Chronic Hepatitis B MedDRA version: 20.1 Level: PT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: EYP001a
Product Code: EYP001a
Pharmaceutical Form: Tablet
CAS Number: 1192171-69-9
Current Sponsor code: EYP001a
Sponsors
ENYO Pharma SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has given voluntary written informed consent before performance of any study related procedure. 2. Must be 18 to 65 years of age, inclusive 3. Are on stable NA therapy for at least 12 months from the screening date (ETV or TDF) 4. Has virally suppressed CHB: a. HBV DNA 100 IU/mL 5. Has liver imaging to screen for hepatocellular carcinoma or concomitant pancreaticobiliary disease either in the prior 6 months or at screening. 6. Has liver tests during the Screening Period defined as follows: a. The baseline values (i.e. two measurements at least 3 days apart: one can be from medical history if not older than 12 months and one during screening period) with both measurements of ALT or AST are = 2 × ULN b. Normal or clinically not relevant levels of ALP (= 1.5 ULN) c. Has total bilirubin (TBL) = 22.2 µmol/L, which corresponds to = 1.3 mg/dL. d. Has conjugated (direct) bilirubin of = 0.3 mg/dL (i.e. 5.1 µmol/L) e. Has normal or clinically not relevant levels of GGT (= 2.0 ULN) f. International normalized ratio = 1.2 x ULN, unless on anticoagulant therapy g. Platelet count = 100 G/L h. Has albumin =3.5 g/dL. 7. 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. 8. Women of childbearing potential (WOCBP) and male patients with WOCBP partners must agree to use a dual method of contraception as defined in the study protocol or practice complete abstinence from sexual intercourse if this is the patient’s usual and preferred lifestyle throughout the duration of the study and for 90 days after stopping study drug. Patients who are using hormonal contraceptives should be instructed to use an additional contraceptive measure during the study. Note: A woman is considered of childbearing potential following menarche and until becoming postmenopausal unless permanently sterile. A postmenopausal state is defined as no menses for >12 consecutive months without an alternative medical cause. A follicle stimulating hormone level in the postmenopausal range will be used to confirm a postmenopausal state in women =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Is an employee of a CRO, vendor, or Sponsor involved with this study 2. Has known hepatocellular carcinoma or pancreaticobiliary disease 3. Neutropenia (defined by two confirmed values within screening period of 2 ULN ALT or AST or an increase of >1.5 × first assessed value of TBL or associated with clinical signs or symptoms of liver impairment. 6. Has known or suspected non CHB liver disease, including, but not limited to, Hepatitis D virus co-infection, alcoholic liver disease, non alcoholic steatohepatitis diagnosed with liver biopsy, autoimmune disease, HIV, active hepatitis C virus (HCV ), Wilson disease, hemochromatosis, hepatocellular carcinoma (normal AFP at screening required) or suspected or known other liver cancer, primary biliary cholangitis, primary sclerosing cholangitis, drug induced liver injury (DILI), bile duct obstruction. 7. History of cirrhosis or liver decompensation, including ascites, hepatic encephalopathy, or presence of oesophageal varices 8. Probable or possible F3 stage with a vibration controlled transient elastography (VCTE). Patients with normal baseline ALT and VCTE >8.8 kPa are excluded. Patients with baseline ALT >ULN (but 10.5 kPa at baseline are excluded 9. Has known history of alcohol abuse or daily heavy alcohol consumption (females: >14 units of alcohol per week; males: >21 units of alcohol per week [1 unit of alcohol is equivalent to a half pint of beer {285 mL}, 1 measure of spirits {25 mL}, or 1 glass of wine {125 mL}]). Has an AUDIT C score of >3 points for men and women AND a full AUDIT score of >8 points at screening. 10. Is pregnant or breastfeeding 11. Has clinically relevant immunosuppression, including, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia. 12. Has a known pre existing medical or psychiatric condition that could interfere with the patient’s ability to provide informed consent or participate in study conduct, or that may confound study findings. 13. Has known dyslipidaemia with higher cardio-vascular risk from worsening lipid parameters (history of clinically significant cardiovascular or cerebrovascular disease during 12 months prior to study entry). 14. Has, in the opinion of the Investigator, clinically significant cardiovascular or cerebrovascular disease within 12 months prior to the first study drug administration, including, but not limited to, myocardial infarction, acute coronary syndrome, revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or ischemic stroke, or implanted defibrillator or pacemaker 15. Has participated in any study with administration of an investigational drug in the past 30 days, or 5 half lives, whichever is longer, prior to the first study drug administration in the current study 16. Has had major visceral or orthopaedic surgery within 30 days prior to the first study drug administration in the current study 17. Has a hypersensitivity to the study drug or to any of the excipients or placebo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effect of EYP001a on top of NA (SOC therapy) on HBsAg plasma levels; Secondary Objective: • To establish the effect of EYP001a on top of NA on HBsAg responder rate at the end of the 16-week EYP001a treatment and at 24-week of follow-up (Week 40). • To establish the effect of EYP001a on top of NA on HBsAg loss rate at the end of the 16-week EYP001a treatment and at 24-week of follow-up (Week 40). • To stablish the HBV virologic failure rate (breakthrough) during the 24-weeks follow-up period after stopping EYP001a with ongoing NA. • To determine HBV viral response, HBV pgRNA, HBcrAg and HbeAg, anti-HBe and anti-HBs at the end of the 16-week EYP001a treatment and Week 40 of follow-up. • To explore the safety profile of EYP001a treatment in combination with NA. • To determine the plasma concentration of EYP001a and PD markers (plasma C4 (7a-hydroxy-4-cholesten-3-one)), FGF19 and BAs. ;Primary end point(s): Efficacy assessed as HBsAg decline (? log10) from Day 1 to Week 16 of treatment;Timepoint(s) of evaluation of this end point: From Day 1 to Week 16 of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Throughout the Study; Secondary end point(s): • Efficacy assessed as: o HBsAg responder rate (decrease from baseline = 1.0 on the log10 scale) at Week 16 of treatment and Weeks 20, 28 and 40 of follow up. o HBsAg responder rate (decrease from baseline = 0.5 on the log10 scale) at Weeks 12 and 16 of treatment and Weeks 20, 28 and 40 of follow up. o HBsAg loss rate (% patients with HBsAg LLOQ) at Week 16 of treatment period and Weeks 20, 28 and 40 during follow-up period o Virologic failure rate (breakthrough) of HBV-DNA (% patients with a confirmed quantifiable HBV DNA increase of = 1log10 HBV DNA copies/mL above LLOQ) assessed at Week 16 of treatment period and Weeks 20, 28 and 40 during follow-up period o HBV-pgRNA decline (? log10) from Day 1 to Weeks 4, 8, 12, 16 of treatment period and Week 40 of maintenance period o HBcrAg decline (? log10) from Day 1 to Weeks 4, 8, 12, 16 of treatment period and Week 40 of maintenance period o HBeAg quantification for HBeAg pos patients and changes at Week 16 of treatment and Week 40 of follow-up o Fibroscan VCTE change from screening value to Weeks 16 and 40 or ET value • Safety and Tolerability assessed as: o Treatment-emergent adverse events (TEAEs) (including SAEs) o All-cause mortality o Clinical laboratory tests o Pruritus assessment o Vital signs (blood pressure, heart rate, respiratory rate, and temperature) o Concomitant medications o Physical examinations o 12-lead ECG • PK assessed as: o Plasma concentration of EYP001a or any relevant active metabolites (as identified in an ongoing phase 1 study) | — |
Countries
Australia, Korea, Republic of, Poland
Contacts
Public ContactPietro Scalfaro
ENYO Pharma SA
Outcome results
None listed