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.
This is a multicenter, randomized, double-blind, placebo-controlled, multi-dose study of ARC-520 in combination with entecavir or tenofovir administered to patients with Hepatitis B 'e' Antigen (HBeAg) negative and immune active chronic HBV infection. Eligible patients who have signed an Ethics Committee - approved informed consent, will be enrolled and will receive ARC-520 or placebo in combination with entecavir or tenofovir. The study will enroll up to a total of 60 eligible chronic HBV infected patients. 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, adverse events assessment (AEs), 12-lead electrocardiograms (ECGs), liver fibrosis testing, concomitant medication assessment, blood sample collection for hematology, coagulation,chemistry, lactate, Pharmacokinetic (PK) measures (in a subset of patients), exploratory Pharmacodynamic (PD) measures, urinalysis, HBV serology, Follicle Stimulating Hormone (FSH) testing (post-menopausal females) and pregnancy testing for females of childbearing potential. 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. For each patient, the duration of the study is approximately 33 weeks from screening to the Day 169 follow-up visit. For patients enrolling into a planned extension study, the total duration of this study is approximately 25 weeks from screening to Day 113 end of study visit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
58
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.
Research Site 1
Hong Kong, China
Research Site 2
Hong Kong, China
Research Site 11
Frankfurt, Germany
Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 113
Change From Baseline in log qHBsAg at Day 113 in response to multiple doses of ARC-520 versus placebo, using a a mixed effect model for repeated measures (MMRM). Includes parameter baseline as a continuous covariate, and treatment and visit as fixed factors, interaction of treatment and visit, and interaction of parameter baseline and visit.
Time frame: Baseline, Day 113
Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time
Change From Baseline in log qHBsAg at Day 113 in response to multiple doses of ARC-520 versus placebo, using a a mixed effect model for repeated measures (MMRM). Includes parameter baseline as a continuous covariate, and treatment and visit as fixed factors, interaction of treatment and visit, and interaction of parameter baseline and visit.
Time frame: Baseline, Day 15, 29, 43, 57, 71, 85, 99
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs
An AE is any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. An SAE is any AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is a medically important event or reaction. A treatment emergent AE (TEAE) was defined as an AE that was not present prior to the first study medication administration and started at/after the time of initiation of administration of study medication, or an AE which was present prior to initiation of study medication administration, which increased in severity after study medication administration.
Time frame: Through Day 169
Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
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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.
Research Site 9
Hamburg, Germany
Research Site 8
Hanover, Germany
Research Site 10
Leipzig, Germany
Research Site 4
Leipzig, Germany
Research Site 5
München, Germany
Research Site 3
Tübingen, Germany
Research Site 6
Ulm, Germany
...and 6 more locations
Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
Pharmacokinetics of ARC-520: Maximum Observed Plasma Concentration (Cmax)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
Pharmacokinetics of ARC-520: Clearance (CL)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
Pharmacokinetics of ARC-520: Apparent Volume of Distribution (V)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
Pharmacokinetics of ARC-520: Terminal Elimination Rate Constant (Kel)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
Pharmacokinetics of ARC-520: Terminal Elimination Half-Life (t1/2)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85