Back to resultsA 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
Primary Purpose
Hepatitis B, Chronic
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
EYP001a
Entecavir
Pegylated interferon alpha2a
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis B, Chronic
Eligibility Criteria
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:
- HBV DNA ≥ 20,000 IU/mL for HBeAg positive and ≥2'000 for HBeAg negative and
- 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:
- ALT > 2 × ULN, AST > 2 × ULN
- INR > 1.2 × ULN, (normal range is 0.8 to 1.2)
- Platelet count < 100 G/L
- Estimated glomerular filtration rate < 50 mL/min/1.73m2 (the Modification of Diet in Renal Disease formula)
- Thyroid-stimulating hormone > 1.5 × ULN or abnormal free triiodothyronine or free thyroxine.
Sites / Locations
- ENYO PHARMA Investigative site HK01
- ENYO PHARMA Investigative site KR01
- ENYO PHARMA Investigative site TW03
- ENYO PHARMA Investigative site TW04
- ENYO PHARMA Investigative site TW01
- ENYO PHARMA Investigative site TW02
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm 1
Arm 2
Arm Description
EYP001a Dose A QD + ETV 0.5 mg QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW
EYP001a Dose A QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW
Outcomes
Primary Outcome Measures
Number of Treatment-emergent adverse events
Number of Treatment-emergent adverse events including serious adverse events
Measurement of HBsAg decline
Measurement of HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment period
Secondary Outcome Measures
Measurement of HBsAg decline
Measurement of HBsAg decline (Δ log10)
Measurement of HBV-DNA decline
Measurement of HBV-DNA decline (Δ log10)
Measurement of HBV-pgRNA decline
Measurement of HBV-pgRNA decline (Δ log10)
Measurement of HBcrAg decline
Measurement of HBcrAg decline (Δ log10)
Concentration of EYP001a - Pharmacokinetic
Assessment of fasted plasma concentrations of EYP001a or any active metabolites using a validated liquid chromatography-mass spectrometry
Concentration of C4 - Pharmacodynamic biomarker
Assessment of concentrations of plasma C4 (7α hydroxy 4 cholesten 3 one)
Concentration of FGF19 - Pharmacodynamic biomarker
Assessment of concentrations of plasma FGF19 over time (Fibroblast Growth Factor 19)
Concentration of Bile Acids - Pharmacodynamic biomarker
Assessment of concentrations over time of plasma Bile Acids (chenodeoxycholic acid, deoxycholic acid, lithocholic acid)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04365933
Brief Title
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
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)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
May 25, 2020 (Actual)
Primary Completion Date
June 16, 2021 (Actual)
Study Completion Date
November 29, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Enyo Pharma
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1
Arm Type
Experimental
Arm Description
EYP001a Dose A QD + ETV 0.5 mg QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW
Arm Title
Arm 2
Arm Type
Experimental
Arm Description
EYP001a Dose A QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW
Intervention Type
Drug
Intervention Name(s)
EYP001a
Intervention Description
Oral tablets
Intervention Type
Drug
Intervention Name(s)
Entecavir
Intervention Description
Oral tablets
Intervention Type
Drug
Intervention Name(s)
Pegylated interferon alpha2a
Intervention Description
Subcutaneous
Primary Outcome Measure Information:
Title
Number of Treatment-emergent adverse events
Description
Number of Treatment-emergent adverse events including serious adverse events
Time Frame
16 weeks
Title
Measurement of HBsAg decline
Description
Measurement of HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment period
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
Measurement of HBsAg decline
Description
Measurement of HBsAg decline (Δ log10)
Time Frame
40 weeks
Title
Measurement of HBV-DNA decline
Description
Measurement of HBV-DNA decline (Δ log10)
Time Frame
40 weeks
Title
Measurement of HBV-pgRNA decline
Description
Measurement of HBV-pgRNA decline (Δ log10)
Time Frame
40 weeks
Title
Measurement of HBcrAg decline
Description
Measurement of HBcrAg decline (Δ log10)
Time Frame
40 weeks
Title
Concentration of EYP001a - Pharmacokinetic
Description
Assessment of fasted plasma concentrations of EYP001a or any active metabolites using a validated liquid chromatography-mass spectrometry
Time Frame
20 weeks
Title
Concentration of C4 - Pharmacodynamic biomarker
Description
Assessment of concentrations of plasma C4 (7α hydroxy 4 cholesten 3 one)
Time Frame
40 weeks
Title
Concentration of FGF19 - Pharmacodynamic biomarker
Description
Assessment of concentrations of plasma FGF19 over time (Fibroblast Growth Factor 19)
Time Frame
40 weeks
Title
Concentration of Bile Acids - Pharmacodynamic biomarker
Description
Assessment of concentrations over time of plasma Bile Acids (chenodeoxycholic acid, deoxycholic acid, lithocholic acid)
Time Frame
40 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
HBV DNA ≥ 20,000 IU/mL for HBeAg positive and ≥2'000 for HBeAg negative and
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:
ALT > 2 × ULN, AST > 2 × ULN
INR > 1.2 × ULN, (normal range is 0.8 to 1.2)
Platelet count < 100 G/L
Estimated glomerular filtration rate < 50 mL/min/1.73m2 (the Modification of Diet in Renal Disease formula)
Thyroid-stimulating hormone > 1.5 × ULN or abnormal free triiodothyronine or free thyroxine.
Facility Information:
Facility Name
ENYO PHARMA Investigative site HK01
City
Hong Kong
Country
Hong Kong
Facility Name
ENYO PHARMA Investigative site KR01
City
Busan
Country
Korea, Republic of
Facility Name
ENYO PHARMA Investigative site TW03
City
Kaohsiung
Country
Taiwan
Facility Name
ENYO PHARMA Investigative site TW04
City
Kaohsiung
Country
Taiwan
Facility Name
ENYO PHARMA Investigative site TW01
City
Taipei
Country
Taiwan
Facility Name
ENYO PHARMA Investigative site TW02
City
Taoyuan
Country
Taiwan
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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
We'll reach out to this number within 24 hrs