Study Stopped
Company decision to discontinue trial
A Multicenter Study to Determine the Depth and Duration of Hepatitis B Surface Antigen (HBsAg) Reduction After Single or Multiple Doses of ARC-520, in Combination With Entecavir in Patients With Chronic Hepatitis B Virus (HBV) Infection
A Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study to Determine the Depth and Duration of Hepatitis B Surface Antigen (HBsAg) Reduction After a Single Intravenous Dose of ARC-520 in Combination With Entecavir in Patients With Chronic Hepatitis B Virus (HBV) Infection, Followed by a Two-dose Open-label Cohort and Three Open-label Single-dose Cohorts in Treatment Naïve Patients, Including a Multi-dose Open-label Extension at a Single Center
1 other identifier
interventional
58
1 country
2
Brief Summary
The purpose of this study is to determine whether ARC-520 in combination with entecavir is effective in the treatment of patients with chronic HBV Infection.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Mar 2014
Typical duration for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 13, 2014
CompletedFirst Posted
Study publicly available on registry
February 19, 2014
CompletedStudy Start
First participant enrolled
March 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2017
CompletedResults Posted
Study results publicly available
July 5, 2019
CompletedJanuary 13, 2026
December 1, 2025
2.8 years
February 13, 2014
January 10, 2018
December 19, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG)
Baseline, through Day 85 (Cohorts 1-7) and through 24 weeks post-last dose (last dose: Day 85 Cohort 9; Day 253 Cohort 10)
Secondary Outcomes (12)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
through Day 85 (Cohorts 1-7) and through 24 weeks post-last dose (last dose: Day 85 Cohort 9; Day 225 Cohort 10)
Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85
Baseline, Day 29, Day 85
Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7
Baseline, Days 1, 2, 3, 8, 15, 22, 29
Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24), Cohorts 1-5
Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose
Pharmacokinetics of ARC-520 of ARC-520 Product Constituents AD0009 and AD0010: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast), Cohorts 1-5
Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose
- +7 more secondary outcomes
Study Arms (13)
ARC-520 Cohort 1
EXPERIMENTALa single intravenous (IV) dose of double-blind ARC-520 Injection 1.0 mg/kg in combination with entecavir administered to participants with HBeAg-negative immune active chronic HBV infection
ARC-520 Cohort 2
PLACEBO COMPARATORa single IV dose of double-blind ARC-520 Injection 2.0 mg/kg in combination with entecavir administered to participants with HBeAg-negative immune active chronic HBV infection
ARC-520 Cohort 3
EXPERIMENTALa single IV dose of double-blind ARC-520 Injection 3.0 mg/kg in combination with entecavir administered to participants with HBeAg-negative immune active chronic HBV infection
ARC-520 Cohort 4
EXPERIMENTALa single IV dose of double-blind ARC-520 Injection 4.0 mg/kg in combination with entecavir administered to participants with HBeAg-negative immune active chronic HBV infection
ARC-520 Cohort 5
EXPERIMENTALa single IV dose of double-blind ARC-520 Injection 4.0 mg/kg in combination with entecavir administered to participants with HBeAg-positive immune active chronic HBV infection
Placebo Normal Saline Cohorts 1-5
EXPERIMENTALa single IV dose of double-blind normal saline in combination with entecavir administered to participants with HBeAg-negative or -positive immune active chronic HBV infection
ARC-520 Cohort 6
EXPERIMENTALtwo IV doses of open-label ARC-520 2.0 mg/kg administered to participants with HBeAg-positive immune active chronic HBV
ARC-520 Cohort 7
EXPERIMENTALa single IV dose of open-label ARC-520 4.0 mg/kg administered to treatment-naïve, HBeAg-negative or -positive participants with chronic hepatitis B (CHB)
ARC-520 Cohort 8
EXPERIMENTALopen-label multi-dose extension cohort: multiple IV doses of open-label ARC-520 (4.0 mg/kg every \[Q\]4 weeks) administered to HBeAg-negative participants with CHB receiving chronic entecavir therapy who completed Cohorts 1 through 4
ARC-520 Cohort 9
EXPERIMENTALopen-label multi-dose extension cohort: multiple IV doses of open-label ARC-520 (4.0 mg/kg Q6 weeks or Q8 weeks) administered to HBeAg-positive participants with CHB receiving chronic entecavir therapy who completed Cohorts 5 or 6
ARC-520 Cohort 10
EXPERIMENTALopen-label multi-dose extension cohort: multiple IV doses of open-label ARC-520 (4.0 mg/kg Q4 weeks) administered to a mixed cohort (HBeAg-negative and -positive participants) who were naïve (within the last 6 months) to entecavir treatment and completed Cohort 7
ARC-520 Cohort 11
EXPERIMENTALa single IV dose of open-label ARC-520 5.0 mg/kg administered to treatment-naïve, HBeAg-positive participants with CHB
ARC-520 Cohort 12
EXPERIMENTALa single IV dose of open-label ARC-520 6.0 mg/kg administered to treatment-naïve, HBeAg-positive participants with CHB
Interventions
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.
Eligibility Criteria
You may qualify if:
- Diagnosis of HBeAg negative and immune active chronic HBV infection (Cohorts 1-4, 8)
- Diagnosis of HBeAg positive and immune active chronic HBV infection (Cohorts 5-6, 9)
- Diagnosis of HBeAg negative or HBeAg positive and immune active or tolerant chronic HBV infection (Cohorts 7, 10, 11 \& 12)
- Patients with \> 6 months of continuous, 0.5 mg/day oral entecavir, and a willingness to continue taking entecavir throughout the study (Cohorts 1-6, 8-9).
- Patients naive to entecavir (never on entecavir or on entecavir \<30 days prior to screening) and a willingness to take entecavir and willingness to continue taking entecavir throughout the study (Cohorts 7, 11 \& 12).
You may not qualify if:
- Female patients that have a positive pregnancy test or are lactating.
- Acute signs of hepatitis/other infection (eg, moderate fever, jaundice, nausea, vomiting, and abdominal pain) evident within 4 weeks of screening and/or at the screening examination.
- Patients with antiviral therapy other than entecavir within 3 months of screening or prior treatment with interferon or a toll receptor agonist in the last 5 years.
- Use within the last 6 months or an anticipated requirement for anticoagulants, corticosteroids, immunomodulators, or immunosuppressants.
- Has any history of autoimmune disease especially autoimmune hepatitis.
- Has human immunodeficiency virus (HIV) infection, as shown by the presence of anti-HIV antibody (sero-positive).
- Is sero-positive for hepatitis C virus (HCV), and/or a history of delta virus hepatitis.
- Has a history of allergy to bee venom or history of hypersensitivity reaction requiring an emergency visit to a physician or hospital and/or requirement for treatment with steroids and/or epinephrine.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Arrowhead Pharmaceuticalslead
- ICON Clinical Researchcollaborator
Study Sites (2)
Research Site 1
Pokfulam, Hong Kong
Research Site 2
Shatin, Hong Kong
Related Publications (1)
Yuen MF, Wong DK, Schluep T, Lai CL, Ferrari C, Locarnini S, Lo RC, Gish RG, Hamilton J, Wooddell CI, Mak LY, Given BD. Long-term serological, virological and histological responses to RNA inhibition by ARC-520 in Chinese chronic hepatitis B patients on entecavir treatment. Gut. 2022 Apr;71(4):789-797. doi: 10.1136/gutjnl-2020-323445. Epub 2021 Mar 12.
PMID: 33712437DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The ARC-520 Injection development program was terminated early for regulatory and business reasons secondary to findings occurring in a non-clinical toxicology study. Program termination was not due to safety findings in humans.
Results Point of Contact
- Title
- Chief Operating Officer
- Organization
- Arrowhead Pharmaceuticals, Inc.
Study Officials
- STUDY CHAIR
Bruce Given, MD
Arrowhead Pharmaceuticals, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 13, 2014
First Posted
February 19, 2014
Study Start
March 1, 2014
Primary Completion
January 1, 2017
Study Completion
January 1, 2017
Last Updated
January 13, 2026
Results First Posted
July 5, 2019
Record last verified: 2025-12