Study of ARC-520 With or Without Other Drugs Used in the Treatment of Chronic Chronic Hepatitis B Virus (HBV)

NCT02577029 | Terminated Phase 2 Results

• 2 other identifiers: Heparc-20082015-005499-46
• Study Type: interventional
• Target: 79
• Locations: 8 countries
• Sites: 33

Brief Summary

Patients with chronic HBV infection will receive either ARC-520 alone or ARC-520 in combination with other treatments such as entecavir (ENT) or tenofovir (TDF) and/or pegylated interferon (PEG IFN) alpha 2a therapy, and be evaluated for safety and efficacy.

Conditions

Hepatitis B; Hepatitis D

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving a 1-log Reduction in Hepatitis B Surface Antigen (HBsAg) at Week 60 Compared to Baseline

  The percentage of participants with chronic HBV achieving a 1-log reduction in HBsAg compared to baseline (mean of pre-dose values) at Week 60 after completion of 48 weeks of ARC-520 Injection.

  Baseline, Week 60

Secondary Outcomes (11)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Considered Possibly or Probably Related to Treatment

  From first dose of study drug up to 36 weeks of treatment, plus up to 48 weeks of follow-up

• Percentage of Participants With HBsAg Loss (Based on Qualitative Assay) Over Time

  Weeks 52, 60, 72 and 96

• Percentage of Participants Achieving a 1-log Reduction in HBsAg and Achieving an HBsAg Level < 100 IU/L Over Time

  Weeks 52, 60, 72 and 96

• Time to HBsAg Loss

  Baseline through Week 96

• Time to Anti-HBs (Antibody to Hepatitis B Surface Antigen) Seroconversion

  Baseline through Week 96

Study Arms (8)

Cohort 1

EXPERIMENTAL

Treatment-naïve, hepatitis B "e" antigen (HBeAg)-positive participants with chronic hepatitis B (CHB) of any genotype administered ARC-520 (2 mg/kg intravenous \[IV\]) every 4 weeks for 48 weeks (13 doses).

Drug: ARC-520; Drug: antihistamine

Cohort 2

EXPERIMENTAL

Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered peginterferon (PEG IFN) alpha 2a for 48 weeks starting Day 87.

Drug: ARC-520; Drug: entecavir; Biological: pegylated interferon alpha 2a; Drug: tenofovir disoproxil; Drug: antihistamine

Cohort 3

EXPERIMENTAL

Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.

Drug: ARC-520; Drug: entecavir; Biological: pegylated interferon alpha 2a; Drug: tenofovir disoproxil; Drug: antihistamine

Cohort 4

EXPERIMENTAL

Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.

Drug: ARC-520; Drug: entecavir; Biological: pegylated interferon alpha 2a; Drug: tenofovir disoproxil; Drug: antihistamine

Cohort 5

EXPERIMENTAL

Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.

Drug: ARC-520; Drug: entecavir; Biological: pegylated interferon alpha 2a; Drug: tenofovir disoproxil; Drug: antihistamine

Cohort 6

EXPERIMENTAL

Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.

Drug: ARC-520; Drug: entecavir; Biological: pegylated interferon alpha 2a; Drug: tenofovir disoproxil; Drug: antihistamine

Cohort 7

EXPERIMENTAL

Treatment-naïve, HBeAg-negative or HBeAg-positive participants with hepatitis delta virus (HDV) administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.

Drug: ARC-520; Biological: pegylated interferon alpha 2a; Drug: antihistamine

Cohort 8

EXPERIMENTAL

Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).

Drug: ARC-520; Drug: antihistamine

Interventions

ARC-520 DRUG

ARC-520 will be administered intravenously concomitantly with 0.9% normal saline using an infusion rate of 0.4 mL/min (24 mL/hour) for study treatment and 200 mL/hr for saline.

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6; Cohort 7; Cohort 8

entecavir DRUG

0.5 mg once daily; oral

Also known as: Baraclude

Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6

pegylated interferon alpha 2a BIOLOGICAL

180 mcg; subcutaneous injection once weekly

Also known as: Peginterferon, Pegasys

Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6; Cohort 7

tenofovir disoproxil DRUG

300 mg once daily; oral

Also known as: Viread

Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6

antihistamine DRUG

All participants will be pre-treated with an oral antihistamine selected by the investigator from the list of approved antihistamines that is available in that country. Acceptable antihistamines are: diphenhydramine 50 mg p.o., chlorpheniramine 8 mg p.o., hydroxyzine 50 mg p.o., or cetirizine 10 mg p.o.

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6; Cohort 7; Cohort 8

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
• Diagnosis of HBeAg negative or positive chronic HBV infection.
• Must be HBsAg (+) during screening.
• Must be treatment naïve: never on PEG IFN alpha 2a and/or ETV or TDF; and
• Have not used nucleoside/nucleotide analogs (NUCs) within the last 2 years prior to dosing on Day 1
• 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 severe infections within 4 weeks of screening
• Use within the last 14 days or anticipated requirement for anticoagulants, systemic 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, over-the-counter (OTC) and prescription pain medication or hormonal contraceptives
• History of poorly controlled autoimmune disease or any history of autoimmune hepatitis
• History of heterozygous or homozygous familial hypercholesterolemia.
• Human immunodeficiency virus (HIV) infection
• Is sero-positive for Hepatitis C Virus (HCV), or has a history of delta virus hepatitis (except for cohort in which delta virus infection is acceptable)
• Has hypertension: blood pressure \> 170/100 mmHg; well-controlled blood pressure on hypertensive medication allowed
• History of cardiac rhythm disturbances
• Family history of 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
• History of malignancy, except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer
• Has had major surgery within 1 month of screening
• Regular use of alcohol within 6 months prior to screening (ie, more than 14 units of alcohol per week)

Sponsors & Collaborators

• Arrowhead Pharmaceuticals: lead

Study Sites (33)

Research Site 3

Camperdown, New South Wales, 2050, Australia

Location

Research Site 8

Concord, New South Wales, 2139, Australia

Location

Research Site 5

Darlinghurst, New South Wales, 2010, Australia

Location

Research Site 1

Westmead, New South Wales, 2145, Australia

Location

Research Site 9

Adelaide, South Australia, 5000, Australia

Location

Research Site 6

Clayton, Victoria, 3168, Australia

Location

Research Site 4

Fitzroy, Victoria, 3065, Australia

Location

Research Site 2

Parkville, Victoria, 3052, Australia

Location

Research Site 7

Nedlands, Washington, 6009, Australia

Location

Research Site 13

Pleven, 5800, Bulgaria

Location

Research Site 10

Sofia, 1431, Bulgaria

Location

Research Site 11

Sofia, 1463, Bulgaria

Location

Research Site 12

Varna, 9020, Bulgaria

Location

Research Site 14

Hong Kong, China

Location

Research Site 25

Chisinau, MD-2004, Moldova

Location

Research Site 23

Papatoetoe, Aukland, 2025, New Zealand

Location

Research Site 24

Dunedin, Otago-Southland, New Zealand

Location

Research Site 21

Auckland, 1010, New Zealand

Location

Research Site 17

Busan, 49241, South Korea

Location

Research Site 19

Busan, South Korea

Location

Research Site 16

Daegu, 41944, South Korea

Location

Research Site 18

Seoul, 3080, South Korea

Location

Research Site 15

Seoul, 6273, South Korea

Location

Research Site 20

Seoul, South Korea

Location

Research Site 27

Douliu, Yunlin County, 640, Taiwan

Location

Research Site 26

Changhua, 500, Taiwan

Location

Research Site 28

Kaohsiung City, 807, Taiwan

Location

Research Site 29

Bangkok, 10330, Thailand

Location

Research Site 30

Bangkok, 10400, Thailand

Location

Research Site 32

Bangkok, 10400, Thailand

Location

Research Site 33

Chiang Mai, 50200, Thailand

Location

Research Site 31

Khon Kaen, 40002, Thailand

Location

Research Site 34

Pathum Thani, 12120, Thailand

Location

MeSH Terms

Conditions

Hepatitis B; Hepatitis D

Interventions

ARC-520; entecavir; peginterferon alfa-2a; 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; RNA Virus Infections

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2015
• First Posted: October 15, 2015
• Study Start: December 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 13, 2026
• Results First Posted: April 12, 2019

Record last verified: 2025-12

Locations

NZ (3); KR (6); CN (1); TW (3); BU (4); TH (6); AU (9); MO (1)