A Multi-dose Study of ARC-520 in Patients With Hepatitis B 'e' Antigen (HBeAg) Negative, Chronic Hepatitis B Virus (HBV) Infection

NCT02604199 | Terminated Phase 2 Results DMC

• 2 other identifiers: Heparc-20022014-004145-27
• Study Type: interventional
• Target: 58
• Locations: 3 countries
• Sites: 16

Brief Summary

Patients with chronic HBV infection will receive either ARC-520 or placebo in combination with entecavir or tenofovir, and be evaluated for safety and efficacy.

Conditions

Hepatitis B

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 113

  Change From Baseline in log qHBsAg at Day 113 in response to multiple doses of ARC-520 versus placebo, using a a mixed effect model for repeated measures (MMRM). Includes parameter baseline as a continuous covariate, and treatment and visit as fixed factors, interaction of treatment and visit, and interaction of parameter baseline and visit.

  Baseline, Day 113

Secondary Outcomes (10)

• Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time

  Baseline, Day 15, 29, 43, 57, 71, 85, 99

• Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs

  Through Day 169

• Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24)

  Through 48 hours post-dosing on Day 1 and Day 85

• Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast)

  Through 48 hours post-dosing on Day 1 and Day 85

• Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf)

  Through 48 hours post-dosing on Day 1 and Day 85

Study Arms (4)

PBO Low Dose

PLACEBO COMPARATOR

0.9% normal saline, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period

Other: placebo; Drug: entecavir; Drug: tenofovir; Drug: antihistamine

PBO High Dose

PLACEBO COMPARATOR

0.9% normal saline, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period

Other: placebo; Drug: entecavir; Drug: tenofovir; Drug: antihistamine

ARC-520 Injection 1 mg/kg

EXPERIMENTAL

Intravenous ARC-520 at 1.0 mg/kg, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period

Drug: ARC-520 Injection; Drug: entecavir; Drug: tenofovir; Drug: antihistamine

ARC-520 Injection 2 mg/kg

EXPERIMENTAL

Intravenous ARC-520 at 2.0 mg/kg, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period

Drug: ARC-520 Injection; Drug: entecavir; Drug: tenofovir; Drug: antihistamine

Interventions

ARC-520 Injection DRUG

ARC-520 Injection was administered concomitantly, IV with 0.9% normal saline using an infusion rate of 0.4 mL/min for study treatment and 3.6 mL/min for saline.

ARC-520 Injection 1 mg/kg; ARC-520 Injection 2 mg/kg

placebo OTHER

Placebo was administered concomitantly, IV with 0.9% normal saline using an infusion rate of 0.4 mL/min for study treatment and 3.6 mL/min for saline.

PBO High Dose; PBO Low Dose

entecavir DRUG

All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.

ARC-520 Injection 1 mg/kg; ARC-520 Injection 2 mg/kg; PBO High Dose; PBO Low Dose

tenofovir DRUG

All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.

ARC-520 Injection 1 mg/kg; ARC-520 Injection 2 mg/kg; PBO High Dose; PBO Low Dose

antihistamine DRUG

All participants will be pretreated with an oral antihistamine, administered 2 hours (±30 minutes) pre-dose. The antihistamine used should in general be an H1\>H2 receptor blocker and would include diphenhydramine 50 mg, cetirizine 10 mg, chlorpheniramine 8 mg or hydroxyzine 50 mg. The Investigator is free to choose any of these antihistamines available locally and consistent with their country's Marketing Authorisation.

ARC-520 Injection 1 mg/kg; ARC-520 Injection 2 mg/kg; PBO High Dose; PBO Low Dose

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, 18 to 75 years of age
• Written informed consent
• No clinically significant abnormalities at screening/pre-dose 12-lead ECG assessment
• No new abnormal finding of clinical relevance at the screening evaluation.
• Diagnosis of HBeAg negative, immune active, chronic HBV infection
• \> 2 months of continuous treatment with daily, oral entecavir or tenofovir
• Willingness to continue taking entecavir or tenofovir throughout the study.
• Must use 2 effective methods of contraception (double barrier contraception or hormonal contraceptive along with a barrier contraceptive) (both male and female partners)

You may not qualify if:

• Pregnant or lactating
• Acute signs of hepatitis/other infection within 4 weeks of screening
• Antiviral therapy other than entecavir or tenofovir within 3 months of screening
• Prior treatment with interferon in the last 3 years.
• Use within the last 6 months or anticipated requirement for anticoagulants, corticosteroids, immunomodulators, or immunosuppressants.
• Use of prescription medication within 14 days prior to treatment administration except: topical products without systemic absorption, statins (except rosuvastatin), hypertension medications, or hormonal contraceptives.
• Depot injection or implant of any drug within 3 months prior to treatment administration, except injectable/implantable birth control.
• Diagnosis of diabetes mellitus.
• History of autoimmune disease especially autoimmune hepatitis.
• Human immunodeficiency virus (HIV) infection.
• Sero-positive for Hepatitis C Virus (HCV), and/or a history of delta virus hepatitis.
• Hypertension defined as blood pressure \> 150/100 mmHg
• History of cardiac rhythm disturbances
• Family history or congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death
• Symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease within 6 months prior to study entry.

Sponsors & Collaborators

• Arrowhead Pharmaceuticals: lead

Study Sites (16)

Research Site 1

Hong Kong, 999077, China

Location

Research Site 2

Hong Kong, China

Location

Research Site 11

Frankfurt, 60590, Germany

Location

Research Site 9

Hamburg, 20099, Germany

Location

Research Site 8

Hanover, 30625, Germany

Location

Research Site 10

Leipzig, 04103, Germany

Location

Research Site 4

Leipzig, 4103, Germany

Location

Research Site 5

München, 81377, Germany

Location

Research Site 3

Tübingen, 72076, Germany

Location

Research Site 6

Ulm, 89081, Germany

Location

Research Site 7

Würzburg, 97080, Germany

Location

Research Site 13

Busan, 602-739, South Korea

Location

Research Site 15

Incheon, 405-760, South Korea

Location

Research Site 14

Seoul, 110-744, South Korea

Location

Research Site 16

Seoul, 120-752, South Korea

Location

Research Site 12

Yangsan-si Gyeongnam, 626-770, South Korea

Location

MeSH Terms

Conditions

Hepatitis B

Interventions

ARC-520; entecavir; Tenofovir; Histamine Antagonists

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs

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.

626-304-3400

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2015
• First Posted: November 13, 2015
• Study Start: September 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: January 13, 2026
• Results First Posted: April 16, 2019

Record last verified: 2025-12

Locations

CN (2); KR (5); DE (9)