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

Hepatitis B, Chronic Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04365933
• Other study ID #: EYP001-203
• Status: Completed
• Phase: Phase 2
• Start date: May 25, 2020
• Est. completion date: November 29, 2021

Study information

• Verified date: August 2022
• Source: Enyo Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 29, 2021
• Est. primary completion date: June 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• EYP001a
Oral tablets
• Entecavir
Oral tablets
• Pegylated interferon alpha2a
Subcutaneous

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Enyo Pharma

Countries where clinical trial is conducted

Hong Kong,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Treatment-emergent adverse events	Number of Treatment-emergent adverse events including serious adverse events	16 weeks
Primary	Measurement of HBsAg decline	Measurement of HBsAg decline (? log10) from Day 1 to Week 16 of treatment period	16 weeks
Secondary	Measurement of HBsAg decline	Measurement of HBsAg decline (? log10)	40 weeks
Secondary	Measurement of HBV-DNA decline	Measurement of HBV-DNA decline (? log10)	40 weeks
Secondary	Measurement of HBV-pgRNA decline	Measurement of HBV-pgRNA decline (? log10)	40 weeks
Secondary	Measurement of HBcrAg decline	Measurement of HBcrAg decline (? log10)	40 weeks
Secondary	Concentration of EYP001a - Pharmacokinetic	Assessment of fasted plasma concentrations of EYP001a or any active metabolites using a validated liquid chromatography-mass spectrometry	20 weeks
Secondary	Concentration of C4 - Pharmacodynamic biomarker	Assessment of concentrations of plasma C4 (7a hydroxy 4 cholesten 3 one)	40 weeks
Secondary	Concentration of FGF19 - Pharmacodynamic biomarker	Assessment of concentrations of plasma FGF19 over time (Fibroblast Growth Factor 19)	40 weeks
Secondary	Concentration of Bile Acids - Pharmacodynamic biomarker	Assessment of concentrations over time of plasma Bile Acids (chenodeoxycholic acid, deoxycholic acid, lithocholic acid)	40 weeks