Hepatitis B Chronic HBV
Conditions
Interventions
The study will consist of Part A and Part B. Subjects who have completed Part A
and new CHBV subjects who meet study entry criteria are eligible for Part B.
Part A:
The subjects will be randomly as
n=6)
* Treatment B: oral EYP001a (1x200 mg/day
n=6)
* Treatment C: oral EYP001a (1x400 mg/day
n=6)
* Treatment D: oral EYP001a (2x200 mg/day
n=6)
* Treatment E: oral placebo (n=6) or
* Treatment F: oral ETV (open-label 0.5 mg/day) (n=6)
An external, independent Data Safety Monitoring Committee (DSMC) will review
all available unblinded p
Chronical
FXR-agonist
Sponsors
Enyo Pharma, SA
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Have given voluntary written informed consent; 2. Have documented medical history of chronic HBV infection (defined as HBsAg positivity lasting for at least 6 months at whatever point in time) and have recent, documented, laboratory tests at the screening visit with the following results: * Documented positive hepatitis B surface antigen (HBsAg) and * Documented HBV DNA > 1000 IU/mL (HBV DNA load values of 750-1000 IU/mL may be allowed following consultation with the sponsor. Subjects with recent (within 12 months) documented HBV DNA >1000 IU/mL but with HBV DNA values below 750 at screening can be discussed with sponsor for inclusion); Note: subject can be either hepatitis Be antigen (HBeAg) negative or positive, this test result is not required for randomization and if not available can be established during the Day 1 visit with baseline PD virology assessments. 3. Is anti-HBV treatment naive or treatment experienced (see also exclusion criterion #3). 4. Gender: male or female. 5. Age: 18 to 65 years inclusive. 6. Body mass index (BMI): 17.0-35.0 kg/m2 inclusive. 7. Has clinical chemistry, hematology, coagulation and urinalysis tests within normal, allowable limits (with the exception of alanine aminotransferase [ALT]); see inclusion criterion #10); if there is an out of range value, the result must be considered clinically non-significant by the investigator in order to be eligible. 8. Vital signs after at least 5 minutes resting in supine position at screening within the following ranges: * systolic blood pressure: between 90 mm Hg and 145 mm Hg * diastolic blood pressure: between 45 mm Hg and 90 mm Hg * heart rate: between 40 bpm and 100 bpm 9. Have no clinically significant abnormal 12-lead automatic electrocardiogram (ECG) (incomplete right bundle branch block can be accepted) at screening: PR interval * 210 ms, QRS-duration < 120 ms, QTc-interval (Fridericia*s) * 450 msec. 10. ALT at screening * 5 x upper limit of normal (ULN). 11. Agrees to abstain from all medication, including non-prescription and prescription medication for 28 days prior to the Day 1 study visit, except for authorized medications (such as hormonal contraceptives for females, vitamins prescribed per label dosages and paracetamol). On a case-by-case basis, regular co-medication either as defined on the medication exception list or as documented by written approval from the sponsor as acceptable prior to randomization, will not be considered as a deviation from this criterion. 12. At screening, females must be non-pregnant and non-lactating, or of non-childbearing potential (documented tubal ligation, bilateral oophorectomy or hysterectomy or physiologically incapable of becoming pregnant, or at least 1 year post-menopausal [amenorrhea duration of 12 consecutive months); non pregnancy will be confirmed for all females of child bearing potential by a pregnancy test conducted at screening, during the treatment period and at the EOS/ET visit. 13. Female subjects of child-bearing potential, with a fertile male sexual partner, should be willing to use adequate contraception from screening until 90 days after the EOS/ET visit. Adequate contraception is defined as using hormonal contraceptives or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm or cervical cap, or a condom. Als
Exclusion criteria
Exclusion criteria: 1. Employee of a CRO participating in this study or the sponsor. 2. Has certain or probable compensated liver cirrhosis documented by at least 2 of the following: a. Optional assessment: has documented liver histology Metavir score (F4), Ishak >5 or Scheuer (F4) b. Mandatory assessment: has presence or history of ascites, spontaneous bacterial peritonitis, esophageal varices, hepatic encephalopathy c. Mandatory assessment: platelet count below 90,000/uL within 12 months of screening visit d. Optional assessment: positive indirect blood test of APRI or FIB4 or positive direct blood test Fibrosure, Fibrotest, or FibroSpect within 12 months of screening visit e. Optional assessment: has positive elastography within 6 months of screening visit (Fibroscan or Shearwave Aixplorer) f. Optional assessment: has abnormal liver imaging (CT/US/MRI) consistent with a lobular/nodular liver and cirrhosis or indirect signs of portal hypertension. 3. Subject is HBV treatment experienced AND currently on anti-HBV treatment during the 30 days (or 5 half-lives of the considered anti-HBV drug, whichever is longer) before the first investigational product administration and until the last study visit. 4. Co-infection with active hepatitis C virus (HCV, except for patients with sustained viral response SVR, who can be included). 5. Co-infection with human immunodeficiency virus (HIV). Note: hepatitis D virus (HDV) status is not required for randomization and if not available can be established during the Day 1 visit with baseline PD virology assessments. 6. Receives or plans to receive systemic immunosuppressive or immunomodulating medications (e.g. IFN) during the study or * 4 months prior to the first investigational product administration. 7. Has clinically relevant immunosuppression from, but not limited to immunodeficiency conditions such as common variable hypogammaglobulinemia. 8. Clinical diagnosis of substance abuse during * 12 months prior to screening with narcotics or cocaine or with alcohol (regular consumption > 21 units/week [men] and > 14 units/week [women]; 1 unit = 1*2 pint of beer, 25 mL shot of 40% spirit or a 125 mL glass of wine. Expressed in g/day: > 30 g/day [men] and > 20 g/day [women]). 9. Has a positive drug urine screen (cocaine, phencyclidine, amphetamines (incl. methamphetamines), opiates (incl. heroin, codeine and morphine), benzodiazepines, barbiturates, methadone or alcohol screen. Subjects who admit the occasional use of cannabis will not be excluded as long as they are able to abstain from cannabis when they are assessed at study visits. 10. Has any known pre-existing medical or psychiatric condition that could interfere with the subject*s ability to provide informed consent or participate in study conduct, or that may confound study findings. 11. Has been diagnosed with hepatocellular carcinoma (HCC). 12. Has a history of long QT syndrome. 13. Has a history of clinically significant gastrointestinal disease, especially peptic ulcerations, gastrointestinal bleeding, ulcerative colitis, Crohn*s disease or Inflammatory Bowel Syndrome, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, or cardiovascular disease or any other condition which, in the opinion of the investigator, would jeopardize the safety of the subject or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety endpoint: evaluations will include the following: * Incidence and severity of AEs; * Vital signs parameters; * Physical examination findings; * ECG parameters; * Clinical laboratory parameters (serum chemistry, hematology, coagulation, urinalysis). Pharmacokinetic endpoints:EYP001a PK parameters to be calculated include: * Maximum concentration (Cmax); * Time to maximum concentration (Tmax); * Area under the concentration-time curve from time 0 to last measurable concentration (AUC0-6h); * Lag time (tlag); * Average plasma drug concentration at steady state (Cavg,ss); * Time to steady state (Tss). | — |
Secondary
| Measure | Time frame |
|---|---|
| PD markers: The following markers will be measured: -Bile acids: Bile acid precursor C4 (7*hydroxy-4-cholesten-3-one) and fibroblast growth factor 19 (FGF19) -Lipid metabolism: Total plasma cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein (Apo) A1 and ApoB. -HBV virology: hepatitis B surface antigen (HBsAg), HBV core-related antigen (HBcrAg), hepatitis B envelope antigen (HBeAg), HBV DNA (viral load) and HBV pgRNA. | — |
Countries
Australia, Netherlands, Poland, Thailand
Outcome results
None listed