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

NCT ID: NCT02577029

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 79 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2016-12-31

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.

Detailed Description

This is a multicenter, open-label study of ARC-520 based treatment regimens administered to patients with HBeAg positive or HBeAg negative immune active chronic Hepatitis B Virus (HBV) infection of various genotypes, or patients with Hepatitis D Virus (HDV). Eligible patients naive to previous treatment, and who have signed an Ethics Committee - approved informed consent, will be enrolled and will receive ARC-520 alone or ARC-520 plus additional treatments such as entecavir (ETV) or tenofovir (TDF) and/or pegylated interferon alpha 2a (PEG IFN) therapy. The study may initially involve up to a total of 96 eligible chronic HBV and HDV infected patients. Patients in all cohorts will receive a total of 13 doses of ARC-520 at 2mg/kg or 4 mg/kg. Patients will undergo the following evaluations at regular intervals during the study: medical history, physical examinations, vital sign measurements (blood pressure, heart rate, respiratory rate, and temperature), weight, adverse events assessment (AEs), 12-lead ECGs, liver fibrosis testing, concomitant medication assessment, blood sample collection for hematology, coagulation, chemistry, exploratory Pharmacodynamic (PD) measures, urinalysis, HBV serology, cytokines, Follicle Stimulating Hormone (FSH) testing (post-menopausal females) and pregnancy testing for females of childbearing potential. Clinically significant changes including AEs will be followed until resolution, until the condition stabilizes, until the event is otherwise explained, or until the patient is lost to follow-up. For each patient, the duration of the study is approximately 96 weeks, from enrolment to last visit. Prior to enrolment there is a 60 day screening period. Addition of new cohorts and additional treatment regimens are anticipated for this study.

Conditions

Hepatitis B; Hepatitis D

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

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).

Group Type: EXPERIMENTAL

ARC-520

Intervention Type: 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.

antihistamine

Intervention Type: 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 2

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.

Group Type: EXPERIMENTAL

ARC-520

Intervention Type: 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.

entecavir

Intervention Type: DRUG

0.5 mg once daily; oral

pegylated interferon alpha 2a

Intervention Type: BIOLOGICAL

180 mcg; subcutaneous injection once weekly

tenofovir disoproxil

Intervention Type: DRUG

300 mg once daily; oral

antihistamine

Intervention Type: 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 3

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.

Group Type: EXPERIMENTAL

ARC-520

Intervention Type: 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.

entecavir

Intervention Type: DRUG

0.5 mg once daily; oral

pegylated interferon alpha 2a

Intervention Type: BIOLOGICAL

180 mcg; subcutaneous injection once weekly

tenofovir disoproxil

Intervention Type: DRUG

300 mg once daily; oral

antihistamine

Intervention Type: 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 4

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.

Group Type: EXPERIMENTAL

ARC-520

Intervention Type: 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.

entecavir

Intervention Type: DRUG

0.5 mg once daily; oral

pegylated interferon alpha 2a

Intervention Type: BIOLOGICAL

180 mcg; subcutaneous injection once weekly

tenofovir disoproxil

Intervention Type: DRUG

300 mg once daily; oral

antihistamine

Intervention Type: 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 5

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.

Group Type: EXPERIMENTAL

ARC-520

Intervention Type: 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.

entecavir

Intervention Type: DRUG

0.5 mg once daily; oral

pegylated interferon alpha 2a

Intervention Type: BIOLOGICAL

180 mcg; subcutaneous injection once weekly

tenofovir disoproxil

Intervention Type: DRUG

300 mg once daily; oral

antihistamine

Intervention Type: 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 6

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.

Group Type: EXPERIMENTAL

ARC-520

Intervention Type: 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.

entecavir

Intervention Type: DRUG

0.5 mg once daily; oral

pegylated interferon alpha 2a

Intervention Type: BIOLOGICAL

180 mcg; subcutaneous injection once weekly

tenofovir disoproxil

Intervention Type: DRUG

300 mg once daily; oral

antihistamine

Intervention Type: 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 7

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.

Group Type: EXPERIMENTAL

ARC-520

Intervention Type: 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.

pegylated interferon alpha 2a

Intervention Type: BIOLOGICAL

180 mcg; subcutaneous injection once weekly

antihistamine

Intervention Type: 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 8

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).

Group Type: EXPERIMENTAL

ARC-520

Intervention Type: 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.

antihistamine

Intervention Type: 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.

Interventions

ARC-520

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.

Intervention Type: DRUG

entecavir

0.5 mg once daily; oral

Intervention Type: DRUG

pegylated interferon alpha 2a

180 mcg; subcutaneous injection once weekly

Intervention Type: BIOLOGICAL

tenofovir disoproxil

300 mg once daily; oral

Intervention Type: DRUG

antihistamine

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.

Intervention Type: DRUG

Other Intervention Names

Baraclude; Peginterferon; Pegasys; Viread

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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)
• Use of recreational drugs such as cocaine, phencyclidine (PCP), and methamphetamines, within 1 year prior to the screening
• History of allergy to bee sting
• Clinically significant history of any alcoholic liver disease, cirrhosis, Wilson's disease, hemochromatosis, or alpha-1 antitrypsin deficiency
• Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction
• Clinically significant history or presence of poorly controlled/uncontrolled systemic disease
• Presence of any medical or psychiatric condition or social situation that impacts compliance or results in additional safety risk
• History of coagulopathy/stroke within past 6 months, and/or concurrent anticoagulant medication(s)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Arrowhead Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site 3

Camperdown, New South Wales, Australia

Research Site 8

Concord, New South Wales, Australia

Research Site 5

Darlinghurst, New South Wales, Australia

Research Site 1

Westmead, New South Wales, Australia

Research Site 9

Adelaide, South Australia, Australia

Research Site 6

Clayton, Victoria, Australia

Research Site 4

Fitzroy, Victoria, Australia

Research Site 2

Parkville, Victoria, Australia

Research Site 7

Nedlands, Washington, Australia

Research Site 13

Pleven, , Bulgaria

Research Site 10

Sofia, , Bulgaria

Research Site 11

Sofia, , Bulgaria

Research Site 12

Varna, , Bulgaria

Research Site 14

Hong Kong, , China

Research Site 25

Chisinau, , Moldova

Research Site 23

Papatoetoe, Aukland, New Zealand

Research Site 24

Dunedin, Otago-Southland, New Zealand

Research Site 21

Auckland, , New Zealand

Research Site 17

Busan, , South Korea

Research Site 19

Busan, , South Korea

Research Site 16

Daegu, , South Korea

Research Site 18

Seoul, , South Korea

Research Site 15

Seoul, , South Korea

Research Site 20

Seoul, , South Korea

Research Site 27

Douliu, Yunlin County, Taiwan

Research Site 26

Changhua, , Taiwan

Research Site 28

Kaohsiung City, , Taiwan

Research Site 29

Bangkok, , Thailand

Research Site 30

Bangkok, , Thailand

Research Site 32

Bangkok, , Thailand

Research Site 33

Chiang Mai, , Thailand

Research Site 31

Khon Kaen, , Thailand

Research Site 34

Pathum Thani, , Thailand

Countries

Australia; Bulgaria; China; Moldova; New Zealand; South Korea; Taiwan; Thailand

Other Identifiers

2015-005499-46

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Heparc-2008

Identifier Type: -

Identifier Source: org_study_id