Study of ARC-520 in Participants With Hepatitis B Virus e Antigen (HBeAg) Positive Chronic Hepatitis B Virus
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: ARC-520; Placebo; Entecavir; Tenofovir; diphenhydramine
Intervention description: 0.5 or 1.0 mg/day orally; 300 mg/day orally; 50 mg orally as pretreatment antihistamine
Intervention MeSH terms: Diphenhydramine; Promethazine; Tenofovir; Entecavir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Hepatitis B Virus; Chronic Hepatitis B; HBV

Summary:

      Participants with chronic HBV infection will receive multiple doses of ARC-520 in combination
      with entecavir or tenofovir and be evaluated for safety and efficacy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, 18 to 75 years of age

          -  Written informed consent

          -  Body mass index (BMI) between 17.5 and 30.0 kg/m2

          -  No clinically significant abnormalities at screening/pre-dose 12-lead ECG assessment

          -  No abnormal finding of clinical relevance

          -  Diagnosis of HBeAg positive, immune active, chronic HBV infection

          -  > 2 months of continuous treatment with daily oral entecavir or tenofovir

          -  Must use 2 effective methods of contraception (double barrier contraception or
             hormonal contraceptive along with a barrier contraceptive)

        Exclusion Criteria:

          -  Pregnant or lactating

          -  Acute signs of hepatitis/other infection within 4 weeks of screening

          -  Hepatic transaminases (alanine aminotransferase [ALT] or aspartate aminotransferase
             [AST]) > 3 times the upper limits of normal

          -  Liver Elastography (i.e. FibroScan®) score > 9

          -  Antiviral therapy other than entecavir or tenofovir within 3 months of screening

          -  Prior treatment with interferon in the last 3 years

          -  Use of anticoagulants, corticosteroids, immunomodulators, or immunosuppressants within
             6 months of screening

          -  Use within 7 days prior to screening of dietary and/or herbal supplements that can
             interfere with liver metabolism

          -  Use of any drugs known to induce or inhibit hepatic drug metabolism within 30 days of
             study drug administration

          -  Use of prescription medication within 14 days prior to study drug administration

          -  Depot injection/implant of any drug except birth control within 3 months prior to
             study drug administration

          -  Known diagnosis of diabetes mellitus

          -  History of autoimmune disease

          -  Human immunodeficiency virus (HIV) infection

          -  Sero-positive for Hepatitis C Virus (HCV), and/or a history of delta virus hepatitis

          -  Hypertension; blood pressure > 150/100 mmHg

          -  History of cardiac rhythm disturbances

          -  Family history of congenital long QT syndrome, Brugada syndrome or unexplained sudden
             cardiac death

          -  Symptomatic heart failure, unstable angina, myocardial infarction, severe
             cardiovascular disease within 6 months prior to study entry

          -  History of malignancy, except for adequately treated basal cell carcinoma, squamous
             cell skin cancer, superficial bladder tumors, in situ cervical cancer

          -  Major surgery within 3 months of screening

          -  History of alcohol and/or drug abuse < 12 months from screening

          -  Regular use of alcohol within 6 months (ie, more than 14 units of alcohol per week)

          -  Evidence of systemic acute inflammation, sepsis, or hemolysis

          -  Diagnosed with a significant psychiatric disorder

          -  Use of drugs of abuse

          -  History of allergy to bee venom

          -  Positive reaction to the bee venom allergy immunoglobulin E (IgE) test

          -  Use of investigational agents or devices within 30 days

          -  Clinically significant inherited or acquired gastrointestinal pathology, unresolved
             gastrointestinal symptoms, liver or kidney disease

          -  Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction

          -  Clinically significant history or presence of uncontrolled systemic disease

          -  Donated or had a loss of whole blood of 50 milliliters (mL) to 499 mL within 30 days
             or more than 499 mL between 31 and 56 days prior to study treatment

          -  History of fever within 2 weeks of screening

          -  Immunization/planned immunization with live attenuated vaccine except influenza
             vaccine

          -  Presence of any medical or psychiatric condition or social situation that impacts
             compliance or results in additional safety risk

          -  Excessive exercise/physical activity within 7 days of screening/enrolment or during
             study

          -  History of coagulopathy/stroke within past 6 months, and/or concurrent anticoagulant
             medication(s)