Study of ARC-520 in Patient With Chronic Hepatitis B Virus

Study Overview
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Brief Summary
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Patients with chronic HBV infection will receive ARC-520 in combination with entecavir or tenofovir and be evaluated for safety and efficacy.

Detailed Description
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This is a single-center, open-label study of ARC-520 in combination with entecavir or tenofovir administered to patients with immune active chronic HBV infection. An iterative trial design is anticipated with potential inclusion of additional cohorts with anticipated enrollment of up to 60 patients. Patients who have signed a Human Research Ethics Committee approved informed consent, and have met all of the protocol eligibility criteria will continue receiving daily oral entecavir (0.5-1.0 mg/day) or daily oral tenofovir (300 mg/day) and a single IV injection of ARC-520. If a serious adverse event (SAE) deemed possibly or probably related to study drug should occur at any point during the study, any further dosing will be put on hold pending a complete review of safety data by the sponsor and the Principal Investigator. Patients will undergo the following evaluations at regular intervals during the study: medical history, physical examinations, vital sign measurements (blood pressure, heart rate, respiratory rate, and temperature), weight, AEs, 12-lead ECGs, concomitant medication, blood sample collection for hematology, coagulation, chemistry, PK and exploratory PD measures, HBV virology. Patients will be monitored for a total of 12 weeks. Clinically significant changes including AEs will be followed until resolution, until the condition stabilizes, until the event is otherwise explained, or until the patient is lost to follow-up.

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: ARC-520 Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 to 65 years of age Written informed consent No clinically significant abnormalities at screening/pre-dose 12-lead ECG assessment No abnormal finding of clinical relevance Diagnosis of immune active chronic HBV infection > 6 months of continuous treatment with daily, oral entecavir or tenofovir 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 or a toll receptor agonist in last 12 months Use of anticoagulants, corticosteroids, immunomodulators, or immunosuppressants Use of dietary and/or herbal supplements that can interfere with liver metabolism Use of any drugs known to induce or inhibit hepatic drug metabolism Use of prescription medication or over-the-counter products Depot injection/implant of any drug except birth control. Known diagnosis of diabetes mellitus. History of autoimmune disease Human immunodeficiency virus (HIV) infection Sero-positive for HCV, and/or history of delta virus hepatitis Hypertension: blood pressure > 150/100 mmHg History of cardiac rhythm disturbances Family history of congenital long QT syndrome/unexplained sudden cardiac death Symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease History of malignancy, except 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 Regularly uses alcohol within past 6 months (ie, more than 14 units of alcohol per week) Evidence of acute inflammation, sepsis, or hemolysis Diagnosed with a significant psychiatric disorder Use of drugs of abuse History of allergy to bee venom Use of investigational agents/devices within 30 days Current participation in an investigational study Clinically significant gastrointestinal pathology, unresolved gastrointestinal symptoms, liver or kidney disease History/presence of Gilbert's syndrome, conditions that interfere with absorption, distribution, metabolism, excretion of drugs Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction Clinically significant history/presence of uncontrolled systemic disease Donated blood (500 mL) within 7 days prior to study treatment administration History of fever within 2 weeks of screening Immunization/planned immunization with live attenuated vaccine except influenza vaccine Excessive exercise/physical activity within 7 days of screening/enrolment or during study History of coagulopathy or stroke within past 6 months, and/or concurrent anticoagulants

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>ARC-520 Injection | Drug: ARC-520 Injection<br>* ARC-520 Injection is a liver-targeted antiviral therapeutic designed to treat chronic hepatitis B virus (HBV) infection via an RNA interference (RNAi) mechanism.<br>* Other names: ARC-520;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: To evaluate the depth and duration of HBsAg decline in response to a single dose of ARC 520 in combination with entecavir or tenofovir in patients with chronic HBV infection |  | Through Day 85 post-dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety:To determine the safety and tolerability of ARC 520 through monitoring of adverse events, vital signs, physical exam changes, blood sampling for hematology, coagulation and chemistry and 12-lead ECGs |  | Through Day 85 post-dosing | 
| Pharmacokinetic parameters: Cmax, AUC0-24, AUClast, AUCinf, CL, V=CL/kel, kel, t1/2 | Blood samples collected immediately prior to infusion and immediately prior to end of infusion, and 0.5,1,3,6,24,48 hrs post-infusion. | Post dosing on Days 1,2 & 3 | 
| Allergenicity:Evaluate Allergenicity of ARC-520 through Bee Venom Allergy Test (IgE) |  | Within 30 days prior to first dose and at Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B, HBV infection, Hepatitis B Surface Antigen