Hepatitis B, Chronic
Conditions
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.
Interventions
Sponsors
Enyo Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment-emergent adverse events | 16 weeks | Number of Treatment-emergent adverse events including serious adverse events |
| Measurement of HBsAg decline | 16 weeks | Measurement of HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of EYP001a - Pharmacokinetic | 20 weeks | Assessment of fasted plasma concentrations of EYP001a or any active metabolites using a validated liquid chromatography-mass spectrometry |
| Measurement of HBV-DNA decline | 40 weeks | Measurement of HBV-DNA decline (Δ log10) |
| Concentration of C4 - Pharmacodynamic biomarker | 40 weeks | Assessment of concentrations of plasma C4 (7α hydroxy 4 cholesten 3 one) |
| Measurement of HBsAg decline | 40 weeks | Measurement of HBsAg decline (Δ log10) |
| Concentration of FGF19 - Pharmacodynamic biomarker | 40 weeks | Assessment of concentrations of plasma FGF19 over time (Fibroblast Growth Factor 19) |
| Concentration of Bile Acids - Pharmacodynamic biomarker | 40 weeks | Assessment of concentrations over time of plasma Bile Acids (chenodeoxycholic acid, deoxycholic acid, lithocholic acid) |
| Measurement of HBV-pgRNA decline | 40 weeks | Measurement of HBV-pgRNA decline (Δ log10) |
| Measurement of HBcrAg decline | 40 weeks | Measurement of HBcrAg decline (Δ log10) |
Countries
Hong Kong, South Korea, Taiwan
Outcome results
None listed