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

Conditions: Hepatitis B, Chronic

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).

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.

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: 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.