Conditions: Hepatitis B
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 47
Healthy volunteers: yes

Brief 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.

Detailed description:
Phase 1a/1b multicenter dose-escalation study of ARC-521 Injection in normal healthy volunteers and patients with CHB. Eligible participants who have signed an Ethics Committee (EC)/Institutional Review Board (IRB) approved informed consent form and have met all of the protocol eligibility criteria.

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), concomitant medications/therapies assessment, electrocardiograms (ECGs), telemetry \[NHVs only\], measures of hepatic fibrosis \[CHBs only\], blood sample collection for hematology, coagulation, chemistry, Pharmacokinetics (PK) \[NHVs only\], metabolic analysis \[NHVs only\], exploratory Pharmacodynamic (PD) measures, urinalysis, hepatitis B virus (HBV) serology, immunogenicity, 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. Prior to enrollment there is a 60 day screening period.

Arms:
arm 1: NHV participants administered a single dose of ARC-521 Injection at a dose of 0.6 mg/kg. arm 2: NHV participants administered a single dose of ARC-521 Injection at a dose of 1 mg/kg. arm 3: NHV participants administered a single dose of ARC-521 Injection at a dose of 2 mg/kg. arm 4: NHV participants administered a single dose of ARC-521 Injection at a dose of 4 mg/kg. arm 5: NHV participants administered a single dose of ARC-521 Injection at a dose of 5 mg/kg. arm 6: NHV participants administered a single dose of ARC-521 Injection at a dose of 6 mg/kg. arm 7: NHV participants administered 0.9% normal saline to match ARC-521 Injection at doses of 0.6, 1, 2, 4, 5 and 6 mg/kg. arm 8: Treatment-naive participants with CHB administered 3 doses of ARC-521 Injection at 2 mg/kg once every 4 weeks. Participants are treatment-naive if they have not been on continual nucleoside analog (NUC) therapy (any NUC) for at least 6 months prior to screening (or have never been on NUCs). arm 9: Treatment-naive participants with CHB administered 3 doses of ARC-521 Injection at 4 mg/kg once every 4 weeks. Participants are treatment-naive if they have not been on continual NUC therapy (any NUC) for at least 6 months prior to screening (or have never been on NUCs). arm 10: Participants with CHB currently on NUCs (entecavir or tenofovir for at least 6 months) administered 3 doses of ARC-521 Injection at 2 mg/kg once every 4 weeks. arm 11: Participants with CHB currently on NUCs (entecavir or tenofovir for at least 6 months) administered 3 doses of ARC-521 Injection at 4 mg/kg once every 4 weeks.

Interventions: intervention 1: ARC-521 Injection intervention 2: Placebo intervention 3: antihistamine intervention 4: acetaminophen intervention 5: entecavir intervention 6: tenofovir
Intervention descriptions: intervention 1: None intervention 2: 0.9% normal saline intervention 3: 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. intervention 4: 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). intervention 5: Participants take entecavir OR tenofovir daily throughout the study. intervention 6: Participants take entecavir OR tenofovir daily throughout the study.

Protocol document: