its Metabolites
timeFrame: Up to Week 24
Other outcomes:
measure: Exploratory - Change in Complete Blood Count
timeFrame: Baseline, Week 12, Week 24
measure: Exploratory - Change in Incidence of Fatigue as Assessed by Peripheral Biliary Cholangitis (PBC-40) Scale
timeFrame: Baseline, Week 12, Week 24
measure: Exploratory - Change in Incidence of Pruritus as Assessed by 5-Dimensions (5-D) Itch Scale
timeFrame: Baseline, Week 12, Week 24
measure: Exploratory - Change in Schirmer Test Outcome
timeFrame: Baseline, Week 12, Week 24
measure: Exploratory - Change in Tear Film Break-Up Time
timeFrame: Baseline, Week 12, Week 24
measure: Exploratory - Change in Concentration of Serum High Sensitivity C-Reactive Protein (hsCRP)
timeFrame: Baseline, Week 12, Week 24
measure: Exploratory - Change in Concentration of Serum Alanine Transaminase (ALT)
timeFrame: Baseline, Week 12, Week 24
measure: Exploratory - Change in Concentration of Serum Aspartate Transaminase (AST)
timeFrame: Baseline, Week 12, Week 24
measure: Exploratory - Change in Concentration of Serum Gamma-Glutamyl Transferase (GGT)
timeFrame: Baseline, Week 12, Week 24
measure: Exploratory - Change in Concentration of Serum C4
timeFrame: Baseline, Week 12, Week 24
measure: Exploratory - Change in Concentration of Serum Immunoglobulin
timeFrame: Baseline, Week 12, Week 24
measure: Exploratory - Change in Concentration of Serum GP73
timeFrame: Baseline, Week 12, Week 24
measure: Exploratory - Change in Concentration of Serum Anti-Mitochondrial Antibodies (AMA)
timeFrame: Baseline, Week 12, Week 24
measure: Exploratory - Change in Quality of Life
timeFrame: Baseline, Week 12, Week 24
Locations:
city: Sacramento
country: United States
facility: Gastroenterology and Hepatology, UC Davis Medical Center
state: California
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Texas Liver Institute
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Grafton
country: New Zealand
facility: Auckland City Hospital
state: Auckland
city: Christchurch
country: New Zealand
facility: Christchurch Clinical Studies Trust
Study officials:
affiliation: Arena Pharmaceuticals
name: Arena CT.gov Administrator
role: STUDY_DIRECTOR
References: