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

Phase 1

Completed

• Conditions: Hepatitis B
• Interventions: Drug: ARO-HBV; Other: Sterile Normal Saline (0.9% NaCl); Drug: JNJ-56136379

• Registration Number: NCT03365947
• Lead Sponsor: Arrowhead Pharmaceuticals

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-12-04
• Study First Submitted QC: 2017-12-04
• Study First Posted: 2017-12-08
• Study Start: 2018-03-27
• Primary Completion: 2020-04-23
• Study Completion: 2020-04-23
• Disposition First Submitted: 2021-04-22
• Results First Submitted: 2024-04-11
• Status Verified: 2024-05
• Results First Submitted QC: 2024-05-06
• Last Update Submitted: 2024-05-06
• Results First Posted: 2024-06-04
• Disposition First Posted: 2024-06-04
• Last Update Posted: 2024-06-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 114

Inclusion Criteria

Not provided

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Possibly or Probably Related to Treatment	NHV participants: up to Day 29 (± 2 days); CHB participants: Day 113 (± 2 days)	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.

Secondary Outcome Measures

Name	Time	Method
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: 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
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: 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

Trial Locations

Locations (7)

Auckland Clinical Studies Limited; 🇳🇿 Grafton, Auckland, New Zealand

Middlemore Clinical Trials; 🇳🇿 Papatoetoe, Auckland, New Zealand

Linear Research; 🇦🇺 Nedlands, Western Australia, Australia

Royal Prince Alfred Hospital; 🇦🇺 Camperdown, New South Wales, Australia

Monash Medical Centre; 🇦🇺 Clayton, Victoria, Australia

St. Vincent's Hospital; 🇦🇺 Melbourne, Victoria, Australia

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong