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Company decision to discontinue trial
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| Name | Class |
|---|---|
| ICON Clinical Research | INDUSTRY |
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The purpose of this study is to determine whether ARC-520 in combination with entecavir is effective in the treatment of patients with chronic HBV Infection.
Treatment with ARC-520 for injection is expected to reduce all HBV proteins and replicative intermediates via ribonucleic acid (RNA) interference. The magnitude of the reduction and duration of effect will depend on the dose. Since to date ARC-520 has not been administered to patients with chronic HBV infection, the effective therapeutic dose in patients with chronic HBV infection is unknown. This study is designed to assess the antiviral activity of ARC-520, especially its effect on HBsAg, in patients with chronic HBV infection at different dose levels.
This is a multicenter, randomized, double-blind, placebo-controlled, single-dose escalation study of ARC 520 in combination with entecavir administered to participants with hepatitis B virus e antigen (HBeAg)-negative (Cohorts 1 through 4) or HBeAg-positive (Cohort 5) immune active, chronic HBV infection, followed by a two-dose open-label cohort (Cohort 6), three open-label single-dose cohorts in treatment-naïve participants (Cohorts 7, 11 and 12) and an open-label multi-dose extension study (Cohorts 8, 9, 10). Cohort 6 will investigate ARC-520 in combination with entecavir administered in two doses to participants with HBeAg-positive immune-active chronic HBV infection. Cohorts 7, 11 and 12 will enroll treatment-naïve participants. Cohort 8 will only enroll participants previously completing Cohorts 1-4. Cohort 9 will only enroll participants previously completing Cohort 5 or 6. Cohort 10 will only enroll participants previously completing Cohort 7.
Participants 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 (AEs), 12-lead electrocardiograms (ECGs), concomitant medication, blood sample collection for hematology, coagulation, chemistry, pharmacokinetic (PK) and exploratory pharmacodynamic (PD) measures, urinalysis, HBV serology, HBV genotyping and sequencing, follicle stimulating hormone (FSH) testing 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 participant is lost to follow-up.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ARC-520 Cohort 1 | Experimental | 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 | Placebo Comparator | 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 | Experimental | 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 | Experimental | 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 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ARC-520 | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Baseline, through Day 85 (Cohorts 1-7) and through 24 weeks post-last dose (last dose: Day 85 Cohort 9; Day 253 Cohort 10) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | 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. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bruce Given, MD | Arrowhead Pharmaceuticals, Inc. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site 1 | Pokfulam | Hong Kong | ||||
| Research Site 2 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33712437 | Derived | Yuen MF, Wong DK, Schluep T, Lai CL, Ferrari C, Locarnini S, Lo RC, Gish RG, Hamilton J, Wooddell CI, Mak LY, Given BD. Long-term serological, virological and histological responses to RNA inhibition by ARC-520 in Chinese chronic hepatitis B patients on entecavir treatment. Gut. 2022 Apr;71(4):789-797. doi: 10.1136/gutjnl-2020-323445. Epub 2021 Mar 12. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | ARC-520 Cohort 2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Main Study |
|
Not provided
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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 |
|
| Placebo Normal Saline Cohorts 1-5 | Experimental | 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 6 | Experimental | 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 | Experimental | 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) |
|
| ARC-520 Cohort 8 | Experimental | open-label multi-dose extension cohort: multiple IV doses of open-label ARC-520 (4.0 mg/kg every [Q]4 weeks) administered to HBeAg-negative participants with CHB receiving chronic entecavir therapy who completed Cohorts 1 through 4 |
|
| ARC-520 Cohort 9 | Experimental | 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 | Experimental | 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 |
|
| ARC-520 Cohort 11 | Experimental | a single IV dose of open-label ARC-520 5.0 mg/kg administered to treatment-naïve, HBeAg-positive participants with CHB |
|
| ARC-520 Cohort 12 | Experimental | a single IV dose of open-label ARC-520 6.0 mg/kg administered to treatment-naïve, HBeAg-positive participants with CHB |
|
| Placebo | Drug |
|
| entecavir | Drug |
|
|
| chlorpheniramine | Drug | In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection. |
|
| through Day 85 (Cohorts 1-7) and through 24 weeks post-last dose (last dose: Day 85 Cohort 9; Day 225 Cohort 10) |
| Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | 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. | Baseline, Day 29, Day 85 |
| Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Baseline, Days 1, 2, 3, 8, 15, 22, 29 |
| Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24), Cohorts 1-5 | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| Pharmacokinetics of ARC-520 of ARC-520 Product Constituents AD0009 and AD0010: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast), Cohorts 1-5 | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf), Cohorts 1-5 Only | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Maximum Observed Plasma Concentration (Cmax), Cohorts 1-5 | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Clearance (CL), Cohorts 1-5 | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Apparent Volume of Distribution During the Terminal Phase (Vz), Cohorts 1-5 | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Volume in Steady State (Vss), Cohorts 1-5 | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Rate Constant (Kel), Cohorts 1-5 | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Half-Life (t1/2), Cohorts 1-5 | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| Shatin |
| Hong Kong |
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
| FG002 | 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 |
| FG003 | 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 |
| FG004 | 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 |
| FG005 | 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 |
| FG006 | 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) |
| FG007 | 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 |
| FG008 | 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 |
| FG009 | 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 |
| COMPLETED |
|
| NOT COMPLETED |
|
| Extension Phase |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | ARC-520 Cohort 1 | 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 |
| BG001 | 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 |
| BG002 | 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 |
| BG003 | 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 |
| BG004 | 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 |
| BG005 | 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 |
| BG006 | 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) |
| BG007 | 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 |
| BG008 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| 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 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | 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. | Posted | Mean | Standard Deviation | IU/mL | Baseline, through Day 85 (Cohorts 1-7) and through 24 weeks post-last dose (last dose: Day 85 Cohort 9; Day 253 Cohort 10) |
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | 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. | 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. | Posted | Count of Participants | Participants | through Day 85 (Cohorts 1-7) and through 24 weeks post-last dose (last dose: Day 85 Cohort 9; Day 225 Cohort 10) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | 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. | Safety Population: all participants who received any amount of study drug or placebo, and had at least 1 postdose safety assessment. | Posted | Count of Participants | Participants | Baseline, Day 29, Day 85 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Pharmacokinetic (PK) Population: all participants who received at least 1 dose of study drug and had evaluable PK data. | Posted | Mean | Standard Deviation | ng/mL | Baseline, Days 1, 2, 3, 8, 15, 22, 29 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24), Cohorts 1-5 | PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data. | Posted | Mean | Standard Deviation | µg*hr/mL | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| ||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Pharmacokinetics of ARC-520 of ARC-520 Product Constituents AD0009 and AD0010: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast), Cohorts 1-5 | PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data. | Posted | Mean | Standard Deviation | µg*hr/mL | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| ||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf), Cohorts 1-5 Only | PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data. | Posted | Mean | Standard Deviation | µg*hr/mL | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| ||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Maximum Observed Plasma Concentration (Cmax), Cohorts 1-5 | PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data. | Posted | Mean | Standard Deviation | µg/mL | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| ||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Clearance (CL), Cohorts 1-5 | PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data. | Posted | Mean | Standard Deviation | mL/hr/kg | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| ||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Apparent Volume of Distribution During the Terminal Phase (Vz), Cohorts 1-5 | PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data. | Posted | Mean | Standard Deviation | mL/kg | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| ||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Volume in Steady State (Vss), Cohorts 1-5 | PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data. | Posted | Mean | Standard Deviation | mL/kg | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| ||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Rate Constant (Kel), Cohorts 1-5 | PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data. | Posted | Mean | Standard Deviation | 1/hr | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
| ||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Half-Life (t1/2), Cohorts 1-5 | PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data. | Posted | Median | Full Range | hours | Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose |
|
From first dose of study drug through Day 85 (Cohorts 1-7) and through 24 weeks post-last dose (last dose: Day 85 Cohort 9; Day 225 Cohort 10)
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ARC-520 Cohort 1 | 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 | 0 | 6 | 1 | 6 | ||
| EG001 | 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 | 0 | 6 | 4 | 6 | ||
| EG002 | 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 | 0 | 6 | 1 | 6 | ||
| EG003 | 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 | 0 | 6 | 0 | 6 | ||
| EG004 | 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 | 0 | 6 | 1 | 6 | ||
| EG005 | 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 | 0 | 6 | 1 | 6 | ||
| EG006 | 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 CHB | 0 | 12 | 1 | 12 | ||
| EG007 | 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 | 0 | 2 | 1 | 2 | ||
| EG008 | 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 | 0 | 8 | 7 | 8 | ||
| EG009 | 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 | 0 | 10 | 0 | 10 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Infusion site extravasation | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Temporomandibular joint syndrome | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Epigastric discomfort | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
|
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.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Operating Officer | Arrowhead Pharmaceuticals, Inc. | 626-304-3400 |
| ID | Term |
|---|---|
| D019694 | Hepatitis B, Chronic |
| D006505 | Hepatitis |
| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D018347 | Hepadnaviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006521 | Hepatitis, Chronic |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C000717093 | ARC-520 |
| C413685 | entecavir |
| D002744 | Chlorpheniramine |
| ID | Term |
|---|---|
| D010632 | Pheniramine |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Male |
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| Day 3 |
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| Day 8 |
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| Day 15 |
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| Day 22 |
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| Day 29 |
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| Day 43 |
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| Day 57 |
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| Day 85 |
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| Day 113 |
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| Day 141 |
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| Day 169 |
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| Day 197 |
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| Day 225 |
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| Day 253 |
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| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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 |
| OG005 | 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 |
| OG006 | 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 CHB |
| OG007 | 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 |
| OG008 | 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 |
| OG009 | 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 |
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| 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 |
| OG004 | 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 |
| OG005 | 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 |
| OG006 | 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 CHB |
| OG007 | 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 |
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| OG004 | 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 |
| OG005 | 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 CHB |
| OG006 | 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 |
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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
| OG004 | 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 |
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|
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 |
| OG004 | 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 |
|
|
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 |
| OG004 | 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 |
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|
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
| OG004 | 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 |
|
|
| OG004 | 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 |
|
|
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
| OG004 | 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 |
|
|
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
| OG004 | 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 |
|
|
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
| OG004 | 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 |
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|
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
| OG004 | 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 |
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