Study of ARC-520 With or Without Other Drugs Used in the... | NCT02577029

ID	Type	Description	Link
2015-005499-46	EudraCT Number

Label	Type	Description	Intervention Names
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.

Name	Type	Description	Arm Group Labels	Other Names
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.

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Considered Possibly or Probably Related to Treatment	The Principal Investigator (or medically qualified designee) will use clinical judgment to determine the relationship. An adverse event (AE) was considered "possibly related" when there is a reasonable possibility that the incident, experience, or outcome may have been caused by the product under investigation. An AE was considered "probably related" when there are facts, evidence, or arguments to suggest that the event is related to the product under investigation. Only AEs that occurred post-dose were considered treatment-emergent. Clinically significant abnormal laboratory findings or other abnormal assessments that are detected during the study or are present at baseline and significantly worsen following the start of the study will be reported as AEs.

Eligibility Module

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)

Facility	Status	City	State	ZIP	Country	Contacts
Research Site 3		Camperdown	New South Wales	2050	Australia
Research Site 8

ID	Title	Description
FG000	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).
FG001	Cohort 2

Arm/Group Information

ID	Title	Description
BG000	Cohort 1	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
BG001	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 PEG IFN alpha 2a for 48 weeks starting Day 87.
BG002	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.
BG003	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.
BG004	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.
BG005	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.
BG006	Cohort 7	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with 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.
BG007	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).
BG008	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

The study was terminated prior to any participant reaching Week 60 of treatment; therefore, this outcome measure could not be analyzed.

Posted

Baseline, Week 60

ID	Title	Description
OG000	Cohort 1	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
OG001	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 PEG IFN alpha 2a for 48 weeks starting Day 87.
OG002	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.
OG003	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.
OG004	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.
OG005	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.
OG006	Cohort 7	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with 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.
OG007	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).

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

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

The Principal Investigator (or medically qualified designee) will use clinical judgment to determine the relationship. An adverse event (AE) was considered "possibly related" when there is a reasonable possibility that the incident, experience, or outcome may have been caused by the product under investigation. An AE was considered "probably related" when there are facts, evidence, or arguments to suggest that the event is related to the product under investigation. Only AEs that occurred post-dose were considered treatment-emergent. Clinically significant abnormal laboratory findings or other abnormal assessments that are detected during the study or are present at baseline and significantly worsen following the start of the study will be reported as AEs.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Cohort 1	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
OG001	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 PEG IFN alpha 2a for 48 weeks starting Day 87.

Secondary

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

The qualitative HBsAg assay gives a binary result, positive or negative.

The study was terminated prior to any participant reaching Week 52 of treatment; therefore, this outcome measure could not be analyzed.

Posted

Weeks 52, 60, 72 and 96

ID	Title	Description
OG000	Cohort 1	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
OG001	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 PEG IFN alpha 2a for 48 weeks starting Day 87.
OG002	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.

Secondary

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

The study was terminated prior to any participant reaching Week 52 of treatment; therefore, this outcome measure could not be analyzed.

Posted

Weeks 52, 60, 72 and 96

ID	Title	Description
OG000	Cohort 1	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
OG001	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 PEG IFN alpha 2a for 48 weeks starting Day 87.
OG002	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.

Secondary

Time to HBsAg Loss

This analysis was not done since no events of HBsAg loss were observed to to Week 36. (No participant reached Week 96 of treatment due to study termination).

Posted

Baseline through Week 96

ID	Title	Description
OG000	Cohort 1	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
OG001	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 PEG IFN alpha 2a for 48 weeks starting Day 87.
OG002	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.
OG003

Secondary

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

This analysis was not done since no events of HBsAg loss were observed to to Week 36. (No participant reached Week 96 of treatment due to study termination).

Posted

Baseline through Week 96

ID	Title	Description
OG000	Cohort 1	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
OG001	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 PEG IFN alpha 2a for 48 weeks starting Day 87.
OG002	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.

Secondary

Percentage of Participants With Anti-HBs Seroconversion Over Time

The study was terminated prior to any participant reaching Week 52 of treatment; therefore, this outcome measure could not be analyzed.

Posted

Weeks 52, 60, 72 and 96

ID	Title	Description
OG000	Cohort 1	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
OG001	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 PEG IFN alpha 2a for 48 weeks starting Day 87.
OG002	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.
OG003

Secondary

Percentage of Participants With HBeAg Loss and Anti-Hepatitis B e Antigen (Anti-HBe) Seroconversion (if HBeAg-Positive at Study Entry) Over Time

The study was terminated prior to any participant reaching Week 52 of treatment; therefore, this outcome measure could not be analyzed.

Posted

Weeks 52, 60, 72 and 96

ID	Title	Description
OG000	Cohort 1	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
OG001	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 PEG IFN alpha 2a for 48 weeks starting Day 87.
OG002	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.

Secondary

Percentage of Participants With Resistance to ARC-520 Injection by Week 52

Resistance is defined as > 1.0 log IU/mL quantitative HBsAg (qHBsAg) increase from nadir, confirmed by repeat test.

The study was terminated prior to any participant reaching Week 52 of treatment; therefore, this outcome measure could not be analyzed.

Posted

Week 52

ID	Title	Description
OG000	Cohort 1	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
OG001	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 PEG IFN alpha 2a for 48 weeks starting Day 87.
OG002	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.

Secondary

Percentage of Participants With Resistance to the Combination Therapy From Baseline to Week 60

Resistance is defined as > 1.0 log IU/mL increase in HBV DNA from nadir, confirmed by repeat test.

The study was terminated prior to any participant reaching Week 60 of treatment; therefore, this outcome measure could not be analyzed.

Posted

Baseline, Week 60

ID	Title	Description
OG000	Cohort 1	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
OG001	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 PEG IFN alpha 2a for 48 weeks starting Day 87.
OG002	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.

Secondary

Percentage of Participants With HDV With Undetectable HDV Ribonucleic Acid (RNA) After 48 Weeks of Concomitant ARC-520 Injection and PEG IFN Alpha 2a Therapy Over Time (Cohort 7 Only)

The study was terminated prior to any participant reaching Week 52 of treatment; therefore, this outcome measure could not be analyzed.

Posted

Weeks 52, 60, 72 and 96

ID	Title	Description
OG000	Cohort 1	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
OG001	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 PEG IFN alpha 2a for 48 weeks starting Day 87.
OG002	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.

Secondary

Log Change From Baseline in Quantitative HBV Deoxyribonucleic Acid (DNA) Serum Levels Over Time

The study was terminated prior to any participant reaching Week 60 of treatment; therefore, this outcome measure could not be analyzed.

Posted

Baseline, Weeks 52, 60, 72 and 96

ID	Title	Description
OG000	Cohort 1	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
OG001	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 PEG IFN alpha 2a for 48 weeks starting Day 87.
OG002	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.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort 1	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	0	10	5	10
EG001	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 PEG IFN alpha 2a for 48 weeks starting Day 87.	0	2	0	2
EG002	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.	0	7	4	7
EG003	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.	0	12	5	12
EG004	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.	0	11	5	11
EG005	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.	1	13	8	13
EG006	Cohort 7	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with 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.	0	12	9	12
EG007	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).	0	12	6	12

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Leukopenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG0030 affected12 at risk EG0040 affected11 at risk EG0050 affected13 at risk EG0064 affected12 at risk EG0070 affected12 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0021 affected7 at risk EG003
Eye irritation	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0021 affected7 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0021 affected7 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected2 at risk EG0021 affected7 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0021 affected7 at risk EG003
Administration site bruise	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Asthenia	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Chest pain	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Chills	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Fatigue	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0022 affected7 at risk EG003
Feeling cold	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Feeling hot	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Hot flush	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Influenza like illness	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0021 affected7 at risk EG003
Injection site erythema	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0021 affected7 at risk EG003
Irritability	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Malaise	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0021 affected7 at risk EG003
Peripheral coldness	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Pyrexia	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Swelling	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Hepatitis	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Cytokine release syndrome	Immune system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0021 affected7 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Oral herpes	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Rhinitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Tonsillitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Viral infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0021 affected7 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0021 affected7 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
International normalised ratio increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Muscle tightness	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Dizziness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Head discomfort	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Headache	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Sedation	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Somnolence	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Syncope	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Tremor	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Euphoric mood	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Somnolence	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Renal colic	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Prostatitis	Reproductive system and breast disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0021 affected7 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0021 affected7 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Flushing	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0021 affected7 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Hernia repair	Surgical and medical procedures	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Skin neoplasm excision	Surgical and medical procedures	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Hypotension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Peripheral coldness	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003
Vasoconstriction	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected7 at risk EG003

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D018347	Hepadnaviridae Infections
D004266	DNA Virus Infections
D014777	Virus Diseases
D006525	Hepatitis, Viral, Human
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases
D012327	RNA Virus Infections

ID	Term
C000717093	ARC-520
C413685	entecavir
C100416	peginterferon alfa-2a
D000068698	Tenofovir
D006633	Histamine Antagonists

ID	Term
D063065	Organophosphonates
D009943	Organophosphorus Compounds
D009930	Organic Chemicals
D000225	Adenine
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D018494	Histamine Agents
D018377	Neurotransmitter Agents
D045504	Molecular Mechanisms of Pharmacological Action
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses
D045505	Physiological Effects of Drugs