A Study of ARC-521 Injection in Normal Adult Volunteers and Patients With Chronic Hepatitis B (CHB)
Condition: Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis
Intervention: ARC-521 Injection; Placebo; antihistamine; acetaminophen; entecavir; tenofovir
Intervention description: 0.9% normal saline; Approximately two hours prior to ARC-521 or placebo administration, 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. Approved antihistamines are: diphenhydramine 50 mg by mouth (PO), chlorpheniramine 8 mg PO, or hydroxyzine 50 mg PO.; Approximately two hours prior to ARC-521 or placebo administration, participants will be pre-treated with acetaminophen (500 - 1000 mg PO, per local strength availability).; Participants take entecavir OR tenofovir daily throughout the study.; Participants take entecavir OR tenofovir daily throughout the study.
Intervention MeSH terms: Acetaminophen; Tenofovir; Entecavir; Histamine Antagonists; Histamine H1 Antagonists
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Normal healthy volunteer (NHV) participants will enroll sequentially into a total of 6
      escalating dose levels (6 subjects per dose level), randomized to receive a single dose of
      ARC-521 Injection or placebo. The maximum study duration for NHVs is approximately 21 weeks.

      Hepatitis B e Antigen (HBeAg)-negative participants with (CHB) will enroll sequentially into
      3 dose levels (8 patients per dose level) to receive multiple doses of open label ARC-521
      Injection. For each CHB participant the maximum study duration is approximately 37 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, 18 to 55 years of age inclusive (NHVs) or 18-65 years of age inclusive
             (CHBs), at the time of informed consent

          -  Able to provide written informed consent prior to the performance of any study
             specific procedures

          -  Body mass index (BMI) between 19.0 and 35.0 kg/m2, inclusive

          -  A 12-lead ECG at Screening and pre-dose assessment that, in the opinion of the
             investigator, has no abnormalities that compromise participant's safety in this study

          -  Must use 2 effective methods of contraception (double barrier contraception or
             hormonal contraceptive along with a barrier contraceptive (both male and female
             partners)

          -  Have suitable venous access for blood sampling

          -  No abnormal finding of clinical relevance at the Screening evaluation (NHVs only)

          -  Have a diagnosis of HbeAg-negative chronic HBV infection (CHB patients only)

          -  Treatment-naive or currently on entecavir/tenofovir for 6 months or longer

        Exclusion Criteria:

          -  Pregnant or lactating

          -  Acute signs of hepatitis/other infection at Screening or at baseline

          -  Use within last 14 days or anticipated requirement for anticoagulants, systemic
             corticosteroids, immunomodulators, or immunosuppressants

          -  Use of prescription medication within 14 days prior to study treatment that in the
             opinion of the PI or the Sponsor would interfere with study conduct.

          -  Known diagnosis of non-alcoholic steatohepatitis [NHVs only] or familial
             hypercholesterolemia

          -  Taking interferon alpha (INFalpha) within 6 months of screening [CHBs only]

          -  History of poorly controlled autoimmune disease or history of autoimmune hepatitis

          -  Human immunodeficiency virus (HIV) infection

          -  Seropositive for HBV (NHVs only) or hepatitis C virus (HCV), and/or history of delta
             virus hepatitis

          -  Hypertension defined as blood pressure > 170/100 mmHg at screening [NHVs only]

          -  A 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 within the last 5 years except for adequately treated basal cell
             carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical
             cancer

          -  History of major surgery within 3 months of Screening

          -  Regular use of alcohol within one month prior to the Screening visit (more than
             fourteen units of alcohol per week)

          -  Evidence of severe systemic acute inflammation, sepsis, or hemolysis [NHVs only]

          -  Use within 3 months of illicit drugs (cocaine, phencyclidine [PCP],
             3,4-methylenedioxymethamphetamine [MDMA], others) or positive test for drugs of abuse
             at screening.

          -  History of allergy to bee venom or history of severe hypersensitivity reaction, such
             as anaphylaxis

          -  Use of an investigational agent or device within 30 days prior to dosing or current
             participation in an investigational study

          -  Clinically significant history of any alcoholic liver disease, cirrhosis, Wilson's
             disease, hemochromatosis, or alpha-1 antitrypsin deficiency, liver or kidney disease

          -  Clinically significant history/presence of poorly controlled or decompensated
             neurological, endocrine, cardiovascular, pulmonary, hematological, immunologic,
             psychiatric, metabolic, or other uncontrolled systemic disease

          -  Blood donation (500 mL) within 7 days prior to study treatment administration [NHVs
             only]

          -  History of fever (>38.0ºC/100.4ºF) within 2 weeks of Screening [NHVs only]

          -  Any concomitant medical or psychiatric condition or social situation that impacts
             compliance or involves additional safety risk

          -  History of coagulopathy (including deep vein thrombosis and pulmonary embolism) or
             stroke within 6 months of baseline, and/or concurrent anticoagulant medication(s)

          -  Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction