Study of ARO-HBV in Normal Adult Volunteers and Patients With Hepatitis B Virus (HBV)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-HBV in healthy adult volunteers and participants with hepatitis B virus (HBV).

Official Title
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A Phase 1/2a Single Dose-Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetic Effects of ARO-HBV in Normal Adult Volunteers and Multiple Escalating Doses Evaluating Safety, Tolerability and Pharmacodynamic Effects in HBV Patients

Conditions
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Hepatitis B

Intervention / Treatment
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* Drug: ARO-HBV Injection
* Other: Sterile Normal Saline (0.9% NaCl)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Parts A & B: Women of childbearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use contraception. Willing to provide written informed consent and comply with study requirements Additional Inclusion Criteria for Part B: Diagnosis of chronic HBV infection HbsAg at screening > or = 50 IU/mL Liver Elastography score < or = 10.5 Exclusion Criteria: Clinically significant health concerns (with the exception of HBV for Patients in Part B) Abnormal for any clinical safety laboratory result considered clinically significant Regular use of alcohol within 1 month prior to screening Recent use of illicit drugs Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study NOTE: additional inclusion/exclusion criteria may apply, per protocol

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ARO-HBV Injection<br> | Drug: ARO-HBV Injection<br>* Single or multiple doses of ARO-HBV Injection by subcutaneous (sc) injection<br>|
| Placebo Comparator: Placebo<br> | Other: Sterile Normal Saline (0.9% NaCl)<br>* Calculated volume to match active comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) Possibly or Probably Related to Treatment |  | Up to 203 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of ARO-HBV: Maximum Observed Plasma Concentration (Cmax) |  | Part A (single-ascending dose [SAD] phase) only: up to 48 hours post-dose | 
| PK of ARO-HBV: Time to Maximum Plasma Concentration (Tmax) |  | Part A (SAD phase) only: up to 48 hours post-dose | 
| PK of ARO-HBV: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) |  | Part A (SAD phase) only: up to 48 hours post-dose | 
| PK of ARO-HBV: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) |  | Part A (SAD phase) only: up to 48 hours post-dose | 
| PK of ARO-HBV: Terminal Elimination Half-Life (t½) |  | Part A (SAD phase) only: up to 48 hours post-dose | 
| Reduction of HBV Surface Antigen (HBsAg) from Day 1 Pre-Dose Baseline to Post-Dose Nadir in Participants Chronically Infected With HBV |  | Part B (multiple-ascending dose [MAD] phase) only: up to 113 days |