Trial Outcomes & Findings for 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 (NCT NCT02065336)

NCT ID: NCT02065336

Last Updated: 2026-01-13

Results Overview

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

58 participants

Primary outcome timeframe

Baseline, through Day 85 (Cohorts 1-7) and through 24 weeks post-last dose (last dose: Day 85 Cohort 9; Day 253 Cohort 10)

Results posted on

2026-01-13

Participant Flow

No patients were enrolled in Cohorts 8, 11, or 12. Cohort 9 (n=2) and Cohort 10 (n=8) enrolled participants who previously completed treatment in other cohorts.

Participant milestones

Participant milestones
Measure	ARC-520 Cohort 1 a 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 a 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 a 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 a 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 a 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	ARC-520 Cohort 6 two 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 a 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)	Placebo Normal Saline Cohorts 1-5 a 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 9 open-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 open-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
Main Study COMPLETED	6	6	6	6	6	6	12	10	0	0
Main Study STARTED	6	6	6	6	6	6	12	10	0	0
Main Study NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Extension Phase STARTED	0	0	0	0	0	0	0	0	2	8
Extension Phase COMPLETED	0	0	0	0	0	0	0	0	0	0
Extension Phase NOT COMPLETED	0	0	0	0	0	0	0	0	2	8

Reasons for withdrawal

Reasons for withdrawal
Measure	ARC-520 Cohort 1 a 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 a 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 a 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 a 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 a 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	ARC-520 Cohort 6 two 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 a 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)	Placebo Normal Saline Cohorts 1-5 a 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 9 open-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 open-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
Extension Phase Study Terminated by Sponsor	0	0	0	0	0	0	0	0	2	8

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ARC-520 Cohort 1 n=6 Participants a single 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 n=6 Participants a 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 n=6 Participants a 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 n=6 Participants a 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 n=6 Participants a 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	ARC-520 Cohort 6 n=6 Participants two 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 n=12 Participants a 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)	Placebo Normal Saline Cohorts 1-5 n=10 Participants a 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	Total n=58 Participants Total of all reporting groups
Age, Continuous	49.0 years STANDARD_DEVIATION 8.22 • n=9 Participants	43.0 years STANDARD_DEVIATION 4.15 • n=6 Participants	42.0 years STANDARD_DEVIATION 1.79 • n=9 Participants	39.8 years STANDARD_DEVIATION 2.04 • n=205 Participants	39.5 years STANDARD_DEVIATION 7.23 • n=16 Participants	33.3 years STANDARD_DEVIATION 4.23 • n=82 Participants	39.8 years STANDARD_DEVIATION 10.12 • n=83 Participants	44.4 years STANDARD_DEVIATION 9.09 • n=576 Participants	41.4 years STANDARD_DEVIATION 7.94 • n=415 Participants
Sex: Female, Male Female	2 Participants n=9 Participants	2 Participants n=6 Participants	3 Participants n=9 Participants	1 Participants n=205 Participants	2 Participants n=16 Participants	3 Participants n=82 Participants	5 Participants n=83 Participants	2 Participants n=576 Participants	20 Participants n=415 Participants
Sex: Female, Male Male	4 Participants n=9 Participants	4 Participants n=6 Participants	3 Participants n=9 Participants	5 Participants n=205 Participants	4 Participants n=16 Participants	3 Participants n=82 Participants	7 Participants n=83 Participants	8 Participants n=576 Participants	38 Participants n=415 Participants

PRIMARY outcome

Timeframe: Baseline, through Day 85 (Cohorts 1-7) and through 24 weeks post-last dose (last dose: Day 85 Cohort 9; Day 253 Cohort 10)

Population: Pharmacodynamic (PD) Population: all participants who received at least 1 dose of study drug and had evaluable data from at least one postdose PD assessment according to the treatment the participants were assigned.

Outcome measures

Outcome measures
Measure	ARC-520 Cohort 9 open-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 1 n=6 Participants a single 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 n=6 Participants a 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 n=6 Participants a 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 n=6 Participants a 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 n=6 Participants a 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	ARC-520 Cohort 6 n=6 Participants two 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 n=12 Participants a 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)	Placebo Normal Saline Cohorts 1-5 n=10 Participants a 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 10 n=8 Participants open-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
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 22	—	-1225.4 IU/mL Standard Deviation 1967.15	-2266.2 IU/mL Standard Deviation 3868.90	-204.3 IU/mL Standard Deviation 2077.12	-2978.8 IU/mL Standard Deviation 3536.73	-1951.7 IU/mL Standard Deviation 2819.85	-1553.7 IU/mL Standard Deviation 1596.05	-23872.7 IU/mL Standard Deviation 35753.39	115.1 IU/mL Standard Deviation 594.38	—
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 29	—	-579.1 IU/mL Standard Deviation 352.71	-1826.3 IU/mL Standard Deviation 2618.78	93.3 IU/mL Standard Deviation 2425.68	-2972.8 IU/mL Standard Deviation 3506.01	-1964.3 IU/mL Standard Deviation 2501.62	-1532.3 IU/mL Standard Deviation 1500.40	-24148.3 IU/mL Standard Deviation 36256.02	168.8 IU/mL Standard Deviation 460.59	-22617 IU/mL Standard Deviation 32653
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 43	—	-1020.1 IU/mL Standard Deviation 1252.98	-1288.8 IU/mL Standard Deviation 1498.60	-1471.8 IU/mL Standard Deviation 1625.30	-3219.8 IU/mL Standard Deviation 3601.70	-1939.7 IU/mL Standard Deviation 2277.79	-1566.8 IU/mL Standard Deviation 1290.46	-23932.0 IU/mL Standard Deviation 35929.80	58.3 IU/mL Standard Deviation 411.60	—
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 57	—	—	-1056.7 IU/mL Standard Deviation 773.69	-2330.1 IU/mL Standard Deviation 1676.50	-2813.0 IU/mL Standard Deviation 2665.97	-1536.0 IU/mL Standard Deviation 1373.46	-1370.7 IU/mL Standard Deviation 872.64	-22658.4 IU/mL Standard Deviation 34292.84	156.1 IU/mL Standard Deviation 527.40	-22840 IU/mL Standard Deviation 32239
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 85	—	-670.1 IU/mL Standard Deviation 1825.99	-542.8 IU/mL Standard Deviation 1815.34	-2119.3 IU/mL Standard Deviation 1717.17	-926.3 IU/mL Standard Deviation 1406.29	-537.5 IU/mL Standard Deviation 1901.16	-791.0 IU/mL Standard Deviation 457.04	-20827.2 IU/mL Standard Deviation 31753.76	225.4 IU/mL Standard Deviation 393.81	-23305 IU/mL Standard Deviation 32455
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 113	—	—	—	—	—	—	—	—	—	-23205 IU/mL Standard Deviation 32362
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 141	—	—	—	—	—	—	—	—	—	-23182 IU/mL Standard Deviation 32379
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 169	—	—	—	—	—	—	—	—	—	-26481 IU/mL Standard Deviation 33649
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 197	—	—	—	—	—	—	—	—	—	-30234 IU/mL Standard Deviation 34097
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 225	—	—	—	—	—	—	—	—	—	-1249 IU/mL Standard Deviation 1273
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 253	—	—	—	—	—	—	—	—	—	-643 IU/mL Standard Deviation 905
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 1	—	—	—	—	—	—	—	—	—	-19222 IU/mL Standard Deviation 27217
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 3	—	-554.8 IU/mL Standard Deviation 861.86	-1194.0 IU/mL Standard Deviation 2083.72	-1003.6 IU/mL Standard Deviation 949.36	-1501.0 IU/mL Standard Deviation 1930.12	-1664.7 IU/mL Standard Deviation 2375.62	-948.0 IU/mL Standard Deviation 1016.31	-12401.1 IU/mL Standard Deviation 17661.02	43.3 IU/mL Standard Deviation 267.60	—
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 8	—	-928.1 IU/mL Standard Deviation 1285.26	-2179.2 IU/mL Standard Deviation 3170.68	-884.3 IU/mL Standard Deviation 1296.49	-2591.2 IU/mL Standard Deviation 3304.72	-1789.8 IU/mL Standard Deviation 2101.23	-1344.0 IU/mL Standard Deviation 1319.66	-20123.8 IU/mL Standard Deviation 29795.99	42.2 IU/mL Standard Deviation 568.32	—
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) Day 15	—	-1055.1 IU/mL Standard Deviation 1900.89	-2260.8 IU/mL Standard Deviation 4022.82	-470.8 IU/mL Standard Deviation 2025.31	-3069.0 IU/mL Standard Deviation 3923.45	-1672.8 IU/mL Standard Deviation 1892.73	—	-22915.6 IU/mL Standard Deviation 34381.59	236.6 IU/mL Standard Deviation 321.17	—

SECONDARY outcome

Timeframe: through Day 85 (Cohorts 1-7) and through 24 weeks post-last dose (last dose: Day 85 Cohort 9; Day 225 Cohort 10)

Population: Safety Population: all participants who received any amount of study drug or placebo, and had at least 1 postdose safety assessment. Data for Cohort 9 was not analyzed or summarized due to limited enrollment.

An adverse event (AE) is any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. An SAE is any AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is a medically important event or reaction.Events were categorized as mild, moderate or severe. TEAEs were defined as all AEs starting or worsening after commencement of treatment with investigational product. A treatment-related TEAE was one whose relationship to treatment was noted as unlikely, possibly, or probably related.

Outcome measures

Outcome measures
Measure	ARC-520 Cohort 9 n=8 Participants open-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 1 n=6 Participants a single 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 n=6 Participants a 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 n=6 Participants a 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 n=6 Participants a 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 n=6 Participants a 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	ARC-520 Cohort 6 n=6 Participants two 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 n=12 Participants a 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)	Placebo Normal Saline Cohorts 1-5 n=2 Participants a 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 10 n=10 Participants open-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
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any TEAE	7 Participants	1 Participants	4 Participants	1 Participants	0 Participants	1 Participants	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any mild TEAE	7 Participants	1 Participants	3 Participants	1 Participants	0 Participants	1 Participants	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any moderate TEAE	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any severe TEAE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any TEAE related to study drug	4 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any TEAE leading to discontinuation of treatment	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any SAE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any SAE related to study drug	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any life-threatening SAE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any SAE leading to death	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Day 29, Day 85

Population: Safety Population: all participants who received any amount of study drug or placebo, and had at least 1 postdose safety assessment.

Bee venom allergy tests were used to assess immunoglobulin E (IgE) in Cohorts 1-7. Analysis values less than 0.35 kU/L were taken as negative.

Outcome measures

Outcome measures
Measure	ARC-520 Cohort 9 open-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 1 n=6 Participants a single 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 n=6 Participants a 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 n=6 Participants a 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 n=6 Participants a 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 n=6 Participants a 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	ARC-520 Cohort 6 n=6 Participants two 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 n=12 Participants a 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)	Placebo Normal Saline Cohorts 1-5 n=10 Participants a 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 10 open-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
Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 Day 29	—	6 Participants	6 Participants	6 Participants	6 Participants	6 Participants	6 Participants	11 Participants	10 Participants	—
Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 Day 85	—	6 Participants	6 Participants	6 Participants	6 Participants	6 Participants	6 Participants	11 Participants	10 Participants	—
Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 Baseline	—	6 Participants	6 Participants	6 Participants	6 Participants	6 Participants	6 Participants	12 Participants	10 Participants	—

SECONDARY outcome

Timeframe: Baseline, Days 1, 2, 3, 8, 15, 22, 29

Population: Pharmacokinetic (PK) Population: all participants who received at least 1 dose of study drug and had evaluable PK data.

Outcome measures

Outcome measures
Measure	ARC-520 Cohort 9 open-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 1 n=6 Participants a single 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 n=6 Participants a 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 n=6 Participants a 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 n=12 Participants a 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 n=6 Participants a 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	ARC-520 Cohort 6 n=12 Participants two 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 n=10 Participants a 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)	Placebo Normal Saline Cohorts 1-5 a 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 10 open-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
Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 Day 1	—	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0	0 ng/mL Standard Deviation 0	—	—
Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 Day 2	—	0.06 ng/mL Standard Deviation 0.05	0.06 ng/mL Standard Deviation 0.08	0.13 ng/mL Standard Deviation 0.08	0.12 ng/mL Standard Deviation 0.10	-0.91 ng/mL Standard Deviation 1.59	0.16 ng/mL Standard Deviation 0.04	-0.31 ng/mL Standard Deviation 0.89	—	—
Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 Day 3	—	-0.02 ng/mL Standard Deviation 0.02	-0.06 ng/mL Standard Deviation 0.09	-0.06 ng/mL Standard Deviation 0.06	0.12 ng/mL Standard Deviation 0.63	-1.04 ng/mL Standard Deviation 1.58	0.15 ng/mL Standard Deviation 0.03	-0.29 ng/mL Standard Deviation 0.88	—	—
Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 Day 8	—	-0.01 ng/mL Standard Deviation 0.07	-0.09 ng/mL Standard Deviation 0.08	-0.09 ng/mL Standard Deviation 0.13	-0.03 ng/mL Standard Deviation 0.18	-1.01 ng/mL Standard Deviation 1.60	0.45 ng/mL Standard Deviation 0.76	-0.30 ng/mL Standard Deviation 0.90	—	—
Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 Day 15	—	0.01 ng/mL Standard Deviation 0.05	-0.03 ng/mL Standard Deviation 0.12	-0.03 ng/mL Standard Deviation 0.06	0.00 ng/mL Standard Deviation 0.18	-1.01 ng/mL Standard Deviation 1.63	0.32 ng/mL Standard Deviation 0.11	-0.10 ng/mL Standard Deviation 1.14	—	—
Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 Day 22	—	0.04 ng/mL Standard Deviation 0.06	-0.02 ng/mL Standard Deviation 0.14	-0.03 ng/mL Standard Deviation 0.09	0.00 ng/mL Standard Deviation 0.13	-1.00 ng/mL Standard Deviation 1.58	0.33 ng/mL Standard Deviation 0.11	-0.30 ng/mL Standard Deviation 0.89	—	—
Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 Day 29	—	0.00 ng/mL Standard Deviation 0.06	-0.01 ng/mL Standard Deviation 0.11	0.01 ng/mL Standard Deviation 0.07	0.00 ng/mL Standard Deviation 0.15	-1.00 ng/mL Standard Deviation 1.61	0.36 ng/mL Standard Deviation 0.11	-0.30 ng/mL Standard Deviation 0.89	—	—

SECONDARY outcome

Timeframe: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose