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

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

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).

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Other: Sterile Normal Saline (0.9% NaCl); Drug: ARO-HBV Injection

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Melbourne, Victoria, Australia, 3065
      • St. Vincent's Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Research
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Auckland Clinical Studies Limited
    • Papatoetoe, Auckland, New Zealand, 2025
      • Middlemore Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Publications and helpful links

General Publications

• Gane E, Yuen MF, Kakuda TN, Ogawa T, Takahashi Y, Goeyvaerts N, Lonjon-Domanec I, Vaughan T, Schluep T, Hamilton J, Njumbe Ediage E, Hillewaert V, Snoeys J, Lenz O, Talloen W, Biermer M. JNJ-73763989 pharmacokinetics and safety: Liver-targeted siRNAs against hepatitis B virus, in Japanese and non-Japanese healthy adults, and combined with JNJ-56136379 and a nucleos(t)ide analogue in patients with chronic hepatitis B. Antivir Ther. 2022 Jun;27(3):13596535221093856. doi: 10.1177/13596535221093856.
• Yuen MF, Locarnini S, Lim TH, Strasser SI, Sievert W, Cheng W, Thompson AJ, Given BD, Schluep T, Hamilton J, Biermer M, Kalmeijer R, Beumont M, Lenz O, De Ridder F, Cloherty G, Ka-Ho Wong D, Schwabe C, Jackson K, Lai CL, Gish RG, Gane E. Combination treatments including the small-interfering RNA JNJ-3989 induce rapid and sometimes prolonged viral responses in patients with CHB. J Hepatol. 2022 Nov;77(5):1287-1298. doi: 10.1016/j.jhep.2022.07.010. Epub 2022 Jul 20.

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2018
• Primary Completion (Actual): April 23, 2020
• Study Completion (Actual): April 23, 2020

Study Registration Dates

• First Submitted: December 4, 2017
• First Submitted That Met QC Criteria: December 4, 2017
• First Posted (Actual): December 8, 2017

Study Record Updates

• Last Update Posted (Actual): April 26, 2021
• Last Update Submitted That Met QC Criteria: April 22, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A
• Other Study ID Numbers: AROHBV1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes