Hepatitis B, Chronic
Conditions
Keywords
HBV, Hepatitis
Brief summary
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.
Detailed description
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.
Interventions
DRUGARC-520
DRUGPlacebo
DRUGentecavir
DRUGchlorpheniramine
In all cohorts, each participant received an 8 mg dose of oral chlorpheniramine 2 hours prior to each administration of ARC-520 Injection.
Sponsors
ICON Clinical Research
Arrowhead Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of HBeAg negative and immune active chronic HBV infection (Cohorts 1-4, 8) * Diagnosis of HBeAg positive and immune active chronic HBV infection (Cohorts 5-6, 9) * Diagnosis of HBeAg negative or HBeAg positive and immune active or tolerant chronic HBV infection (Cohorts 7, 10, 11 & 12) * Patients with \> 6 months of continuous, 0.5 mg/day oral entecavir, and a willingness to continue taking entecavir throughout the study (Cohorts 1-6, 8-9). * Patients naive to entecavir (never on entecavir or on entecavir \<30 days prior to screening) and a willingness to take entecavir and willingness to continue taking entecavir throughout the study (Cohorts 7, 11 & 12). Key
Exclusion criteria
* Female patients that have a positive pregnancy test or are lactating. * Acute signs of hepatitis/other infection (eg, moderate fever, jaundice, nausea, vomiting, and abdominal pain) evident within 4 weeks of screening and/or at the screening examination. * Patients with antiviral therapy other than entecavir within 3 months of screening or prior treatment with interferon or a toll receptor agonist in the last 5 years. * Use within the last 6 months or an anticipated requirement for anticoagulants, corticosteroids, immunomodulators, or immunosuppressants. * Has any history of autoimmune disease especially autoimmune hepatitis. * Has human immunodeficiency virus (HIV) infection, as shown by the presence of anti-HIV antibody (sero-positive). * Is sero-positive for hepatitis C virus (HCV), and/or a history of delta virus hepatitis. * Has a history of allergy to bee venom or history of hypersensitivity reaction requiring an emergency visit to a physician or hospital and/or requirement for treatment with steroids and/or epinephrine.
Design outcomes
Primary
| Measure | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Baseline, Day 29, 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. |
| 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 | — |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | through Day 85 (Cohorts 1-7) and through 24 weeks post-last dose (last dose: Day 85 Cohort 9; Day 225 Cohort 10) | 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. |
| 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 | — |
| 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 | — |
Countries
Hong Kong
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 6 |
| 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 | 6 |
| 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 | 6 |
| 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 | 6 |
| 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 | 6 |
| 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 | 6 |
| 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) | 12 |
| 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 | 10 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Extension Phase | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 8 |
Baseline characteristics
| Characteristic | ARC-520 Cohort 1 | ARC-520 Cohort 2 | ARC-520 Cohort 3 | ARC-520 Cohort 4 | ARC-520 Cohort 5 | ARC-520 Cohort 6 | ARC-520 Cohort 7 | Placebo Normal Saline Cohorts 1-5 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 49.0 years STANDARD_DEVIATION 8.22 | 43.0 years STANDARD_DEVIATION 4.15 | 42.0 years STANDARD_DEVIATION 1.79 | 39.8 years STANDARD_DEVIATION 2.04 | 39.5 years STANDARD_DEVIATION 7.23 | 33.3 years STANDARD_DEVIATION 4.23 | 39.8 years STANDARD_DEVIATION 10.12 | 44.4 years STANDARD_DEVIATION 9.09 | 41.4 years STANDARD_DEVIATION 7.94 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 3 Participants | 5 Participants | 2 Participants | 20 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 3 Participants | 5 Participants | 4 Participants | 3 Participants | 7 Participants | 8 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 4 / 6 | 1 / 6 | 0 / 6 | 1 / 6 | 1 / 6 | 1 / 12 | 1 / 2 | 7 / 8 | 0 / 10 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 2 | 0 / 8 | 0 / 10 |
Outcome results
Primary
Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG)
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARC-520 Cohort 1 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 43 | -1020.1 IU/mL | Standard Deviation 1252.98 |
| ARC-520 Cohort 1 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 15 | -1055.1 IU/mL | Standard Deviation 1900.89 |
| ARC-520 Cohort 1 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 85 | -670.1 IU/mL | Standard Deviation 1825.99 |
| ARC-520 Cohort 1 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 22 | -1225.4 IU/mL | Standard Deviation 1967.15 |
| ARC-520 Cohort 1 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 29 | -579.1 IU/mL | Standard Deviation 352.71 |
| ARC-520 Cohort 1 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 8 | -928.1 IU/mL | Standard Deviation 1285.26 |
| ARC-520 Cohort 1 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 3 | -554.8 IU/mL | Standard Deviation 861.86 |
| ARC-520 Cohort 2 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 15 | -2260.8 IU/mL | Standard Deviation 4022.82 |
| ARC-520 Cohort 2 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 3 | -1194.0 IU/mL | Standard Deviation 2083.72 |
| ARC-520 Cohort 2 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 29 | -1826.3 IU/mL | Standard Deviation 2618.78 |
| ARC-520 Cohort 2 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 43 | -1288.8 IU/mL | Standard Deviation 1498.6 |
| ARC-520 Cohort 2 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 8 | -2179.2 IU/mL | Standard Deviation 3170.68 |
| ARC-520 Cohort 2 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 85 | -542.8 IU/mL | Standard Deviation 1815.34 |
| ARC-520 Cohort 2 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 57 | -1056.7 IU/mL | Standard Deviation 773.69 |
| ARC-520 Cohort 2 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 22 | -2266.2 IU/mL | Standard Deviation 3868.9 |
| ARC-520 Cohort 3 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 85 | -2119.3 IU/mL | Standard Deviation 1717.17 |
| ARC-520 Cohort 3 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 29 | 93.3 IU/mL | Standard Deviation 2425.68 |
| ARC-520 Cohort 3 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 57 | -2330.1 IU/mL | Standard Deviation 1676.5 |
| ARC-520 Cohort 3 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 3 | -1003.6 IU/mL | Standard Deviation 949.36 |
| ARC-520 Cohort 3 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 8 | -884.3 IU/mL | Standard Deviation 1296.49 |
| ARC-520 Cohort 3 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 43 | -1471.8 IU/mL | Standard Deviation 1625.3 |
| ARC-520 Cohort 3 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 15 | -470.8 IU/mL | Standard Deviation 2025.31 |
| ARC-520 Cohort 3 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 22 | -204.3 IU/mL | Standard Deviation 2077.12 |
| ARC-520 Cohort 4 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 85 | -926.3 IU/mL | Standard Deviation 1406.29 |
| ARC-520 Cohort 4 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 22 | -2978.8 IU/mL | Standard Deviation 3536.73 |
| ARC-520 Cohort 4 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 15 | -3069.0 IU/mL | Standard Deviation 3923.45 |
| ARC-520 Cohort 4 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 3 | -1501.0 IU/mL | Standard Deviation 1930.12 |
| ARC-520 Cohort 4 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 57 | -2813.0 IU/mL | Standard Deviation 2665.97 |
| ARC-520 Cohort 4 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 43 | -3219.8 IU/mL | Standard Deviation 3601.7 |
| ARC-520 Cohort 4 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 29 | -2972.8 IU/mL | Standard Deviation 3506.01 |
| ARC-520 Cohort 4 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 8 | -2591.2 IU/mL | Standard Deviation 3304.72 |
| ARC-520 Cohort 5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 57 | -1536.0 IU/mL | Standard Deviation 1373.46 |
| ARC-520 Cohort 5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 29 | -1964.3 IU/mL | Standard Deviation 2501.62 |
| ARC-520 Cohort 5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 43 | -1939.7 IU/mL | Standard Deviation 2277.79 |
| ARC-520 Cohort 5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 85 | -537.5 IU/mL | Standard Deviation 1901.16 |
| ARC-520 Cohort 5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 3 | -1664.7 IU/mL | Standard Deviation 2375.62 |
| ARC-520 Cohort 5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 22 | -1951.7 IU/mL | Standard Deviation 2819.85 |
| ARC-520 Cohort 5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 8 | -1789.8 IU/mL | Standard Deviation 2101.23 |
| ARC-520 Cohort 5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 15 | -1672.8 IU/mL | Standard Deviation 1892.73 |
| ARC-520 Cohort 6 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 85 | -791.0 IU/mL | Standard Deviation 457.04 |
| ARC-520 Cohort 6 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 3 | -948.0 IU/mL | Standard Deviation 1016.31 |
| ARC-520 Cohort 6 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 8 | -1344.0 IU/mL | Standard Deviation 1319.66 |
| ARC-520 Cohort 6 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 22 | -1553.7 IU/mL | Standard Deviation 1596.05 |
| ARC-520 Cohort 6 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 29 | -1532.3 IU/mL | Standard Deviation 1500.4 |
| ARC-520 Cohort 6 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 43 | -1566.8 IU/mL | Standard Deviation 1290.46 |
| ARC-520 Cohort 6 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 57 | -1370.7 IU/mL | Standard Deviation 872.64 |
| ARC-520 Cohort 7 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 85 | -20827.2 IU/mL | Standard Deviation 31753.76 |
| ARC-520 Cohort 7 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 57 | -22658.4 IU/mL | Standard Deviation 34292.84 |
| ARC-520 Cohort 7 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 8 | -20123.8 IU/mL | Standard Deviation 29795.99 |
| ARC-520 Cohort 7 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 3 | -12401.1 IU/mL | Standard Deviation 17661.02 |
| ARC-520 Cohort 7 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 22 | -23872.7 IU/mL | Standard Deviation 35753.39 |
| ARC-520 Cohort 7 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 43 | -23932.0 IU/mL | Standard Deviation 35929.8 |
| ARC-520 Cohort 7 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 29 | -24148.3 IU/mL | Standard Deviation 36256.02 |
| ARC-520 Cohort 7 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 15 | -22915.6 IU/mL | Standard Deviation 34381.59 |
| Placebo Normal Saline Cohorts 1-5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 29 | 168.8 IU/mL | Standard Deviation 460.59 |
| Placebo Normal Saline Cohorts 1-5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 15 | 236.6 IU/mL | Standard Deviation 321.17 |
| Placebo Normal Saline Cohorts 1-5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 57 | 156.1 IU/mL | Standard Deviation 527.4 |
| Placebo Normal Saline Cohorts 1-5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 8 | 42.2 IU/mL | Standard Deviation 568.32 |
| Placebo Normal Saline Cohorts 1-5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 3 | 43.3 IU/mL | Standard Deviation 267.6 |
| Placebo Normal Saline Cohorts 1-5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 43 | 58.3 IU/mL | Standard Deviation 411.6 |
| Placebo Normal Saline Cohorts 1-5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 85 | 225.4 IU/mL | Standard Deviation 393.81 |
| Placebo Normal Saline Cohorts 1-5 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 22 | 115.1 IU/mL | Standard Deviation 594.38 |
| ARC-520 Cohort 10 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 253 | -643 IU/mL | Standard Deviation 905 |
| ARC-520 Cohort 10 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 29 | -22617 IU/mL | Standard Deviation 32653 |
| ARC-520 Cohort 10 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 1 | -19222 IU/mL | Standard Deviation 27217 |
| ARC-520 Cohort 10 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 85 | -23305 IU/mL | Standard Deviation 32455 |
| ARC-520 Cohort 10 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 225 | -1249 IU/mL | Standard Deviation 1273 |
| ARC-520 Cohort 10 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 197 | -30234 IU/mL | Standard Deviation 34097 |
| ARC-520 Cohort 10 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 57 | -22840 IU/mL | Standard Deviation 32239 |
| ARC-520 Cohort 10 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 169 | -26481 IU/mL | Standard Deviation 33649 |
| ARC-520 Cohort 10 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 141 | -23182 IU/mL | Standard Deviation 32379 |
| ARC-520 Cohort 10 | Change From Baseline Over Time in Quantitative Hepatitis B Surface Antigen (HBsAG) | Day 113 | -23205 IU/mL | Standard Deviation 32362 |
Secondary
Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARC-520 Cohort 1 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 22 | 0.04 ng/mL | Standard Deviation 0.06 |
| ARC-520 Cohort 1 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 15 | 0.01 ng/mL | Standard Deviation 0.05 |
| ARC-520 Cohort 1 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 2 | 0.06 ng/mL | Standard Deviation 0.05 |
| ARC-520 Cohort 1 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 1 | 0 ng/mL | Standard Deviation 0 |
| ARC-520 Cohort 1 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 29 | 0.00 ng/mL | Standard Deviation 0.06 |
| ARC-520 Cohort 1 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 3 | -0.02 ng/mL | Standard Deviation 0.02 |
| ARC-520 Cohort 1 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 8 | -0.01 ng/mL | Standard Deviation 0.07 |
| ARC-520 Cohort 2 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 15 | -0.03 ng/mL | Standard Deviation 0.12 |
| ARC-520 Cohort 2 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 1 | 0 ng/mL | Standard Deviation 0 |
| ARC-520 Cohort 2 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 3 | -0.06 ng/mL | Standard Deviation 0.09 |
| ARC-520 Cohort 2 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 2 | 0.06 ng/mL | Standard Deviation 0.08 |
| ARC-520 Cohort 2 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 29 | -0.01 ng/mL | Standard Deviation 0.11 |
| ARC-520 Cohort 2 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 22 | -0.02 ng/mL | Standard Deviation 0.14 |
| ARC-520 Cohort 2 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 8 | -0.09 ng/mL | Standard Deviation 0.08 |
| ARC-520 Cohort 3 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 29 | 0.01 ng/mL | Standard Deviation 0.07 |
| ARC-520 Cohort 3 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 2 | 0.13 ng/mL | Standard Deviation 0.08 |
| ARC-520 Cohort 3 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 8 | -0.09 ng/mL | Standard Deviation 0.13 |
| ARC-520 Cohort 3 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 3 | -0.06 ng/mL | Standard Deviation 0.06 |
| ARC-520 Cohort 3 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 22 | -0.03 ng/mL | Standard Deviation 0.09 |
| ARC-520 Cohort 3 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 15 | -0.03 ng/mL | Standard Deviation 0.06 |
| ARC-520 Cohort 3 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 1 | 0 ng/mL | Standard Deviation 0 |
| ARC-520 Cohort 4 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 29 | 0.00 ng/mL | Standard Deviation 0.15 |
| ARC-520 Cohort 4 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 1 | 0 ng/mL | Standard Deviation 0 |
| ARC-520 Cohort 4 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 2 | 0.12 ng/mL | Standard Deviation 0.1 |
| ARC-520 Cohort 4 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 8 | -0.03 ng/mL | Standard Deviation 0.18 |
| ARC-520 Cohort 4 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 15 | 0.00 ng/mL | Standard Deviation 0.18 |
| ARC-520 Cohort 4 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 3 | 0.12 ng/mL | Standard Deviation 0.63 |
| ARC-520 Cohort 4 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 22 | 0.00 ng/mL | Standard Deviation 0.13 |
| ARC-520 Cohort 5 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 1 | 0 ng/mL | Standard Deviation 0 |
| ARC-520 Cohort 5 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 2 | -0.91 ng/mL | Standard Deviation 1.59 |
| ARC-520 Cohort 5 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 3 | -1.04 ng/mL | Standard Deviation 1.58 |
| ARC-520 Cohort 5 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 8 | -1.01 ng/mL | Standard Deviation 1.6 |
| ARC-520 Cohort 5 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 15 | -1.01 ng/mL | Standard Deviation 1.63 |
| ARC-520 Cohort 5 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 22 | -1.00 ng/mL | Standard Deviation 1.58 |
| ARC-520 Cohort 5 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 29 | -1.00 ng/mL | Standard Deviation 1.61 |
| ARC-520 Cohort 6 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 3 | 0.15 ng/mL | Standard Deviation 0.03 |
| ARC-520 Cohort 6 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 2 | 0.16 ng/mL | Standard Deviation 0.04 |
| ARC-520 Cohort 6 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 8 | 0.45 ng/mL | Standard Deviation 0.76 |
| ARC-520 Cohort 6 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 1 | 0 ng/mL | Standard Deviation 0 |
| ARC-520 Cohort 6 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 29 | 0.36 ng/mL | Standard Deviation 0.11 |
| ARC-520 Cohort 6 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 22 | 0.33 ng/mL | Standard Deviation 0.11 |
| ARC-520 Cohort 6 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 15 | 0.32 ng/mL | Standard Deviation 0.11 |
| ARC-520 Cohort 7 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 22 | -0.30 ng/mL | Standard Deviation 0.89 |
| ARC-520 Cohort 7 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 3 | -0.29 ng/mL | Standard Deviation 0.88 |
| ARC-520 Cohort 7 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 2 | -0.31 ng/mL | Standard Deviation 0.89 |
| ARC-520 Cohort 7 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 15 | -0.10 ng/mL | Standard Deviation 1.14 |
| ARC-520 Cohort 7 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 1 | 0 ng/mL | Standard Deviation 0 |
| ARC-520 Cohort 7 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 8 | -0.30 ng/mL | Standard Deviation 0.9 |
| ARC-520 Cohort 7 | Change From Baseline in Entecavir Plasma Trough Concentration, Cohorts 1-7 | Day 29 | -0.30 ng/mL | Standard Deviation 0.89 |
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARC-520 Cohort 1 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Baseline | 6 Participants |
| ARC-520 Cohort 1 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 85 | 6 Participants |
| ARC-520 Cohort 1 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 29 | 6 Participants |
| ARC-520 Cohort 2 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 85 | 6 Participants |
| ARC-520 Cohort 2 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Baseline | 6 Participants |
| ARC-520 Cohort 2 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 29 | 6 Participants |
| ARC-520 Cohort 3 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 85 | 6 Participants |
| ARC-520 Cohort 3 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Baseline | 6 Participants |
| ARC-520 Cohort 3 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 29 | 6 Participants |
| ARC-520 Cohort 4 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Baseline | 6 Participants |
| ARC-520 Cohort 4 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 29 | 6 Participants |
| ARC-520 Cohort 4 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 85 | 6 Participants |
| ARC-520 Cohort 5 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Baseline | 6 Participants |
| ARC-520 Cohort 5 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 29 | 6 Participants |
| ARC-520 Cohort 5 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 85 | 6 Participants |
| ARC-520 Cohort 6 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 29 | 6 Participants |
| ARC-520 Cohort 6 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Baseline | 6 Participants |
| ARC-520 Cohort 6 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 85 | 6 Participants |
| ARC-520 Cohort 7 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 29 | 11 Participants |
| ARC-520 Cohort 7 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Baseline | 12 Participants |
| ARC-520 Cohort 7 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 85 | 11 Participants |
| Placebo Normal Saline Cohorts 1-5 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Baseline | 10 Participants |
| Placebo Normal Saline Cohorts 1-5 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 29 | 10 Participants |
| Placebo Normal Saline Cohorts 1-5 | Number of Participants With Negative Bee Venom Allergy Test Results at Baseline, Day 29, and Day 85 | Day 85 | 10 Participants |
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARC-520 Cohort 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE related to study drug | 0 Participants |
| ARC-520 Cohort 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any mild TEAE | 1 Participants |
| ARC-520 Cohort 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any severe TEAE | 0 Participants |
| ARC-520 Cohort 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE related to study drug | 0 Participants |
| ARC-520 Cohort 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| ARC-520 Cohort 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE leading to death | 0 Participants |
| ARC-520 Cohort 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of treatment | 0 Participants |
| ARC-520 Cohort 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any moderate TEAE | 0 Participants |
| ARC-520 Cohort 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any life-threatening SAE | 0 Participants |
| ARC-520 Cohort 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 1 Participants |
| ARC-520 Cohort 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE leading to death | 0 Participants |
| ARC-520 Cohort 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any severe TEAE | 0 Participants |
| ARC-520 Cohort 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any life-threatening SAE | 0 Participants |
| ARC-520 Cohort 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 4 Participants |
| ARC-520 Cohort 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE related to study drug | 0 Participants |
| ARC-520 Cohort 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| ARC-520 Cohort 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any mild TEAE | 3 Participants |
| ARC-520 Cohort 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of treatment | 0 Participants |
| ARC-520 Cohort 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE related to study drug | 0 Participants |
| ARC-520 Cohort 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any moderate TEAE | 1 Participants |
| ARC-520 Cohort 3 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE leading to death | 0 Participants |
| ARC-520 Cohort 3 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of treatment | 0 Participants |
| ARC-520 Cohort 3 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any severe TEAE | 0 Participants |
| ARC-520 Cohort 3 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any life-threatening SAE | 0 Participants |
| ARC-520 Cohort 3 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 1 Participants |
| ARC-520 Cohort 3 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE related to study drug | 0 Participants |
| ARC-520 Cohort 3 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| ARC-520 Cohort 3 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE related to study drug | 0 Participants |
| ARC-520 Cohort 3 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any moderate TEAE | 0 Participants |
| ARC-520 Cohort 3 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any mild TEAE | 1 Participants |
| ARC-520 Cohort 4 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE related to study drug | 0 Participants |
| ARC-520 Cohort 4 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 0 Participants |
| ARC-520 Cohort 4 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE leading to death | 0 Participants |
| ARC-520 Cohort 4 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any mild TEAE | 0 Participants |
| ARC-520 Cohort 4 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any moderate TEAE | 0 Participants |
| ARC-520 Cohort 4 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any severe TEAE | 0 Participants |
| ARC-520 Cohort 4 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of treatment | 0 Participants |
| ARC-520 Cohort 4 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| ARC-520 Cohort 4 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE related to study drug | 0 Participants |
| ARC-520 Cohort 4 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any life-threatening SAE | 0 Participants |
| ARC-520 Cohort 5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any mild TEAE | 1 Participants |
| ARC-520 Cohort 5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of treatment | 0 Participants |
| ARC-520 Cohort 5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| ARC-520 Cohort 5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any life-threatening SAE | 0 Participants |
| ARC-520 Cohort 5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any moderate TEAE | 0 Participants |
| ARC-520 Cohort 5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE leading to death | 0 Participants |
| ARC-520 Cohort 5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE related to study drug | 0 Participants |
| ARC-520 Cohort 5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE related to study drug | 0 Participants |
| ARC-520 Cohort 5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 1 Participants |
| ARC-520 Cohort 5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any severe TEAE | 0 Participants |
| ARC-520 Cohort 6 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 1 Participants |
| ARC-520 Cohort 6 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| ARC-520 Cohort 6 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of treatment | 0 Participants |
| ARC-520 Cohort 6 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any moderate TEAE | 0 Participants |
| ARC-520 Cohort 6 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE related to study drug | 0 Participants |
| ARC-520 Cohort 6 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any life-threatening SAE | 0 Participants |
| ARC-520 Cohort 6 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any severe TEAE | 0 Participants |
| ARC-520 Cohort 6 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE leading to death | 0 Participants |
| ARC-520 Cohort 6 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any mild TEAE | 1 Participants |
| ARC-520 Cohort 6 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE related to study drug | 0 Participants |
| ARC-520 Cohort 7 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 1 Participants |
| ARC-520 Cohort 7 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any severe TEAE | 0 Participants |
| ARC-520 Cohort 7 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE related to study drug | 0 Participants |
| ARC-520 Cohort 7 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any mild TEAE | 1 Participants |
| ARC-520 Cohort 7 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of treatment | 0 Participants |
| ARC-520 Cohort 7 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE leading to death | 0 Participants |
| ARC-520 Cohort 7 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| ARC-520 Cohort 7 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE related to study drug | 0 Participants |
| ARC-520 Cohort 7 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any life-threatening SAE | 0 Participants |
| ARC-520 Cohort 7 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any moderate TEAE | 0 Participants |
| Placebo Normal Saline Cohorts 1-5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE related to study drug | 0 Participants |
| Placebo Normal Saline Cohorts 1-5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any mild TEAE | 1 Participants |
| Placebo Normal Saline Cohorts 1-5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| Placebo Normal Saline Cohorts 1-5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any moderate TEAE | 0 Participants |
| Placebo Normal Saline Cohorts 1-5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE related to study drug | 0 Participants |
| Placebo Normal Saline Cohorts 1-5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of treatment | 0 Participants |
| Placebo Normal Saline Cohorts 1-5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any severe TEAE | 0 Participants |
| Placebo Normal Saline Cohorts 1-5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 1 Participants |
| Placebo Normal Saline Cohorts 1-5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE leading to death | 0 Participants |
| Placebo Normal Saline Cohorts 1-5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any life-threatening SAE | 0 Participants |
| ARC-520 Cohort 9 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE related to study drug | 0 Participants |
| ARC-520 Cohort 9 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| ARC-520 Cohort 9 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any life-threatening SAE | 0 Participants |
| ARC-520 Cohort 9 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE related to study drug | 4 Participants |
| ARC-520 Cohort 9 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any mild TEAE | 7 Participants |
| ARC-520 Cohort 9 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any moderate TEAE | 0 Participants |
| ARC-520 Cohort 9 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE leading to death | 0 Participants |
| ARC-520 Cohort 9 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any severe TEAE | 0 Participants |
| ARC-520 Cohort 9 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of treatment | 0 Participants |
| ARC-520 Cohort 9 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 7 Participants |
| ARC-520 Cohort 10 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any mild TEAE | 0 Participants |
| ARC-520 Cohort 10 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any severe TEAE | 0 Participants |
| ARC-520 Cohort 10 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 0 Participants |
| ARC-520 Cohort 10 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| ARC-520 Cohort 10 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any moderate TEAE | 0 Participants |
| ARC-520 Cohort 10 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any life-threatening SAE | 0 Participants |
| ARC-520 Cohort 10 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE related to study drug | 0 Participants |
| ARC-520 Cohort 10 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE leading to death | 0 Participants |
| ARC-520 Cohort 10 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of treatment | 0 Participants |
| ARC-520 Cohort 10 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE related to study drug | 0 Participants |
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
Time frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose
Population: PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARC-520 Cohort 1 | 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 | AD0009 | 81.4 µg*hr/mL | Standard Deviation 9.25 |
| ARC-520 Cohort 1 | 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 | AD0010 | 97.6 µg*hr/mL | Standard Deviation 9.77 |
| ARC-520 Cohort 2 | 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 | AD0009 | 196 µg*hr/mL | Standard Deviation 66.3 |
| ARC-520 Cohort 2 | 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 | AD0010 | 205 µg*hr/mL | Standard Deviation 50.2 |
| ARC-520 Cohort 3 | 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 | AD0009 | 218 µg*hr/mL | Standard Deviation 37.1 |
| ARC-520 Cohort 3 | 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 | AD0010 | 317 µg*hr/mL | Standard Deviation 50.7 |
| ARC-520 Cohort 4 | 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 | AD0010 | 385 µg*hr/mL | Standard Deviation 88 |
| ARC-520 Cohort 4 | 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 | AD0009 | 326 µg*hr/mL | Standard Deviation 87.3 |
| ARC-520 Cohort 5 | 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 | AD0009 | 356 µg*hr/mL | Standard Deviation 47.4 |
| ARC-520 Cohort 5 | 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 | AD0010 | 434 µg*hr/mL | Standard Deviation 53.3 |
Secondary
Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Apparent Volume of Distribution During the Terminal Phase (Vz), Cohorts 1-5
Time frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose
Population: PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARC-520 Cohort 1 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Apparent Volume of Distribution During the Terminal Phase (Vz), Cohorts 1-5 | AD0010 | 39.4 mL/kg | Standard Deviation 5.01 |
| ARC-520 Cohort 1 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Apparent Volume of Distribution During the Terminal Phase (Vz), Cohorts 1-5 | AD0009 | 39.5 mL/kg | Standard Deviation 4.13 |
| ARC-520 Cohort 2 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Apparent Volume of Distribution During the Terminal Phase (Vz), Cohorts 1-5 | AD0010 | 46.1 mL/kg | Standard Deviation 9.99 |
| ARC-520 Cohort 2 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Apparent Volume of Distribution During the Terminal Phase (Vz), Cohorts 1-5 | AD0009 | 43.2 mL/kg | Standard Deviation 15.8 |
| ARC-520 Cohort 3 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Apparent Volume of Distribution During the Terminal Phase (Vz), Cohorts 1-5 | AD0009 | 45.7 mL/kg | Standard Deviation 5.72 |
| ARC-520 Cohort 3 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Apparent Volume of Distribution During the Terminal Phase (Vz), Cohorts 1-5 | AD0010 | 37.1 mL/kg | Standard Deviation 2.52 |
| ARC-520 Cohort 4 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Apparent Volume of Distribution During the Terminal Phase (Vz), Cohorts 1-5 | AD0009 | 39.0 mL/kg | Standard Deviation 7.27 |
| ARC-520 Cohort 4 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Apparent Volume of Distribution During the Terminal Phase (Vz), Cohorts 1-5 | AD0010 | 37.9 mL/kg | Standard Deviation 5.83 |
| ARC-520 Cohort 5 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Apparent Volume of Distribution During the Terminal Phase (Vz), Cohorts 1-5 | AD0009 | 35.4 mL/kg | Standard Deviation 4.06 |
| ARC-520 Cohort 5 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Apparent Volume of Distribution During the Terminal Phase (Vz), Cohorts 1-5 | AD0010 | 36.9 mL/kg | Standard Deviation 3.18 |
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
Time frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose
Population: PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARC-520 Cohort 1 | 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 | AD0009 | 81.4 µg*hr/mL | Standard Deviation 9.26 |
| ARC-520 Cohort 1 | 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 | AD0010 | 97.8 µg*hr/mL | Standard Deviation 9.8 |
| ARC-520 Cohort 2 | 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 | AD0009 | 196 µg*hr/mL | Standard Deviation 66.3 |
| ARC-520 Cohort 2 | 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 | AD0010 | 207 µg*hr/mL | Standard Deviation 51.1 |
| ARC-520 Cohort 3 | 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 | AD0009 | 218 µg*hr/mL | Standard Deviation 37.2 |
| ARC-520 Cohort 3 | 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 | AD0010 | 318 µg*hr/mL | Standard Deviation 51.2 |
| ARC-520 Cohort 4 | 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 | AD0010 | 386 µg*hr/mL | Standard Deviation 88.6 |
| ARC-520 Cohort 4 | 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 | AD0009 | 326 µg*hr/mL | Standard Deviation 87.4 |
| ARC-520 Cohort 5 | 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 | AD0009 | 356 µg*hr/mL | Standard Deviation 47.4 |
| ARC-520 Cohort 5 | 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 | AD0010 | 435 µg*hr/mL | Standard Deviation 53.8 |
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
Time frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose
Population: PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARC-520 Cohort 1 | 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 | AD0009 | 79.1 µg*hr/mL | Standard Deviation 8.28 |
| ARC-520 Cohort 1 | 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 | AD0010 | 93.0 µg*hr/mL | Standard Deviation 9.11 |
| ARC-520 Cohort 2 | 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 | AD0009 | 185 µg*hr/mL | Standard Deviation 61.2 |
| ARC-520 Cohort 2 | 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 | AD0010 | 190 µg*hr/mL | Standard Deviation 43.2 |
| ARC-520 Cohort 3 | 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 | AD0009 | 212 µg*hr/mL | Standard Deviation 34.7 |
| ARC-520 Cohort 3 | 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 | AD0010 | 301 µg*hr/mL | Standard Deviation 43.9 |
| ARC-520 Cohort 4 | 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 | AD0010 | 370 µg*hr/mL | Standard Deviation 80.5 |
| ARC-520 Cohort 4 | 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 | AD0009 | 318 µg*hr/mL | Standard Deviation 82.3 |
| ARC-520 Cohort 5 | 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 | AD0009 | 349 µg*hr/mL | Standard Deviation 45.2 |
| ARC-520 Cohort 5 | 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 | AD0010 | 412 µg*hr/mL | Standard Deviation 47.5 |
Secondary
Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Clearance (CL), Cohorts 1-5
Time frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose
Population: PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARC-520 Cohort 1 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Clearance (CL), Cohorts 1-5 | AD0010 | 5.16 mL/hr/kg | Standard Deviation 0.522 |
| ARC-520 Cohort 1 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Clearance (CL), Cohorts 1-5 | AD0009 | 6.21 mL/hr/kg | Standard Deviation 0.724 |
| ARC-520 Cohort 2 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Clearance (CL), Cohorts 1-5 | AD0009 | 5.58 mL/hr/kg | Standard Deviation 1.84 |
| ARC-520 Cohort 2 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Clearance (CL), Cohorts 1-5 | AD0010 | 5.08 mL/hr/kg | Standard Deviation 1.19 |
| ARC-520 Cohort 3 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Clearance (CL), Cohorts 1-5 | AD0010 | 4.84 mL/hr/kg | Standard Deviation 0.952 |
| ARC-520 Cohort 3 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Clearance (CL), Cohorts 1-5 | AD0009 | 7.11 mL/hr/kg | Standard Deviation 1.56 |
| ARC-520 Cohort 4 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Clearance (CL), Cohorts 1-5 | AD0009 | 6.47 mL/hr/kg | Standard Deviation 1.51 |
| ARC-520 Cohort 4 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Clearance (CL), Cohorts 1-5 | AD0010 | 5.41 mL/hr/kg | Standard Deviation 1.19 |
| ARC-520 Cohort 5 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Clearance (CL), Cohorts 1-5 | AD0010 | 4.65 mL/hr/kg | Standard Deviation 0.586 |
| ARC-520 Cohort 5 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Clearance (CL), Cohorts 1-5 | AD0009 | 5.70 mL/hr/kg | Standard Deviation 0.781 |
Secondary
Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Maximum Observed Plasma Concentration (Cmax), Cohorts 1-5
Time frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose
Population: PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARC-520 Cohort 1 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Maximum Observed Plasma Concentration (Cmax), Cohorts 1-5 | AD0009 | 13.7 µg/mL | Standard Deviation 2.42 |
| ARC-520 Cohort 1 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Maximum Observed Plasma Concentration (Cmax), Cohorts 1-5 | AD0010 | 12.7 µg/mL | Standard Deviation 2.07 |
| ARC-520 Cohort 2 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Maximum Observed Plasma Concentration (Cmax), Cohorts 1-5 | AD0009 | 26.4 µg/mL | Standard Deviation 6.84 |
| ARC-520 Cohort 2 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Maximum Observed Plasma Concentration (Cmax), Cohorts 1-5 | AD0010 | 22.5 µg/mL | Standard Deviation 2.74 |
| ARC-520 Cohort 3 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Maximum Observed Plasma Concentration (Cmax), Cohorts 1-5 | AD0009 | 33.5 µg/mL | Standard Deviation 1.78 |
| ARC-520 Cohort 3 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Maximum Observed Plasma Concentration (Cmax), Cohorts 1-5 | AD0010 | 39.7 µg/mL | Standard Deviation 2.6 |
| ARC-520 Cohort 4 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Maximum Observed Plasma Concentration (Cmax), Cohorts 1-5 | AD0010 | 50.5 µg/mL | Standard Deviation 10.6 |
| ARC-520 Cohort 4 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Maximum Observed Plasma Concentration (Cmax), Cohorts 1-5 | AD0009 | 54.8 µg/mL | Standard Deviation 9.59 |
| ARC-520 Cohort 5 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Maximum Observed Plasma Concentration (Cmax), Cohorts 1-5 | AD0009 | 58.2 µg/mL | Standard Deviation 5.88 |
| ARC-520 Cohort 5 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Maximum Observed Plasma Concentration (Cmax), Cohorts 1-5 | AD0010 | 52.4 µg/mL | Standard Deviation 6.44 |
Secondary
Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Half-Life (t1/2), Cohorts 1-5
Time frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose
Population: PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ARC-520 Cohort 1 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Half-Life (t1/2), Cohorts 1-5 | AD0010 | 5.29 hours |
| ARC-520 Cohort 1 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Half-Life (t1/2), Cohorts 1-5 | AD0009 | 4.38 hours |
| ARC-520 Cohort 2 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Half-Life (t1/2), Cohorts 1-5 | AD0009 | 5.36 hours |
| ARC-520 Cohort 2 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Half-Life (t1/2), Cohorts 1-5 | AD0010 | 6.32 hours |
| ARC-520 Cohort 3 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Half-Life (t1/2), Cohorts 1-5 | AD0010 | 5.48 hours |
| ARC-520 Cohort 3 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Half-Life (t1/2), Cohorts 1-5 | AD0009 | 4.64 hours |
| ARC-520 Cohort 4 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Half-Life (t1/2), Cohorts 1-5 | AD0009 | 4.18 hours |
| ARC-520 Cohort 4 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Half-Life (t1/2), Cohorts 1-5 | AD0010 | 4.79 hours |
| ARC-520 Cohort 5 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Half-Life (t1/2), Cohorts 1-5 | AD0009 | 4.32 hours |
| ARC-520 Cohort 5 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Half-Life (t1/2), Cohorts 1-5 | AD0010 | 5.36 hours |
Secondary
Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Rate Constant (Kel), Cohorts 1-5
Time frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose
Population: PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARC-520 Cohort 1 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Rate Constant (Kel), Cohorts 1-5 | AD0009 | 0.157 1/hr | Standard Deviation 0.0115 |
| ARC-520 Cohort 1 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Rate Constant (Kel), Cohorts 1-5 | AD0010 | 0.132 1/hr | Standard Deviation 0.0131 |
| ARC-520 Cohort 2 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Rate Constant (Kel), Cohorts 1-5 | AD0009 | 0.132 1/hr | Standard Deviation 0.0242 |
| ARC-520 Cohort 2 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Rate Constant (Kel), Cohorts 1-5 | AD0010 | 0.111 1/hr | Standard Deviation 0.0188 |
| ARC-520 Cohort 3 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Rate Constant (Kel), Cohorts 1-5 | AD0009 | 0.154 1/hr | Standard Deviation 0.0135 |
| ARC-520 Cohort 3 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Rate Constant (Kel), Cohorts 1-5 | AD0010 | 0.130 1/hr | Standard Deviation 0.018 |
| ARC-520 Cohort 4 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Rate Constant (Kel), Cohorts 1-5 | AD0010 | 0.142 1/hr | Standard Deviation 0.0164 |
| ARC-520 Cohort 4 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Rate Constant (Kel), Cohorts 1-5 | AD0009 | 0.165 1/hr | Standard Deviation 0.012 |
| ARC-520 Cohort 5 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Rate Constant (Kel), Cohorts 1-5 | AD0009 | 0.161 1/hr | Standard Deviation 0.00614 |
| ARC-520 Cohort 5 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Terminal Elimination Rate Constant (Kel), Cohorts 1-5 | AD0010 | 0.126 1/hr | Standard Deviation 0.00793 |
Secondary
Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Volume in Steady State (Vss), Cohorts 1-5
Time frame: Day 1 predose, immediately prior to the end of infusion, 0.5, 1, 3, 6, 24, and 48 hours postdose
Population: PK Population: all participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ARC-520 Cohort 1 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Volume in Steady State (Vss), Cohorts 1-5 | AD0009 | 39.6 mL/kg | Standard Deviation 6.05 |
| ARC-520 Cohort 1 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Volume in Steady State (Vss), Cohorts 1-5 | AD0010 | 40.7 mL/kg | Standard Deviation 6.01 |
| ARC-520 Cohort 2 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Volume in Steady State (Vss), Cohorts 1-5 | AD0009 | 45.8 mL/kg | Standard Deviation 11.6 |
| ARC-520 Cohort 2 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Volume in Steady State (Vss), Cohorts 1-5 | AD0010 | 46.7 mL/kg | Standard Deviation 8.22 |
| ARC-520 Cohort 3 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Volume in Steady State (Vss), Cohorts 1-5 | AD0009 | 45.3 mL/kg | Standard Deviation 3.6 |
| ARC-520 Cohort 3 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Volume in Steady State (Vss), Cohorts 1-5 | AD0010 | 38.1 mL/kg | Standard Deviation 2.08 |
| ARC-520 Cohort 4 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Volume in Steady State (Vss), Cohorts 1-5 | AD0010 | 39.8 mL/kg | Standard Deviation 6.36 |
| ARC-520 Cohort 4 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Volume in Steady State (Vss), Cohorts 1-5 | AD0009 | 39.6 mL/kg | Standard Deviation 6.31 |
| ARC-520 Cohort 5 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Volume in Steady State (Vss), Cohorts 1-5 | AD0009 | 35.3 mL/kg | Standard Deviation 3.57 |
| ARC-520 Cohort 5 | Pharmacokinetics of ARC-520 Product Constituents AD0009 and AD0010: Volume in Steady State (Vss), Cohorts 1-5 | AD0010 | 38.5 mL/kg | Standard Deviation 4.21 |