A Multi-dose Study of ARC-520 in Patients With Hepatitis B 'e' Antigen (HBeAg) Negative, Chronic Hepatitis B Virus (HBV) Infection
Condition: Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis
Intervention: ARC-520 Injection; placebo; entecavir; tenofovir; antihistamine
Intervention description: ARC-520 Injection was administered concomitantly, IV with 0.9% normal saline using an infusion rate of 0.4 mL/min for study treatment and 3.6 mL/min for saline.; Placebo was administered concomitantly, IV with 0.9% normal saline using an infusion rate of 0.4 mL/min for study treatment and 3.6 mL/min for saline.; All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.; All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.; All participants will be pretreated with an oral antihistamine, administered 2 hours (±30 minutes) pre-dose. The antihistamine used should in general be an H1>H2 receptor blocker and would include diphenhydramine 50 mg, cetirizine 10 mg, chlorpheniramine 8 mg or hydroxyzine 50 mg. The Investigator is free to choose any of these antihistamines available locally and consistent with their country's Marketing Authorisation.
Intervention MeSH terms: Tenofovir; Entecavir; Histamine Antagonists; Histamine H1 Antagonists
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 58.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      Patients with chronic HBV infection will receive either ARC-520 or placebo 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

          -  No clinically significant abnormalities at screening/pre-dose 12-lead ECG assessment

          -  No new abnormal finding of clinical relevance at the screening evaluation.

          -  Diagnosis of HBeAg negative, immune active, chronic HBV infection

          -  > 2 months of continuous treatment with daily, oral entecavir or tenofovir

          -  Willingness to continue taking entecavir or tenofovir throughout the study.

          -  Must use 2 effective methods of contraception (double barrier contraception or
             hormonal contraceptive along with a barrier contraceptive) (both male and female
             partners)

        Exclusion Criteria:

          -  Pregnant or lactating

          -  Acute signs of hepatitis/other infection within 4 weeks of screening

          -  Antiviral therapy other than entecavir or tenofovir within 3 months of screening

          -  Prior treatment with interferon in the last 3 years.

          -  Use within the last 6 months or anticipated requirement for anticoagulants,
             corticosteroids, immunomodulators, or immunosuppressants.

          -  Use of prescription medication within 14 days prior to treatment administration
             except: topical products without systemic absorption, statins (except rosuvastatin),
             hypertension medications, or hormonal contraceptives.

          -  Depot injection or implant of any drug within 3 months prior to treatment
             administration, except injectable/implantable birth control.

          -  Diagnosis of diabetes mellitus.

          -  History of autoimmune disease especially autoimmune hepatitis.

          -  Human immunodeficiency virus (HIV) infection.

          -  Sero-positive for Hepatitis C Virus (HCV), and/or a history of delta virus hepatitis.

          -  Hypertension defined as blood pressure > 150/100 mmHg

          -  History of cardiac rhythm disturbances

          -  Family history or 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, or in situ cervical cancer.

          -  Has had a major surgery within 3 months of screening.

          -  History of alcohol and/or drug abuse < 12 months from screening.

          -  Regular uses of alcohol within 6 months prior to screening (ie, more than 14 units of
             alcohol per week).

          -  Evidence of severe systemic acute inflammation, sepsis, or hemolysis.

          -  Diagnosed with a significant psychiatric disorder.

          -  Use of recreational drugs, such as marijuana, within 3 months prior to screening

          -  Use of drugs such as cocaine, phencyclidine (PCP), and methamphetamines, within 1 year
             prior to screening.

          -  History of allergy to bee sting.

          -  Use of investigational agents or devices within 30 days prior to planned study dosing
             or current participation in an investigational study.

          -  Clinically significant history or presence of any gastrointestinal pathology,
             unresolved gastrointestinal symptoms, liver or kidney disease.

          -  Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction.

          -  Clinically significant history or presence of poorly controlled/uncontrolled systemic
             disease.

          -  History of fever within 2 weeks of screening.

          -  Immunized with a live attenuated vaccine within 7 days prior to dosing or planned
             vaccination (excluding flu vaccine by injection).

          -  Presence of any medical or psychiatric condition or social situation that impacts
             compliance or results in additional safety risk.

          -  Participated in excessive exercise/physical activity within 7 days of screening or
             planned during the trial.

          -  History of coagulopathy/stroke within past 6 months, and/or concurrent anticoagulant
             medication(s).