A randomized, double-blind, placebo-controlled study to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of the FXR-agonist EYP001a in chronically HBV infected<br>subjects.
- Conditions
- Hepatitis BChronic HBV10019654
- Registration Number
- NL-OMON46529
- Lead Sponsor
- Enyo Pharma, SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 18
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Safety endpoint: evaluations will include the following:<br /><br>* Incidence and severity of AEs;<br /><br>* Vital signs parameters;<br /><br>* Physical examination findings;<br /><br>* ECG parameters;<br /><br>* Clinical laboratory parameters (serum chemistry, hematology, coagulation,<br /><br>urinalysis).<br /><br><br /><br>Pharmacokinetic endpoints:EYP001a PK parameters to be calculated include:<br /><br>* Maximum concentration (Cmax);<br /><br>* Time to maximum concentration (Tmax);<br /><br>* Area under the concentration-time curve from time 0 to last measurable<br /><br>concentration (AUC0-6h);<br /><br>* Lag time (tlag);<br /><br>* Average plasma drug concentration at steady state (Cavg,ss);<br /><br>* Time to steady state (Tss).</p><br>
- Secondary Outcome Measures
Name Time Method <p>PD markers:<br /><br><br /><br>The following markers will be measured:<br /><br><br /><br>-Bile acids: Bile acid precursor C4 (7*hydroxy-4-cholesten-3-one) and<br /><br>fibroblast growth factor 19 (FGF19)<br /><br><br /><br>-Lipid metabolism: Total plasma cholesterol, triglycerides, high density<br /><br>lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol,<br /><br>apolipoprotein (Apo) A1 and ApoB.<br /><br><br /><br>-HBV virology: hepatitis B surface antigen (HBsAg), HBV core-related antigen<br /><br>(HBcrAg), hepatitis B envelope antigen (HBeAg), HBV DNA (viral load) and HBV<br /><br>pgRNA. </p><br>