Clinical trial NCT03272009 (phase 1, status: completed)
Conditions: hepatitis b, chronic
ICD codes: B18.0, B18.1, B18.2, B18.8, B18.9
Drugs: eyp001a, placebo, entecavir, peg-interferon alfa-2a
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CCOC(=O)C1=CC=C(N)C=C1
Eligibility criteria:

        Inclusion Criteria:

          1. Have given voluntary written informed consent;

          2. Have a documented medical history of chronic HBV infection (within 12 months of
             screening visit), both results:

               -  Documented positive hepatitis B surface antigen (HBsAg) and

               -  Documented HBV DNA > 1000 IU/mL

          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
             between 120 ms -and 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 (either surgically sterilized 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 by a pregnancy test conducted
             at screening and at follow-up 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
             follow-up 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. Also, total abstinence, in
             accordance with the lifestyle of the subject, is acceptable.

         14. Male subjects, if not surgically sterilized, should be willing to use adequate
             contraception and not donate sperm from the Day 1 visit to the clinical research
             centre until 90 days after the follow-up visit. Adequate contraception for the male
             subject (and his female partner) 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. Also, total abstinence, in accordance with
             the lifestyle of the subject is acceptable.

         15. At screening, has no recent (<3 months) history of any clinically significant
             conditions, which, in the opinion of the investigator, would jeopardize the safety of
             the subject or impact the validity of the study results.

         16. Willingness to abstain from alcohol from 48 hours prior to each study visit to the
             clinical research centre.

        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:

               1. Optional assessment: has documented liver histology Metavir score (F4), Ishak >5
                  or Scheuer (F4)

               2. Mandatory assessment: has presence or history of ascites, spontaneous bacterial
                  peritonitis, esophageal varices, hepatic encephalopathy

               3. Mandatory assessment: platelet count below 90,000/uL within 12 months of
                  screening visit

               4. 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

               5. Optional assessment: has positive elastography within 6 months of screening visit
                  (Fibroscan or Shearwave Aixplorer)

               6. 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 a history of long QT syndrome.

         12. 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 impact the validity of the study results.

         13. Has participated in any drug study within 40 days prior to the first drug
             administration in the current study. Note: Part A participation to this study is
             acceptable and not an exclusion criteria when considering eligibility for Part B,
             under the condition that follow-up visit of Part A has been completed and no
             investigational product related SAEs have occurred during Part A.

         14. Has an uncontrolled ongoing illness at screening (e.g., active viral infection).

         15. Has had major surgery within 30 days prior to the first drug administration, or within
             6 months for gastrointestinal surgery prior to the first drug administration.

         16. Has a history of relevant drug and/or food allergies.