A study to determine the safety and anti-viral activity of ARB-1740 in patients with chronic hepatitis B virus (HBV) infection.

INTERVENTION: Intervention name: ARB‐1740 for the treatment of chronic hepatitis B virus infection. Intervention description: Approximately 30 HBeAg‐negative, non–cirrhotic subjects will be enrolled in three sequential cohorts; each cohort will include approximately 10 subjects, randomized 4:1 to treatment with ARB‐1740 or placebo. Cohort 1 (0.05 mg/kg): All subjects will be HBV‐DNA Positive and either treatment experienced or treatment naive. Cohort 2 (0.1 mg/kg) and Cohort 3 (0.2 mg/kg): All subjects will be virally suppressed (HBV‐DNA Negative), and receiving nucleos(t)ide analogue (NA) therapy for at least 12 months. A premedication regimen will be used prior to each dose of ARB‐1740. Briefly: anti‐inflammatory medication will be administered 8‐12 hours prior to study treatment infusion; anti‐inflammatory and antihistamine medication will be administered 30 minutes prior to study treatment infusion. For each cohort, ARB‐1740 or placebo will be administered as a 2‐hour intravenous infusion. Subjects will receive ARB‐1740 or placebo on Days 1, 29 and 57 (End of Treatment [EOT] Visit). All subjects will be followed for at least 24 weeks after the EOT Visit. At each visit, subjects will be asked by the site personnel about their state of health and use of any concomitant medication since Screening or since the previous study visit. They will also be questioned about their adherence with study restrictions. CONDITION: Chronic hepatitis B virus infection PRIMARY OUTCOME: Composite Primary Outcome: The frequency and severity of treatment‐emergent adverse events (AEs), discontinuations due to AEs, and laboratory abnormalities, by cohort, in HBV‐DNA Negative (‐) subjects, assessed through continuous monitoring by the Investigator. ; ; Possible AEs may include infusion related reactions, cytokine release syndrome, or anaphylactic reactions. The Investigator is responsible for the detection and documentation of AEs, and assessment of severity and causality. ; ; Abnormal laboratory findings (e.g., clinical chemistry, hematology, urinalysis, complement, cytokines) or other abnormal assessments (e.g., ECGs and vital signs) that are judged by the Investigator as clinically significant will be recorded as AEs. ; ; Discontinuation: The Investigator is responsible for determining if any AE or laboratory abnormality indicates that continued participation in the study is not in the best interest of the subject. SECONDARY OUTCOME: ARB‐1740 pharmacokinetic parameters including maximum observed plasma concentration (Cmax), time of maximum observed plasma concentration (Tmax), and area under the plasma concentration‐time curve from the start of infusion to the last measurable concentration (AUC0‐t) assessed by plasma analysis. Composite Secondary Outcome: The frequency and severity of treatment‐emergent AEs, discontinuations due to AEs, and laboratory abnormalities, by cohort, in HBV‐DNA Positive (+) subjects, assessed through continuous monitoring by the Investigator. ; ; Possible AEs may include infusion related reactions, cytokine release syndrome, or anaphylactic reactions. The Investigator is responsible for the detection and documentation of AEs, and assessment of severity and causality. ; ; INCLUSION CRITERIA: 1. Chronic HBV infection as documented at screening by either: i. Positive HBsAg or HBeAg or HBV‐DNA at least 6 months prior to screening; OR ii. Historical liver biopsy consistent with chronic HBV infection at screening. 2. Quantitiative HBsAg greater than or equal to 1000 IU/mL at the Screening Visit. 3. For Cohorts 2 and 3: Subjects currently receiving entecavir and/or tenofovir for greater than or equal to 12 months and HBV‐DNA undetectable. ; Abnormal laboratory findings (e.g., clinical chemistry, hematology, urinalysis, complement, cytokines) or other abnormal assessments (e.g., ECGs and vital signs) that are judged by the Investigator as clinically significant will be recorded as AEs. ; Discontinuation: The Investigator is responsible for determining if any AE or laboratory abnormality indicates that continued participation in the study is not in the best interest of the subject. HBV surface antigen (HBsAg) levels in virally suppressed [HBV‐DNA(‐)] subjects, assessed by blood tests.