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: Drug: ARO-HBV; Other: Sterile Normal Saline (0.9% NaCl); Drug: JNJ-56136379

• 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
      • Research Site 5
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Research Site 4
    • Melbourne, Victoria, Australia, 3065
      • Research Site 3
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Research Site 6
• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site 7
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Research Site 1
    • Papatoetoe, Auckland, New Zealand, 2025
      • Research Site 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

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
• Hepatitis B surface antigen (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

19

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARO-HBV 35 mg; Single dose of ARO-HBV 35 mg subcutaneous (sc) injection in normal healthy volunteers	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 100 mg; Single dose of ARO-HBV 100 mg sc injection in normal healthy volunteers	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 200 mg; Single dose of ARO-HBV 200 mg sc injection in normal healthy volunteers	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 300 mg; Single dose of ARO-HBV 300 mg sc injection in normal healthy volunteers	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 400 mg; Single dose of ARO-HBV 400 mg sc injection in normal healthy volunteers	Drug: ARO-HBV; sc injection
Placebo Comparator: Placebo; Sterile normal saline (0.9% NaCl) sc injection in normal healthy volunteers	Other: Sterile Normal Saline (0.9% NaCl); sc injection
Experimental: ARO-HBV 25 mg, Q28D; ARO-HBV 25 mg sc injection every 28 days (Q28D) in participants with chronic hepatitis B	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 50 mg Q28D; ARO-HBV 50 mg sc injection Q28D in participants with chronic hepatitis B	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 100 mg Q28D; ARO-HBV 100 mg sc injection Q28D in participants with chronic hepatitis B	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 200 mg Q28D; ARO-HBV 200 mg sc injection Q28D in participants with chronic hepatitis B	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 300 mg Q28D; ARO-HBV 300 mg sc injection Q28D in participants with chronic hepatitis B	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 400 mg Q28D; ARO-HBV 400 mg sc injection Q28D in participants with chronic hepatitis B	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 100 mg Q14D; ARO-HBV 100 mg sc injection every 14 days (Q14D) in participants with chronic hepatitis B	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 100 mg Q7D; ARO-HBV 100 mg sc injection every 7 days (Q7D) in participants with chronic hepatitis B	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 300 mg, Q28D, HBeAg+/ Trt Naïve; ARO-HBV 300 mg sc injection Q28D in hepatitis B e antigen positive/treatment naïve (HBeAg+/Trt Naïve) participants with chronic hepatitis B	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 300 mg, Q28D, HBeAg+/ NUC; ARO-HBV 300 mg sc injection Q28D in HBeAg+/nucleotide or nucleoside analog treated (HBeAg+/NUC) participants with chronic hepatitis B	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 200 mg, Q7D; ARO-HBV 200 mg sc injection Q7D in participants with chronic hepatitis B	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 300 mg, Q7D; ARO-HBV 300 mg sc injection Q7D in participants with chronic hepatitis B	Drug: ARO-HBV; sc injection
Experimental: ARO-HBV 200 mg Q28D + JNJ-56136379 250 mg; ARO-HBV 200 mg sc injection Q28D plus JNJ-56136379 250 mg in participants with chronic hepatitis B	Drug: ARO-HBV; sc injection; Drug: JNJ-56136379; oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Possibly or Probably Related to Treatment	An adverse event (AE) is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. TEAEs were defined as AEs with onset after administration of the study drug, or when a preexisting medical condition increases in severity or frequency after study drug administration. Assessment of causality utilized 3 possible categories: not related, possibly related and probably related.	NHV participants: up to Day 29 (± 2 days); CHB participants: Day 113 (± 2 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Part A, Pharmacokinetics (PK) of ARO-HBV Analytes: Maximum Observed Plasma Concentration (Cmax)	Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
Part A, PK of ARO-HBV Analytes : Time to Maximum Plasma Concentration (Tmax)	Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
Part A, PK of ARO-HBV Analytes: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)	Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 hours post-dose
Part A, PK of ARO-HBV Analytes: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)	Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
Part A, PK of ARO-HBV Analytes: Area Under the Plasma Concentration Versus Time Curve From Zero to the Time of the Last Quantifiable Concentration (AUC0-t)	Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
Part A, PK of ARO-HBV Analytes: Terminal Elimination Half-Life (t½)	Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
Part A, PK of ARO-HBV Analytes: Dose-Normalized AUC0-24	Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 hours post-dose
Part A, PK of ARO-HBV Analytes: Dose-Normalized AUC0-t	Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
Part A, PK of ARO-HBV Analytes: Dose-Normalized Cmax	Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose
Change From Baseline in 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 (Estimated): October 22, 2025
• Last Update Submitted That Met QC Criteria: October 7, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis; Hepatitis B; Anti-Infective Agents; Antiviral Agents; JNJ-56136379
• 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