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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03155932

Enrollment

Registered

2017-05-16

Start date

2017-12-29

Completion date

2019-01-31

Last updated

2022-03-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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).

Interventions

DRUGAPD334

APD334 active treatment for 24 weeks.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Open label

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Inclusion 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/

Design outcomes

Primary

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

Secondary

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

Other

Measure	Time frame
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 Complete Blood Count	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
Exploratory - Change in Concentration of Serum C4	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

Countries

Australia, New Zealand, United States

Participant flow

Pre-assignment details

Enrollment was planned for up to 20 participants. Two participants were enrolled into the study and completed 24 weeks of treatment.

Participants by arm

Arm	Count
APD334 Participants received APD334 1 mg tablet once daily (qd) by mouth for 12 weeks. The dose for APD334 was escalated to 2 mg at Week 12 to Week 24, based on the participant's safety and pharmacokinetic (PK) data.	2
Total	2

Baseline characteristics

Characteristic	APD334
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	2 Participants
Race (NIH/OMB) American Indian or Alaska Native	NA Participants
Race (NIH/OMB) Asian	NA Participants
Race (NIH/OMB) Black or African American	NA Participants
Race (NIH/OMB) More than one race	NA Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	NA Participants
Race (NIH/OMB) Unknown or Not Reported	NA Participants
Race (NIH/OMB) White	NA Participants
Sex: Female, Male Female	NA Participants
Sex: Female, Male Male	NA Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 2
other Total, other adverse events	2 / 2
serious Total, serious adverse events	0 / 2

Outcome results

Primary

Change in Serum Alkaline Phosphatase (ALP) Concentration

Reduction in ALP concentration is a surrogate marker of slower disease progression.

Time frame: Baseline, Week 24

Population: Analyses were not conducted due to low enrollment (N=2). In order to protect participant's privacy, the results from the enrolled participants cannot be reported.

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.

Time frame: Up to Week 26

Population: Two participants who were enrolled and received treatment in this study.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
APD334	Number of Participants With Adverse Events	2 Participants

Secondary

Change in Serum ALP Concentration

Reduction in ALP concentration is a surrogate marker of slower disease progression.

Time frame: Baseline, Week 12

Population: Analyses were not conducted due to low enrollment (N=2). In order to protect participant's privacy, the results from the enrolled participants cannot be reported.

Secondary

Pharmacokinetic Parameters of Etrasimod, and Its Metabolites

Time frame: Up to Week 24

Population: Analyses were not conducted due to low enrollment (N=2). In order to protect participant's privacy, the results from the enrolled participants cannot be reported.

Other Pre-specified