<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03272009</url>
  </required_header>
  <id_info>
    <org_study_id>EYP001-103</org_study_id>
    <secondary_id>2017-002211-33</secondary_id>
    <nct_id>NCT03272009</nct_id>
  </id_info>
  <brief_title>Evaluation of the Safety and Pharmacology of EYP001 in HBV Subjects</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled Study to Determine the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the FXR-agonist EYP001a in Chronically HBV Infected Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Enyo Pharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>CPR Pharma Services Pty Ltd, Australia</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Enyo Pharma</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Bile acids regulating farnesoid X receptor (FXR) interact with hepatitis B virus replication.&#xD;
      EYP001a is a selective, synthetic FXR agonist under development for the treatment of&#xD;
      hepatitis B.&#xD;
&#xD;
      This Phase 1b study is designed primarily to determine the safety, tolerability,&#xD;
      pharmacokinetics and pharmacodynamics of EYP001a in chronically HBV infected subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, randomized, double-blind, placebo-controlled two-part trial.&#xD;
&#xD;
      In Part A, EYP001a will be administered as 29 days monotherapy. Three dose-levels and 2&#xD;
      dosing regimens of EYP001a will be explored against placebo. The design also includes an&#xD;
      open-label standard of care Entecavir monotherapy arm (comparator). Subjects will be randomly&#xD;
      assigned to one of the 6 treatment arms:&#xD;
&#xD;
        -  Treatment A: oral EYP001a&#xD;
&#xD;
        -  Treatment B: oral EYP001a&#xD;
&#xD;
        -  Treatment C: oral EYP001a&#xD;
&#xD;
        -  Treatment D: oral EYP001a&#xD;
&#xD;
        -  Treatment E: oral placebo&#xD;
&#xD;
        -  Treatment F: oral Entecavir&#xD;
&#xD;
      In Part B, EYP001a or placebo will be administered as 29 days combination therapy with the&#xD;
      standard of care Peg-IFNα2a. Subjects will be randomly assigned to one of the 3 treatment&#xD;
      arms:&#xD;
&#xD;
        -  Treatment G: oral EYP001a plus open label Peg-INFα2a administered as subcutaneous&#xD;
           injection&#xD;
&#xD;
        -  Treatment H: oral EYP001a plus open label Peg-INFα2a administered as subcutaneous&#xD;
           injection&#xD;
&#xD;
        -  Treatment I: oral placebo plus open label Peg-INFα2a administered as subcutaneous&#xD;
           injection&#xD;
&#xD;
      Subjects enrolled in Part A are eligible for participation in Part B.&#xD;
&#xD;
      Participation will include a 40 day screening period, a 29 day treatment period and a 6 day&#xD;
      follow-up evaluation period. For subjects who participate in both Parts A and B, a 14 washout&#xD;
      period between Parts A and B will be included.&#xD;
&#xD;
      The safety and tolerability of EYP001a will be assessed by evaluating physical examinations,&#xD;
      vital signs, ECGs, clinical laboratory parameters, and adverse events.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 21, 2017</start_date>
  <completion_date type="Actual">July 30, 2018</completion_date>
  <primary_completion_date type="Actual">July 30, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Type and frequencies of adverse events</measure>
    <time_frame>Day 1 through Day 35</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma concentration (Cmax) of EYP001</measure>
    <time_frame>Day 1 through Day 35</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach maximum concentration (Tmax) after EYP001 administration</measure>
    <time_frame>Day 1 through Day 35</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve from time 0 to last measurable concentration (AUC0-6h) of EYP001</measure>
    <time_frame>Day 1 through Day 35</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bile acid precursor C4 (7αhydroxy-4-cholesten-3-one)</measure>
    <time_frame>Day 1 through Day 35</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fibroblast growth factor 19 (FGF19)</measure>
    <time_frame>Day 1 through Day 35</time_frame>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Actual">73</enrollment>
  <condition>Hepatitis B, Chronic</condition>
  <arm_group>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral EYP001a</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral EYP001a</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral EYP001a</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral EYP001a</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment E</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>oral placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment F</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>oral Entecavir</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment G</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral EYP001a plus subcutaneous injection of Peg-INFα2a</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment H</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral EYP001a plus subcutaneous injection of Peg-INFα2a</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment I</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>oral placebo plus subcutaneous injection of Peg-INFα2a</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EYP001a</intervention_name>
    <description>Capsules administered orally. Number of morning and evening capsules depending on treatment arm</description>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_label>Treatment D</arm_group_label>
    <arm_group_label>Treatment G</arm_group_label>
    <arm_group_label>Treatment H</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo capsules for oral administration, identical in appearance to the EYP001a capsules</description>
    <arm_group_label>Treatment E</arm_group_label>
    <arm_group_label>Treatment I</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Entecavir</intervention_name>
    <description>Tablets administered orally</description>
    <arm_group_label>Treatment F</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>peg-interferon alfa-2a</intervention_name>
    <description>Ready-to-Use pre-filled syringes for subcutaneous injection</description>
    <arm_group_label>Treatment G</arm_group_label>
    <arm_group_label>Treatment H</arm_group_label>
    <arm_group_label>Treatment I</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Have given voluntary written informed consent;&#xD;
&#xD;
          2. Have a documented medical history of chronic HBV infection (within 12 months of&#xD;
             screening visit), both results:&#xD;
&#xD;
               -  Documented positive hepatitis B surface antigen (HBsAg) and&#xD;
&#xD;
               -  Documented HBV DNA &gt; 1000 IU/mL&#xD;
&#xD;
          3. Is anti-HBV treatment naive or treatment experienced (see also exclusion criterion&#xD;
             #3).&#xD;
&#xD;
          4. Gender: male or female.&#xD;
&#xD;
          5. Age: 18 to 65 years inclusive.&#xD;
&#xD;
          6. Body mass index (BMI): 17.0-35.0 kg/m2 inclusive.&#xD;
&#xD;
          7. Has clinical chemistry, hematology, coagulation and urinalysis tests within normal,&#xD;
             allowable limits (with the exception of alanine aminotransferase [ALT]); see inclusion&#xD;
             criterion #10); if there is an out of range value, the result must be considered&#xD;
             clinically non-significant by the investigator in order to be eligible.&#xD;
&#xD;
          8. Vital signs after at least 5 minutes resting in supine position at screening within&#xD;
             the following ranges:&#xD;
&#xD;
               -  systolic blood pressure: between 90 mm Hg and 145 mm Hg&#xD;
&#xD;
               -  diastolic blood pressure: between 45 mm Hg and 90 mm Hg&#xD;
&#xD;
               -  heart rate: between 40 bpm and 100 bpm&#xD;
&#xD;
          9. Have no clinically significant abnormal 12-lead automatic electrocardiogram (ECG)&#xD;
             (incomplete right bundle branch block can be accepted) at screening: PR interval&#xD;
             between 120 ms -and 210 ms, QRS-duration &lt; 120 ms, QTc-interval (Fridericia's) ≤ 450&#xD;
             msec.&#xD;
&#xD;
         10. ALT at screening ≤ 5 x upper limit of normal (ULN).&#xD;
&#xD;
         11. Agrees to abstain from all medication, including non-prescription and prescription&#xD;
             medication for 28 days prior to the Day 1 study visit, except for authorized&#xD;
             medications (such as hormonal contraceptives for females, vitamins prescribed per&#xD;
             label dosages and paracetamol). On a case-by-case basis, regular co-medication either&#xD;
             as defined on the medication exception list or as documented by written approval from&#xD;
             the sponsor as acceptable prior to randomization, will not be considered as a&#xD;
             deviation from this criterion.&#xD;
&#xD;
         12. At screening, females must be non-pregnant and non-lactating, or of non-childbearing&#xD;
             potential (either surgically sterilized or physiologically incapable of becoming&#xD;
             pregnant, or at least 1 year post-menopausal [amenorrhea duration of 12 consecutive&#xD;
             months); non-pregnancy will be confirmed for all females by a pregnancy test conducted&#xD;
             at screening and at follow-up visit.&#xD;
&#xD;
         13. Female subjects of child-bearing potential, with a fertile male sexual partner, should&#xD;
             be willing to use adequate contraception from screening until 90 days after the&#xD;
             follow-up visit. Adequate contraception is defined as using hormonal contraceptives or&#xD;
             an intrauterine device combined with at least 1 of the following forms of&#xD;
             contraception: a diaphragm or cervical cap, or a condom. Also, total abstinence, in&#xD;
             accordance with the lifestyle of the subject, is acceptable.&#xD;
&#xD;
         14. Male subjects, if not surgically sterilized, should be willing to use adequate&#xD;
             contraception and not donate sperm from the Day 1 visit to the clinical research&#xD;
             centre until 90 days after the follow-up visit. Adequate contraception for the male&#xD;
             subject (and his female partner) is defined as using hormonal contraceptives or an&#xD;
             intrauterine device combined with at least 1 of the following forms of contraception:&#xD;
             a diaphragm or cervical cap, or a condom. Also, total abstinence, in accordance with&#xD;
             the lifestyle of the subject is acceptable.&#xD;
&#xD;
         15. At screening, has no recent (&lt;3 months) history of any clinically significant&#xD;
             conditions, which, in the opinion of the investigator, would jeopardize the safety of&#xD;
             the subject or impact the validity of the study results.&#xD;
&#xD;
         16. Willingness to abstain from alcohol from 48 hours prior to each study visit to the&#xD;
             clinical research centre.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Employee of a CRO participating in this study or the Sponsor.&#xD;
&#xD;
          2. Has certain or probable compensated liver cirrhosis documented by at least 2 of the&#xD;
             following:&#xD;
&#xD;
               1. Optional assessment: has documented liver histology Metavir score (F4), Ishak &gt;5&#xD;
                  or Scheuer (F4)&#xD;
&#xD;
               2. Mandatory assessment: has presence or history of ascites, spontaneous bacterial&#xD;
                  peritonitis, esophageal varices, hepatic encephalopathy&#xD;
&#xD;
               3. Mandatory assessment: platelet count below 90,000/uL within 12 months of&#xD;
                  screening visit&#xD;
&#xD;
               4. Optional assessment: positive indirect blood test of APRI or FIB4 or positive&#xD;
                  direct blood test Fibrosure, Fibrotest, or FibroSpect within 12 months of&#xD;
                  screening visit&#xD;
&#xD;
               5. Optional assessment: has positive elastography within 6 months of screening visit&#xD;
                  (Fibroscan or Shearwave Aixplorer)&#xD;
&#xD;
               6. Optional assessment: has abnormal liver imaging (CT/US/MRI) consistent with a&#xD;
                  lobular/nodular liver and cirrhosis or indirect signs of portal hypertension.&#xD;
&#xD;
          3. Subject is HBV treatment experienced AND currently on anti-HBV treatment during the 30&#xD;
             days (or 5 half-lives of the considered anti-HBV drug, whichever is longer) before the&#xD;
             first investigational product administration and until the last study visit.&#xD;
&#xD;
          4. Co-infection with active hepatitis C virus (HCV, except for patients with sustained&#xD;
             viral response SVR, who can be included).&#xD;
&#xD;
          5. Co-infection with human immunodeficiency virus (HIV) Note: hepatitis D virus (HDV)&#xD;
             status is not required for randomization and if not available can be established&#xD;
             during the Day 1 visit with baseline PD virology assessments.&#xD;
&#xD;
          6. Receives or plans to receive systemic immunosuppressive or immunomodulating&#xD;
             medications (e.g. IFN) during the study or ≤ 4 months prior to the first&#xD;
             investigational product administration.&#xD;
&#xD;
          7. Has clinically relevant immunosuppression from, but not limited to immunodeficiency&#xD;
             conditions such as common variable hypogammaglobulinemia.&#xD;
&#xD;
          8. Clinical diagnosis of substance abuse during ≤ 12 months prior to screening with&#xD;
             narcotics or cocaine or with alcohol (regular consumption &gt; 21 units/week [men] and &gt;&#xD;
             14 units/week [women]; 1 unit = 1⁄2 pint of beer, 25 mL shot of 40% spirit or a 125 mL&#xD;
             glass of wine. Expressed in g/day: &gt; 30 g/day [men] and &gt; 20 g/day [women]).&#xD;
&#xD;
          9. Has a positive drug urine screen (cocaine, phencyclidine, amphetamines (incl.&#xD;
             methamphetamines), opiates (incl. heroin, codeine and morphine), benzodiazepines,&#xD;
             barbiturates, methadone or alcohol screen. Subjects who admit the occasional use of&#xD;
             cannabis will not be excluded as long as they are able to abstain from cannabis when&#xD;
             they are assessed at study visits.&#xD;
&#xD;
         10. Has any known pre-existing medical or psychiatric condition that could interfere with&#xD;
             the subject's ability to provide informed consent or participate in study conduct, or&#xD;
             that may confound study findings.&#xD;
&#xD;
         11. Has a history of long QT syndrome.&#xD;
&#xD;
         12. Has a history of clinically significant gastrointestinal disease, especially peptic&#xD;
             ulcerations, gastrointestinal bleeding, ulcerative colitis, Crohn's disease or&#xD;
             Inflammatory Bowel Syndrome, renal, hepatic, neurologic, hematologic, endocrine,&#xD;
             oncologic, pulmonary, immunologic, or cardiovascular disease or any other condition&#xD;
             which, in the opinion of the investigator, would jeopardize the safety of the subject&#xD;
             or impact the validity of the study results.&#xD;
&#xD;
         13. Has participated in any drug study within 40 days prior to the first drug&#xD;
             administration in the current study. Note: Part A participation to this study is&#xD;
             acceptable and not an exclusion criteria when considering eligibility for Part B,&#xD;
             under the condition that follow-up visit of Part A has been completed and no&#xD;
             investigational product related SAEs have occurred during Part A.&#xD;
&#xD;
         14. Has an uncontrolled ongoing illness at screening (e.g., active viral infection).&#xD;
&#xD;
         15. Has had major surgery within 30 days prior to the first drug administration, or within&#xD;
             6 months for gastrointestinal surgery prior to the first drug administration.&#xD;
&#xD;
         16. Has a history of relevant drug and/or food allergies.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Henk W Reesink, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Academic Medical Centre AMC Amsterdam</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stephan Riordan</last_name>
    <role>Principal Investigator</role>
    <affiliation>Scientia Clinical Research Limited Sydney</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Scientia Clinical Research Limited</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linear Clinical Research Limited</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Academic Medical Centre (AMC)</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus MC</name>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinika Chorób Zakaźnych I Hepatologii UMB</name>
      <address>
        <city>Białystok</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinika Chorób Zakaźnych</name>
      <address>
        <city>Kielce</city>
        <zip>25-317</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HepID</name>
      <address>
        <city>Lublin</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King Chulalongkorn Memorial Hospital</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital for Tropical Diseases</name>
      <address>
        <city>Bangkok</city>
        <zip>10400</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Thailand</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>August 20, 2018</last_update_submitted>
  <last_update_submitted_qc>August 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis B, Chronic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interferons</mesh_term>
    <mesh_term>Interferon-alpha</mesh_term>
    <mesh_term>Interferon alpha-2</mesh_term>
    <mesh_term>Entecavir</mesh_term>
    <mesh_term>Peginterferon alfa-2a</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03272009
org study id: EYP001-103
secondary id: 2017-002211-33
nct id: NCT03272009
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Bile acids regulating farnesoid X receptor (FXR) interact with hepatitis B virus replication.
      EYP001a is a selective, synthetic FXR agonist under development for the treatment of
      hepatitis B.

      This Phase 1b study is designed primarily to determine the safety, tolerability,
      pharmacokinetics and pharmacodynamics of EYP001a in chronically HBV infected subjects.
This is a multicenter, randomized, double-blind, placebo-controlled two-part trial.

      In Part A, EYP001a will be administered as 29 days monotherapy. Three dose-levels and 2
      dosing regimens of EYP001a will be explored against placebo. The design also includes an
      open-label standard of care Entecavir monotherapy arm (comparator). Subjects will be randomly
      assigned to one of the 6 treatment arms:

        -  Treatment A: oral EYP001a

        -  Treatment B: oral EYP001a

        -  Treatment C: oral EYP001a

        -  Treatment D: oral EYP001a

        -  Treatment E: oral placebo

        -  Treatment F: oral Entecavir

      In Part B, EYP001a or placebo will be administered as 29 days combination therapy with the
      standard of care Peg-IFNα2a. Subjects will be randomly assigned to one of the 3 treatment
      arms:

        -  Treatment G: oral EYP001a plus open label Peg-INFα2a administered as subcutaneous
           injection

        -  Treatment H: oral EYP001a plus open label Peg-INFα2a administered as subcutaneous
           injection

        -  Treatment I: oral placebo plus open label Peg-INFα2a administered as subcutaneous
           injection

      Subjects enrolled in Part A are eligible for participation in Part B.

      Participation will include a 40 day screening period, a 29 day treatment period and a 6 day
      follow-up evaluation period. For subjects who participate in both Parts A and B, a 14 washout
      period between Parts A and B will be included.

      The safety and tolerability of EYP001a will be assessed by evaluating physical examinations,
      vital signs, ECGs, clinical laboratory parameters, and adverse events.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Type and frequencies of adverse events
time frame: Day 1 through Day 35
measure: Maximum plasma concentration (Cmax) of EYP001
time frame: Day 1 through Day 35
measure: Time to reach maximum concentration (Tmax) after EYP001 administration
time frame: Day 1 through Day 35
measure: Area under the concentration-time curve from time 0 to last measurable concentration (AUC0-6h) of EYP001
time frame: Day 1 through Day 35
measure: Bile acid precursor C4 (7αhydroxy-4-cholesten-3-one)
time frame: Day 1 through Day 35
measure: Fibroblast growth factor 19 (FGF19)
time frame: Day 1 through Day 35
arm group label: Treatment A
arm group type: Experimental
description: oral EYP001a
arm group label: Treatment B
arm group type: Experimental
description: oral EYP001a
arm group label: Treatment C
arm group type: Experimental
description: oral EYP001a
arm group label: Treatment D
arm group type: Experimental
description: oral EYP001a
arm group label: Treatment E
arm group type: Placebo Comparator
description: oral placebo
arm group label: Treatment F
arm group type: Active Comparator
description: oral Entecavir
arm group label: Treatment G
arm group type: Experimental
description: oral EYP001a plus subcutaneous injection of Peg-INFα2a
arm group label: Treatment H
arm group type: Experimental
description: oral EYP001a plus subcutaneous injection of Peg-INFα2a
arm group label: Treatment I
arm group type: Placebo Comparator
description: oral placebo plus subcutaneous injection of Peg-INFα2a
intervention type: Drug
intervention name: EYP001a
description: Capsules administered orally. Number of morning and evening capsules depending on treatment arm
arm group label: Treatment A
arm group label: Treatment B
arm group label: Treatment C
arm group label: Treatment D
arm group label: Treatment G
arm group label: Treatment H
intervention type: Drug
intervention name: Placebo
description: Placebo capsules for oral administration, identical in appearance to the EYP001a capsules
arm group label: Treatment E
arm group label: Treatment I
intervention type: Drug
intervention name: Entecavir
description: Tablets administered orally
arm group label: Treatment F
intervention type: Drug
intervention name: peg-interferon alfa-2a
description: Ready-to-Use pre-filled syringes for subcutaneous injection
arm group label: Treatment G
arm group label: Treatment H
arm group label: Treatment I
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Henk W Reesink, MD
role: Principal Investigator
affiliation: Academic Medical Centre AMC Amsterdam
last name: Stephan Riordan
role: Principal Investigator
affiliation: Scientia Clinical Research Limited Sydney
facility: 
facility: 
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facility: 
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country: Australia
country: Netherlands
country: Poland
country: Thailand
responsible party type: Sponsor
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Interferons
mesh term: Interferon-alpha
mesh term: Interferon alpha-2
mesh term: Entecavir
mesh term: Peginterferon alfa-2a