A Study of the Oral Farnesoid X Receptor Modulator EYP001a to Assess Its Safety and Anti-viral Effect in Chronic Hepatitis B Patients in Combination With Pegylated Interferon alpha2a Alone and With Entecavir

A Phase 2a Open-label Study of the Oral Farnesoid X Receptor (FXR) Modulator EYP001a to Assess Its Safety and Anti-viral Effect in Chronic Hepatitis B (CHB) Patients in Combination With Pegylated Interferon alpha2a (Peg-IFN) Alone and With Entecavir (ETV)

This is a multi centre, two parallel arm, randomized, open-label, Phase 2a experimental study of oral Farnesoid X Receptor (FXR) modulator EYP001a to assess its safety and anti-viral effect when administered to non-treated (treatment naive or off treatment) chronic Hepatitis B (CHB) patients in combination with entecavir (ETV) and pegylated interferon alpha2a (peg-IFN). An experimental treatment period of 16 weeks will be followed by a 24 week maintenance period with ETV standard of care (SoC).

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: EYP001a; Drug: Entecavir; Drug: Pegylated interferon alpha2a

Detailed Description

In total 30 eligible patients will be enrolled and randomized at approximately 7 study sites.

Patients will be randomized prior to study drug (EYP001a, ETV and peg-IFN) administration on Day 1 in the ratio of 1:1 into 2 treatment arms:

• Arm 1: EYP001a QD + ETV 0.5 mg QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW (± 3 days) (15 patients)
• Arm 2: EYP001a QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW (± 3 days) (15 patients)

Patients enrolled in the study will be assessed as outpatients. Patient screening will occur no more than 37 days prior to the Day 1 visit. Eligible patients will undergo further assessments on Day 1 to qualify for study drug administration on Day 1.

The visits during the study are planned as below:

• Screening visit: 5 weeks (37 days)
• 16 weeks treatment period
• 24 weeks maintenance period. During maintenance period patients are kept on ETV until the end of the trial at Week 40.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • ENYO PHARMA Investigative site HK01
• Korea, Republic of
  • Busan, Korea, Republic of
    • ENYO PHARMA Investigative site KR01
• Taiwan
  • Kaohsiung, Taiwan
    • ENYO PHARMA Investigative site TW03
  • Kaohsiung, Taiwan
    • ENYO PHARMA Investigative site TW04
  • Taipei, Taiwan
    • ENYO PHARMA Investigative site TW01
  • Taoyuan, Taiwan
    • ENYO PHARMA Investigative site TW02

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has given voluntary written informed consent before performance of any study related procedure.
• Are treatment naive or without HBV treatment for at least 60 days or 5 times the elimination half-life, whichever is longer.

• Patient has CHB:

  1. HBV DNA ≥ 20,000 IU/mL for HBeAg positive and ≥2'000 for HBeAg negative and
  2. HBsAg ≥ 2.5 log10 IU/mL.
• Has liver imaging to screen for hepatocellular carcinoma or concomitant pancreaticobiliary disease either in the prior 6 months or at screening.
• Patient is not of childbearing potential or, if of childbearing potential, is not pregnant as confirmed by a negative serum human chorionic gonadotropin test at screening and is not planning a pregnancy during the course of the study.

Exclusion Criteria:

• Is an employee of a clinical research organization, vendor, or Sponsor involved with this study.
• Has known hepatocellular carcinoma or pancreaticobiliary disease.
• Neutropenia (defined by two confirmed values during Screening period of < 1500/μL).
• Has Gilbert syndrome.
• Shows evidence of worsening liver tests, defined as either a confirmed (2 assessments at least 3 days apart) increase > 2 ULN ALT or AST or an increase of > 1.5 × baseline value of TBL or associated with clinical signs or symptoms of liver impairment.
• Has known or suspected non-CHB liver disease
• History of cirrhosis or liver decompensation, including ascites, hepatic encephalopathy, or presence of oesophageal varices.
• Probable or possible F4 stage with a vibration controlled transient elastography (VCTE) > 11.7 kPa leads to exclusion
• Has known history of alcohol abuse or daily heavy alcohol consumption

• Has any of the following exclusionary laboratory results at screening:

  1. ALT > 2 × ULN, AST > 2 × ULN
  2. INR > 1.2 × ULN, (normal range is 0.8 to 1.2)
  3. Platelet count < 100 G/L
  4. Estimated glomerular filtration rate < 50 mL/min/1.73m2 (the Modification of Diet in Renal Disease formula)
  5. Thyroid-stimulating hormone > 1.5 × ULN or abnormal free triiodothyronine or free thyroxine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; EYP001a Dose A QD + ETV 0.5 mg QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW	Drug: EYP001a; Oral tablets; Drug: Entecavir; Oral tablets; Drug: Pegylated interferon alpha2a; Subcutaneous
Experimental: Arm 2; EYP001a Dose A QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW	Drug: EYP001a; Oral tablets; Drug: Pegylated interferon alpha2a; Subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment-emergent adverse events	Number of Treatment-emergent adverse events including serious adverse events	16 weeks
Measurement of HBsAg decline	Measurement of HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment period	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of HBsAg decline	Measurement of HBsAg decline (Δ log10)	40 weeks
Measurement of HBV-DNA decline	Measurement of HBV-DNA decline (Δ log10)	40 weeks
Measurement of HBV-pgRNA decline	Measurement of HBV-pgRNA decline (Δ log10)	40 weeks
Measurement of HBcrAg decline	Measurement of HBcrAg decline (Δ log10)	40 weeks
Concentration of EYP001a - Pharmacokinetic	Assessment of fasted plasma concentrations of EYP001a or any active metabolites using a validated liquid chromatography-mass spectrometry	20 weeks
Concentration of C4 - Pharmacodynamic biomarker	Assessment of concentrations of plasma C4 (7α hydroxy 4 cholesten 3 one)	40 weeks
Concentration of FGF19 - Pharmacodynamic biomarker	Assessment of concentrations of plasma FGF19 over time (Fibroblast Growth Factor 19)	40 weeks
Concentration of Bile Acids - Pharmacodynamic biomarker	Assessment of concentrations over time of plasma Bile Acids (chenodeoxycholic acid, deoxycholic acid, lithocholic acid)	40 weeks

Collaborators and Investigators

• Sponsor: Enyo Pharma

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2020
• Primary Completion (Actual): June 16, 2021
• Study Completion (Actual): November 29, 2021

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: April 27, 2020
• First Posted (Actual): April 28, 2020

Study Record Updates

• Last Update Posted (Actual): August 25, 2022
• Last Update Submitted That Met QC Criteria: August 22, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Peginterferon alfa-2a; Interferon alpha-2; Entecavir
• Other Study ID Numbers: EYP001-203

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No