Study of ARC-520 With or Without Other Drugs Used in the Treatment of Chronic Chronic Hepatitis B Virus (HBV)
Condition: Hepatitis B; Hepatitis D
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis D; Hepatitis
Intervention: ARC-520; entecavir; pegylated interferon alpha 2a; tenofovir disoproxil; antihistamine
Intervention description: ARC-520 will be administered intravenously concomitantly with 0.9% normal saline using an infusion rate of 0.4 mL/min (24 mL/hour) for study treatment and 200 mL/hr for saline.; 0.5 mg once daily; oral; 180 mcg; subcutaneous injection once weekly; 300 mg once daily; oral; All participants will be pre-treated with an oral antihistamine selected by the investigator from the list of approved antihistamines that is available in that country. Acceptable antihistamines are: diphenhydramine 50 mg p.o., chlorpheniramine 8 mg p.o., hydroxyzine 50 mg p.o., or cetirizine 10 mg p.o.
Intervention MeSH terms: Interferons; Tenofovir; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a; Entecavir; Histamine Antagonists; Histamine H1 Antagonists
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 79.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      Patients with chronic HBV infection will receive either ARC-520 alone or ARC-520 in
      combination with other treatments such as entecavir (ENT) or tenofovir (TDF) and/or pegylated
      interferon (PEG IFN) alpha 2a therapy, 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

          -  Diagnosis of HBeAg negative or positive chronic HBV infection.

          -  Must be HBsAg (+) during screening.

          -  Must be treatment naïve: never on PEG IFN alpha 2a and/or ETV or TDF; and

          -  Have not used nucleoside/nucleotide analogs (NUCs) within the last 2 years prior to
             dosing on Day 1

          -  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 severe infections within 4 weeks of screening

          -  Use within the last 14 days or anticipated requirement for anticoagulants, systemic
             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, over-the-counter (OTC) and prescription pain medication or
             hormonal contraceptives

          -  History of poorly controlled autoimmune disease or any history of autoimmune hepatitis

          -  History of heterozygous or homozygous familial hypercholesterolemia.

          -  Human immunodeficiency virus (HIV) infection

          -  Is sero-positive for Hepatitis C Virus (HCV), or has a history of delta virus
             hepatitis (except for cohort in which delta virus infection is acceptable)

          -  Has hypertension: blood pressure > 170/100 mmHg; well-controlled blood pressure on
             hypertensive medication allowed

          -  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, or in situ cervical cancer

          -  Has had major surgery within 1 month of screening

          -  Regular use of alcohol within 6 months prior to screening (ie, more than 14 units of
             alcohol per week)

          -  Use of recreational drugs such as cocaine, phencyclidine (PCP), and methamphetamines,
             within 1 year prior to the screening

          -  History of allergy to bee sting

          -  Clinically significant history of any alcoholic liver disease, cirrhosis, Wilson's
             disease, hemochromatosis, or alpha-1 antitrypsin deficiency

          -  Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction

          -  Clinically significant history or presence of poorly controlled/uncontrolled systemic
             disease

          -  Presence of any medical or psychiatric condition or social situation that impacts
             compliance or results in additional safety risk

          -  History of coagulopathy/stroke within past 6 months, and/or concurrent anticoagulant
             medication(s)