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A Study of ARC-520 at Varying Infusion Rates in Healthy Adult Volunteers

A Phase 1, Open-Label Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ARC-520 at Varying Infusion Rates in Normal Adult Volunteers

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02535416
Enrollment
40
Registered
2015-08-28
Start date
2015-09-30
Completion date
2016-08-31
Last updated
2026-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Brief summary

Single doses of ARC-520 will be evaluated at varying infusion rates and by slow bolus push.

Detailed description

This is a single-center, open-label, sequential cohort, single-dose study of ARC-520 administered intravenously to healthy adult volunteers. Eligible subjects will receive a single intravenous injection of ARC-520. Up to 8 cohorts (a total of approximately 40 subjects) may be enrolled. ARC-520 (4.0 mg/kg) will be administered at increasing infusion rates up to a bolus push in cohort 5. In addition dose levels at 5.0 mg/kg and 6.0 mg/kg will be evaluated at an infusion rate of 0.9 mL/min. For each subject the duration of the study clinic visits is approximately 6 weeks; maximum study duration is approximately 17 weeks including follow-up telephone calls at Days 30, 60 and 90. Participants will undergo the following evaluations at regular intervals: medical history, physical examinations, bee venom allergy blood test, vital signs measurements, weight, adverse event monitoring, electrocardiograms (ECGs), telemetry, pregnancy test (females), concurrent medication, blood sample collection for hematology, coagulation, chemistry, pharmacokinetics, pharmacodynamics, and drug screens, and urinalysis.

Interventions

DRUGARC-520
DRUGcetirizine
DRUGdiphenhydramine

Sponsors

Arrowhead Pharmaceuticals
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes

Inclusion criteria

* Male or female, 18-55 years of age, inclusive * Able to provide written informed consent * BMI between 19.0 and 35.0 kg/m2, inclusive * 12-lead ECG at Screening and pre-dose with no clinically significant abnormalities * Highly effective, double barrier contraception (both male and female partners) during the study and for 3 months following the dose of ARC-520 * Willing and able to comply with all study assessments * Suitable venous access for blood sampling * Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and creatinine levels in the normal range * No abnormal finding of clinical relevance

Exclusion criteria

* Pregnant/lactating * Acute signs of hepatitis/other infection within 4 weeks of Screening * Concurrent use of anticoagulants, corticosteroids, immunomodulators, or immunosuppressants. * Use of prescription medication within 14 days prior to study treatment * Depot injection/implant other than birth control within 3 months of study treatment * Known diagnosis of diabetes mellitus * History of autoimmune disease especially autoimmune hepatitis. * Human immunodeficiency virus (HIV) infection * Sero-positive for hepatitis B virus (HBV) or hepatitis C virus (HCV) * Uncontrolled hypertension: blood pressure (BP) \> 150/100 mmHg * History of cardiac rhythm disturbances * Family history of congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death. * Currently uses medications known to prolong the corrected QT interval (QTc). * Symptomatic heart failure (per New York Heart Association guidelines) * Unstable angina, myocardial infarction, severe cardiovascular disease, transient ischemic attack (TIA) or cerebrovascular accident (CVA) within past 6 months * History of malignancy within last 5 years except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer * Major surgery within 3 months of Screening * History of alcohol and/or drug abuse \< 12 months from Screening * Regular use of alcohol within 6 months of Screening * Evidence of systemic acute inflammation, sepsis or hemolysis. * Clinically significant psychiatric disorder * Use of recreational drugs within 3 months of Screening or drugs, such as cocaine, phencyclidine (PCP), and methamphetamines, within 1 year of Screening * Positive urine drug screen * History of allergy or hypersensitivity reaction to bee venom * Positive reaction to the bee venom immunoglobulin E \[IgE\] test * Use of investigational agents or devices within 30 days of study dosing or current participation in an investigational study. * Clinically significant history/presence of any gastrointestinal pathology, unresolved gastrointestinal symptoms, liver or kidney disease * Cholangitis, cholecystitis, cholestasis, or duct obstruction * Clinically significant history/presence of neurological, endocrine, cardiovascular, pulmonary, hematological, immunologic, psychiatric, metabolic or other uncontrolled systemic disease * Blood donation or blood loss (500 mL) within 30 days prior to study treatment * History of fever within 2 weeks of Screening. * Excessive exercise/physical activity within 7 days of Screening or enrollment or planned during the study. * History of coagulopathy, stroke within six (6) months of baseline, and/or concurrent anticoagulant medication(s)

Design outcomes

Primary

MeasureTime frameDescription
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)post-dose through the end of study (Day 15 ± 1 day) plus 30 daysAn adverse event (AE) is defined as any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. TEAEs were defined as all AEs starting or worsening after commencement of treatment with investigational product.

Secondary

MeasureTime frameDescription
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) of the Analytes of ARC-520Day 1 pre-dose through 48 hours post-doseAnalytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting HBV) and MLP.
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero Extrapolated to Infinity (AUCinf) of the Analytes of ARC-520Day 1 pre-dose through 48 hours post-doseAnalytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting HBV) and MLP.
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of the Analytes of ARC-520Day 1 pre-dose through 48 hours post-doseAnalytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting HBV) and MLP.
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of the Analytes of ARC-520Day 1 pre-dose through 48 hours post-doseAnalytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting hepatitis B virus \[HBV\]) and melittin-like peptide (MLP).
Pharmacokinetics: Apparent Volume of Distribution (V) of the Analytes of ARC-520Day 1 pre-dose through 48 hours post-doseAnalytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting HBV) and MLP.
Pharmacokinetics: Terminal Elimination Rate Constant (Lambda z) of the Analytes of ARC-520Day 1 pre-dose through 48 hours post-doseAnalytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting HBV) and MLP.
Pharmacokinetics: Half-Life (t1/2) of the Analytes of ARC-520Day 1 pre-dose through 48 hours post-doseAnalytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting HBV) and MLP.
Pharmacokinetics: Clearance (CL) of the Analytes of ARC-520Day 1 pre-dose through 48 hours post-doseAnalytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting HBV) and MLP.

Countries

Australia

Participant flow

Participants by arm

ArmCount
ARC-520 Cohort 1
Single dose, intravenous administration of ARC-520 at 4.0 mg/kg 0.6 mL/min + cetirizine
4
ARC-520 Cohort 2A
Single dose, intravenous administration of ARC-520 at 4.0 mg/kg 0.9 mL/min + cetirizine
2
ARC-520 Cohort 2
Single dose, intravenous administration of ARC-520 at 4.0 mg/kg 0.75 mL/min + diphenhydramine
4
ARC-520 Cohort 3
Single dose, intravenous administration of ARC-520 at 4.0 mg/kg 0.9 mL/min + diphenhydramine
4
ARC-520 Cohort 4
Single dose, intravenous administration of ARC-520 at 4.0 mg/kg 1.2 mL/min + diphenhydramine
4
ARC-520 Cohort 5
Single dose, intravenous administration of ARC-520 at 4.0 mg/kg 1.5 mL/min + diphenhydramine
4
ARC-520 Cohort 6
Single dose, intravenous administration of ARC-520 at 4.0 mg/kg 5 minute slow bolus push + diphenhydramine
6
ARC-520 Cohort 7
Single dose, intravenous administration of ARC-520 at 5.0 mg/kg 0.9 mL/min + diphenhydramine
6
ARC-520 Cohort 8
Single dose, intravenous administration of ARC-520 at 6.0 mg/kg 0.9 mL/min + diphenhydramine
6
Total40

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005FG006FG007FG008
Overall StudyFamily bereavement overseas100000000

Baseline characteristics

CharacteristicARC-520 Cohort 1TotalARC-520 Cohort 8ARC-520 Cohort 7ARC-520 Cohort 6ARC-520 Cohort 5ARC-520 Cohort 4ARC-520 Cohort 3ARC-520 Cohort 2ARC-520 Cohort 2A
Age, Continuous23.10 Years
STANDARD_DEVIATION 1.49
28.75 Years
STANDARD_DEVIATION 8.74
31.87 Years
STANDARD_DEVIATION 8.86
31.19 Years
STANDARD_DEVIATION 11.06
28.03 Years
STANDARD_DEVIATION 7.79
28.73 Years
STANDARD_DEVIATION 11.15
30.05 Years
STANDARD_DEVIATION 9.78
27.36 Years
STANDARD_DEVIATION 4.91
29.02 Years
STANDARD_DEVIATION 13.89
25.96 Years
STANDARD_DEVIATION 7.83
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants4 Participants1 Participants1 Participants1 Participants1 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants2 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants3 Participants0 Participants0 Participants1 Participants0 Participants0 Participants1 Participants0 Participants0 Participants
Race (NIH/OMB)
White
3 Participants31 Participants4 Participants5 Participants4 Participants3 Participants4 Participants3 Participants4 Participants1 Participants
Sex: Female, Male
Female
2 Participants21 Participants1 Participants5 Participants2 Participants2 Participants3 Participants3 Participants1 Participants2 Participants
Sex: Female, Male
Male
2 Participants19 Participants5 Participants1 Participants4 Participants2 Participants1 Participants1 Participants3 Participants0 Participants

Adverse events

Event typeEG000
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
deaths
Total, all-cause mortality
0 / 40 / 20 / 40 / 40 / 40 / 40 / 60 / 60 / 6
other
Total, other adverse events
2 / 42 / 21 / 43 / 43 / 42 / 45 / 63 / 62 / 6
serious
Total, serious adverse events
0 / 40 / 20 / 40 / 40 / 40 / 40 / 60 / 60 / 6

Outcome results

Primary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) is defined as any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. TEAEs were defined as all AEs starting or worsening after commencement of treatment with investigational product.

Time frame: post-dose through the end of study (Day 15 ± 1 day) plus 30 days

Population: Safety Population: all enrolled participants

ArmMeasureValue (NUMBER)
ARC-520 Cohort 1Number of Participants With Treatment-Emergent Adverse Events (TEAEs)2 participants
ARC-520 Cohort 2ANumber of Participants With Treatment-Emergent Adverse Events (TEAEs)2 participants
ARC-520 Cohort 2Number of Participants With Treatment-Emergent Adverse Events (TEAEs)1 participants
ARC-520 Cohort 3Number of Participants With Treatment-Emergent Adverse Events (TEAEs)3 participants
ARC-520 Cohort 4Number of Participants With Treatment-Emergent Adverse Events (TEAEs)3 participants
ARC-520 Cohort 5Number of Participants With Treatment-Emergent Adverse Events (TEAEs)2 participants
ARC-520 Cohort 6Number of Participants With Treatment-Emergent Adverse Events (TEAEs)5 participants
ARC-520 Cohort 7Number of Participants With Treatment-Emergent Adverse Events (TEAEs)3 participants
ARC-520 Cohort 8Number of Participants With Treatment-Emergent Adverse Events (TEAEs)2 participants
Secondary

Pharmacokinetics: Apparent Volume of Distribution (V) of the Analytes of ARC-520

Analytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting HBV) and MLP.

Time frame: Day 1 pre-dose through 48 hours post-dose

Population: All participants with highest achievable infusion rate up to a slow bolus push (Cohort 6) and all participants receiving 4.0, 5.0 and 6.0 mg/kg using an infusion rate of 0.9 mL/min (Cohorts 3, 7 and 8) who had at least one PK sample collected

ArmMeasureGroupValue (MEAN)Dispersion
ARC-520 Cohort 1Pharmacokinetics: Apparent Volume of Distribution (V) of the Analytes of ARC-520Analyte AD000970.02 mL/kgStandard Deviation 19.42
ARC-520 Cohort 1Pharmacokinetics: Apparent Volume of Distribution (V) of the Analytes of ARC-520Analyte MLP58.03 mL/kgStandard Deviation 17.64
ARC-520 Cohort 1Pharmacokinetics: Apparent Volume of Distribution (V) of the Analytes of ARC-520Analyte AD001065.98 mL/kgStandard Deviation 18.44
ARC-520 Cohort 2APharmacokinetics: Apparent Volume of Distribution (V) of the Analytes of ARC-520Analyte AD000969.31 mL/kgStandard Deviation 8.53
ARC-520 Cohort 2APharmacokinetics: Apparent Volume of Distribution (V) of the Analytes of ARC-520Analyte MLP55.77 mL/kgStandard Deviation 7.25
ARC-520 Cohort 2APharmacokinetics: Apparent Volume of Distribution (V) of the Analytes of ARC-520Analyte AD001071.62 mL/kgStandard Deviation 4.74
ARC-520 Cohort 2Pharmacokinetics: Apparent Volume of Distribution (V) of the Analytes of ARC-520Analyte AD001079.68 mL/kgStandard Deviation 8.52
ARC-520 Cohort 2Pharmacokinetics: Apparent Volume of Distribution (V) of the Analytes of ARC-520Analyte AD000971.49 mL/kgStandard Deviation 9.4
ARC-520 Cohort 2Pharmacokinetics: Apparent Volume of Distribution (V) of the Analytes of ARC-520Analyte MLP63.92 mL/kgStandard Deviation 9.85
ARC-520 Cohort 3Pharmacokinetics: Apparent Volume of Distribution (V) of the Analytes of ARC-520Analyte AD000962.74 mL/kgStandard Deviation 9.28
ARC-520 Cohort 3Pharmacokinetics: Apparent Volume of Distribution (V) of the Analytes of ARC-520Analyte MLP56.49 mL/kgStandard Deviation 8.36
ARC-520 Cohort 3Pharmacokinetics: Apparent Volume of Distribution (V) of the Analytes of ARC-520Analyte AD001076.21 mL/kgStandard Deviation 12.89
Secondary

Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) of the Analytes of ARC-520

Analytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting HBV) and MLP.

Time frame: Day 1 pre-dose through 48 hours post-dose

Population: All participants with highest achievable infusion rate up to a slow bolus push (Cohort 6) and all participants receiving 4.0, 5.0 and 6.0 mg/kg using an infusion rate of 0.9 mL/min (Cohorts 3, 7 and 8) who had at least one PK sample collected

ArmMeasureGroupValue (MEAN)Dispersion
ARC-520 Cohort 1Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) of the Analytes of ARC-520Analyte AD0009361611 ng.hr/mLStandard Deviation 124315
ARC-520 Cohort 1Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) of the Analytes of ARC-520Analyte MLP1022752 ng.hr/mLStandard Deviation 178706
ARC-520 Cohort 1Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) of the Analytes of ARC-520Analyte AD0010433632 ng.hr/mLStandard Deviation 139292
ARC-520 Cohort 2APharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) of the Analytes of ARC-520Analyte AD0009340430 ng.hr/mLStandard Deviation 61108
ARC-520 Cohort 2APharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) of the Analytes of ARC-520Analyte MLP1021005 ng.hr/mLStandard Deviation 191504
ARC-520 Cohort 2APharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) of the Analytes of ARC-520Analyte AD0010422964 ng.hr/mLStandard Deviation 72513
ARC-520 Cohort 2Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) of the Analytes of ARC-520Analyte AD0010461601 ng.hr/mLStandard Deviation 84332
ARC-520 Cohort 2Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) of the Analytes of ARC-520Analyte AD0009416905 ng.hr/mLStandard Deviation 79670
ARC-520 Cohort 2Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) of the Analytes of ARC-520Analyte MLP1270330 ng.hr/mLStandard Deviation 195274
ARC-520 Cohort 3Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) of the Analytes of ARC-520Analyte AD0009638203 ng.hr/mLStandard Deviation 115032
ARC-520 Cohort 3Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) of the Analytes of ARC-520Analyte MLP1722485 ng.hr/mLStandard Deviation 212539
ARC-520 Cohort 3Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) of the Analytes of ARC-520Analyte AD0010698567 ng.hr/mLStandard Deviation 107649
Secondary

Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero Extrapolated to Infinity (AUCinf) of the Analytes of ARC-520

Analytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting HBV) and MLP.

Time frame: Day 1 pre-dose through 48 hours post-dose

Population: All participants with highest achievable infusion rate up to a slow bolus push (Cohort 6) and all participants receiving 4.0, 5.0 and 6.0 mg/kg using an infusion rate of 0.9 mL/min (Cohorts 3, 7 and 8) who had at least one PK sample collected

ArmMeasureGroupValue (MEAN)Dispersion
ARC-520 Cohort 1Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero Extrapolated to Infinity (AUCinf) of the Analytes of ARC-520Analyte AD0009361820 ng.hr/mLStandard Deviation 124381
ARC-520 Cohort 1Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero Extrapolated to Infinity (AUCinf) of the Analytes of ARC-520Analyte MLP1068557 ng.hr/mLStandard Deviation 160050
ARC-520 Cohort 1Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero Extrapolated to Infinity (AUCinf) of the Analytes of ARC-520Analyte AD0010434351 ng.hr/mLStandard Deviation 139573
ARC-520 Cohort 2APharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero Extrapolated to Infinity (AUCinf) of the Analytes of ARC-520Analyte AD0009340591 ng.hr/mLStandard Deviation 61237
ARC-520 Cohort 2APharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero Extrapolated to Infinity (AUCinf) of the Analytes of ARC-520Analyte MLP1080995 ng.hr/mLStandard Deviation 218046
ARC-520 Cohort 2APharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero Extrapolated to Infinity (AUCinf) of the Analytes of ARC-520Analyte AD0010425598 ng.hr/mLStandard Deviation 77283
ARC-520 Cohort 2Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero Extrapolated to Infinity (AUCinf) of the Analytes of ARC-520Analyte AD0010462837 ng.hr/mLStandard Deviation 85266
ARC-520 Cohort 2Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero Extrapolated to Infinity (AUCinf) of the Analytes of ARC-520Analyte AD0009417153 ng.hr/mLStandard Deviation 79832
ARC-520 Cohort 2Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero Extrapolated to Infinity (AUCinf) of the Analytes of ARC-520Analyte MLP1368448 ng.hr/mLStandard Deviation 207758
ARC-520 Cohort 3Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero Extrapolated to Infinity (AUCinf) of the Analytes of ARC-520Analyte AD0009638965 ng.hr/mLStandard Deviation 115557
ARC-520 Cohort 3Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero Extrapolated to Infinity (AUCinf) of the Analytes of ARC-520Analyte MLP1869597 ng.hr/mLStandard Deviation 282272
ARC-520 Cohort 3Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero Extrapolated to Infinity (AUCinf) of the Analytes of ARC-520Analyte AD0010703886 ng.hr/mLStandard Deviation 111074
Secondary

Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of the Analytes of ARC-520

Analytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting hepatitis B virus \[HBV\]) and melittin-like peptide (MLP).

Time frame: Day 1 pre-dose through 48 hours post-dose

Population: All participants with highest achievable infusion rate up to a slow bolus push (Cohort 6) and all participants receiving 4.0, 5.0 and 6.0 mg/kg using an infusion rate of 0.9 mL/min (Cohorts 3, 7 and 8) who had at least one pharmacokinetic (PK) sample collected

ArmMeasureGroupValue (MEAN)Dispersion
ARC-520 Cohort 1Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of the Analytes of ARC-520Analyte AD0009350027 ng.hr/mLStandard Deviation 120570
ARC-520 Cohort 1Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of the Analytes of ARC-520Analyte MLP839718 ng.hr/mLStandard Deviation 181756
ARC-520 Cohort 1Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of the Analytes of ARC-520Analyte AD0010411580 ng.hr/mLStandard Deviation 131789
ARC-520 Cohort 2APharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of the Analytes of ARC-520Analyte AD0009331953 ng.hr/mLStandard Deviation 58196
ARC-520 Cohort 2APharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of the Analytes of ARC-520Analyte MLP832929 ng.hr/mLStandard Deviation 132093
ARC-520 Cohort 2APharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of the Analytes of ARC-520Analyte AD0010393161 ng.hr/mLStandard Deviation 64540
ARC-520 Cohort 2Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of the Analytes of ARC-520Analyte AD0010431980 ng.hr/mLStandard Deviation 69927
ARC-520 Cohort 2Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of the Analytes of ARC-520Analyte AD0009403247 ng.hr/mLStandard Deviation 72519
ARC-520 Cohort 2Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of the Analytes of ARC-520Analyte MLP1015503 ng.hr/mLStandard Deviation 150276
ARC-520 Cohort 3Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of the Analytes of ARC-520Analyte AD0009605608 ng.hr/mLStandard Deviation 98952
ARC-520 Cohort 3Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of the Analytes of ARC-520Analyte MLP1364108 ng.hr/mLStandard Deviation 137352
ARC-520 Cohort 3Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of the Analytes of ARC-520Analyte AD0010630774 ng.hr/mLStandard Deviation 87136
Secondary

Pharmacokinetics: Clearance (CL) of the Analytes of ARC-520

Analytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting HBV) and MLP.

Time frame: Day 1 pre-dose through 48 hours post-dose

Population: All participants with highest achievable infusion rate up to a slow bolus push (Cohort 6) and all participants receiving 4.0, 5.0 and 6.0 mg/kg using an infusion rate of 0.9 mL/min (Cohorts 3, 7 and 8) who had at least one PK sample collected

ArmMeasureGroupValue (MEAN)Dispersion
ARC-520 Cohort 1Pharmacokinetics: Clearance (CL) of the Analytes of ARC-520Analyte AD000912.01 mL/hr/kgStandard Deviation 3.77
ARC-520 Cohort 1Pharmacokinetics: Clearance (CL) of the Analytes of ARC-520Analyte MLP3.80 mL/hr/kgStandard Deviation 0.51
ARC-520 Cohort 1Pharmacokinetics: Clearance (CL) of the Analytes of ARC-520Analyte AD00109.92 mL/hr/kgStandard Deviation 3
ARC-520 Cohort 2APharmacokinetics: Clearance (CL) of the Analytes of ARC-520Analyte AD000912.04 mL/hr/kgStandard Deviation 2.05
ARC-520 Cohort 2APharmacokinetics: Clearance (CL) of the Analytes of ARC-520Analyte MLP3.85 mL/hr/kgStandard Deviation 0.91
ARC-520 Cohort 2APharmacokinetics: Clearance (CL) of the Analytes of ARC-520Analyte AD00109.61 mL/hr/kgStandard Deviation 1.44
ARC-520 Cohort 2Pharmacokinetics: Clearance (CL) of the Analytes of ARC-520Analyte AD001011.13 mL/hr/kgStandard Deviation 2.17
ARC-520 Cohort 2Pharmacokinetics: Clearance (CL) of the Analytes of ARC-520Analyte AD000912.40 mL/hr/kgStandard Deviation 2.64
ARC-520 Cohort 2Pharmacokinetics: Clearance (CL) of the Analytes of ARC-520Analyte MLP3.73 mL/hr/kgStandard Deviation 0.58
ARC-520 Cohort 3Pharmacokinetics: Clearance (CL) of the Analytes of ARC-520Analyte AD00099.68 mL/hr/kgStandard Deviation 1.93
ARC-520 Cohort 3Pharmacokinetics: Clearance (CL) of the Analytes of ARC-520Analyte MLP3.27 mL/hr/kgStandard Deviation 0.47
ARC-520 Cohort 3Pharmacokinetics: Clearance (CL) of the Analytes of ARC-520Analyte AD00108.72 mL/hr/kgStandard Deviation 1.5
Secondary

Pharmacokinetics: Half-Life (t1/2) of the Analytes of ARC-520

Analytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting HBV) and MLP.

Time frame: Day 1 pre-dose through 48 hours post-dose

Population: All participants with highest achievable infusion rate up to a slow bolus push (Cohort 6) and all participants receiving 4.0, 5.0 and 6.0 mg/kg using an infusion rate of 0.9 mL/min (Cohorts 3, 7 and 8) who had at least one PK sample collected

ArmMeasureGroupValue (MEAN)Dispersion
ARC-520 Cohort 1Pharmacokinetics: Half-Life (t1/2) of the Analytes of ARC-520Analyte AD00094.10 hourStandard Deviation 0.73
ARC-520 Cohort 1Pharmacokinetics: Half-Life (t1/2) of the Analytes of ARC-520Analyte MLP10.41 hourStandard Deviation 2.01
ARC-520 Cohort 1Pharmacokinetics: Half-Life (t1/2) of the Analytes of ARC-520Analyte AD00104.68 hourStandard Deviation 1.03
ARC-520 Cohort 2APharmacokinetics: Half-Life (t1/2) of the Analytes of ARC-520Analyte AD00094.02 hourStandard Deviation 0.3
ARC-520 Cohort 2APharmacokinetics: Half-Life (t1/2) of the Analytes of ARC-520Analyte MLP10.44 hourStandard Deviation 2.29
ARC-520 Cohort 2APharmacokinetics: Half-Life (t1/2) of the Analytes of ARC-520Analyte AD00105.31 hourStandard Deviation 1.23
ARC-520 Cohort 2Pharmacokinetics: Half-Life (t1/2) of the Analytes of ARC-520Analyte AD00105.07 hourStandard Deviation 0.85
ARC-520 Cohort 2Pharmacokinetics: Half-Life (t1/2) of the Analytes of ARC-520Analyte AD00094.06 hourStandard Deviation 0.44
ARC-520 Cohort 2Pharmacokinetics: Half-Life (t1/2) of the Analytes of ARC-520Analyte MLP11.94 hourStandard Deviation 1.32
ARC-520 Cohort 3Pharmacokinetics: Half-Life (t1/2) of the Analytes of ARC-520Analyte AD00094.56 hourStandard Deviation 0.69
ARC-520 Cohort 3Pharmacokinetics: Half-Life (t1/2) of the Analytes of ARC-520Analyte MLP12.24 hourStandard Deviation 2.77
ARC-520 Cohort 3Pharmacokinetics: Half-Life (t1/2) of the Analytes of ARC-520Analyte AD00106.17 hourStandard Deviation 1.34
Secondary

Pharmacokinetics: Maximum Plasma Concentration (Cmax) of the Analytes of ARC-520

Analytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting HBV) and MLP.

Time frame: Day 1 pre-dose through 48 hours post-dose

Population: All participants with highest achievable infusion rate up to a slow bolus push (Cohort 6) and all participants receiving 4.0, 5.0 and 6.0 mg/kg using an infusion rate of 0.9 mL/min (Cohorts 3, 7 and 8) who had at least one PK sample collected

ArmMeasureGroupValue (MEAN)Dispersion
ARC-520 Cohort 1Pharmacokinetics: Maximum Plasma Concentration (Cmax) of the Analytes of ARC-520Analyte AD000954150 ng/mLStandard Deviation 15711
ARC-520 Cohort 1Pharmacokinetics: Maximum Plasma Concentration (Cmax) of the Analytes of ARC-520Analyte MLP76600 ng/mLStandard Deviation 19616
ARC-520 Cohort 1Pharmacokinetics: Maximum Plasma Concentration (Cmax) of the Analytes of ARC-520Analyte AD001049650 ng/mLStandard Deviation 14058
ARC-520 Cohort 2APharmacokinetics: Maximum Plasma Concentration (Cmax) of the Analytes of ARC-520Analyte AD000948880 ng/mLStandard Deviation 6155
ARC-520 Cohort 2APharmacokinetics: Maximum Plasma Concentration (Cmax) of the Analytes of ARC-520Analyte MLP75500 ng/mLStandard Deviation 6631
ARC-520 Cohort 2APharmacokinetics: Maximum Plasma Concentration (Cmax) of the Analytes of ARC-520Analyte AD001046220 ng/mLStandard Deviation 5497
ARC-520 Cohort 2Pharmacokinetics: Maximum Plasma Concentration (Cmax) of the Analytes of ARC-520Analyte AD001049233 ng/mLStandard Deviation 7088
ARC-520 Cohort 2Pharmacokinetics: Maximum Plasma Concentration (Cmax) of the Analytes of ARC-520Analyte AD000956350 ng/mLStandard Deviation 7516
ARC-520 Cohort 2Pharmacokinetics: Maximum Plasma Concentration (Cmax) of the Analytes of ARC-520Analyte MLP85467 ng/mLStandard Deviation 9382
ARC-520 Cohort 3Pharmacokinetics: Maximum Plasma Concentration (Cmax) of the Analytes of ARC-520Analyte AD000973017 ng/mLStandard Deviation 8532
ARC-520 Cohort 3Pharmacokinetics: Maximum Plasma Concentration (Cmax) of the Analytes of ARC-520Analyte MLP112050 ng/mLStandard Deviation 13863
ARC-520 Cohort 3Pharmacokinetics: Maximum Plasma Concentration (Cmax) of the Analytes of ARC-520Analyte AD001064033 ng/mLStandard Deviation 8944
Secondary

Pharmacokinetics: Terminal Elimination Rate Constant (Lambda z) of the Analytes of ARC-520

Analytes include AD0009 and AD0010 (cholesterol-conjugated siRNA targeting HBV) and MLP.

Time frame: Day 1 pre-dose through 48 hours post-dose

Population: All participants with highest achievable infusion rate up to a slow bolus push (Cohort 6) and all participants receiving 4.0, 5.0 and 6.0 mg/kg using an infusion rate of 0.9 mL/min (Cohorts 3, 7 and 8) who had at least one PK sample collected

ArmMeasureGroupValue (MEAN)Dispersion
ARC-520 Cohort 1Pharmacokinetics: Terminal Elimination Rate Constant (Lambda z) of the Analytes of ARC-520Analyte AD00090.170 1/hrStandard Deviation 0.027
ARC-520 Cohort 1Pharmacokinetics: Terminal Elimination Rate Constant (Lambda z) of the Analytes of ARC-520Analyte MLP0.068 1/hrStandard Deviation 0.015
ARC-520 Cohort 1Pharmacokinetics: Terminal Elimination Rate Constant (Lambda z) of the Analytes of ARC-520Analyte AD00100.150 1/hrStandard Deviation 0.027
ARC-520 Cohort 2APharmacokinetics: Terminal Elimination Rate Constant (Lambda z) of the Analytes of ARC-520Analyte AD00090.170 1/hrStandard Deviation 0.012
ARC-520 Cohort 2APharmacokinetics: Terminal Elimination Rate Constant (Lambda z) of the Analytes of ARC-520Analyte MLP0.070 1/hrStandard Deviation 0.022
ARC-520 Cohort 2APharmacokinetics: Terminal Elimination Rate Constant (Lambda z) of the Analytes of ARC-520Analyte AD00100.134 1/hrStandard Deviation 0.025
ARC-520 Cohort 2Pharmacokinetics: Terminal Elimination Rate Constant (Lambda z) of the Analytes of ARC-520Analyte AD00100.140 1/hrStandard Deviation 0.022
ARC-520 Cohort 2Pharmacokinetics: Terminal Elimination Rate Constant (Lambda z) of the Analytes of ARC-520Analyte AD00090.172 1/hrStandard Deviation 0.019
ARC-520 Cohort 2Pharmacokinetics: Terminal Elimination Rate Constant (Lambda z) of the Analytes of ARC-520Analyte MLP0.057 1/hrStandard Deviation 0.008
ARC-520 Cohort 3Pharmacokinetics: Terminal Elimination Rate Constant (Lambda z) of the Analytes of ARC-520Analyte AD00090.155 1/hrStandard Deviation 0.021
ARC-520 Cohort 3Pharmacokinetics: Terminal Elimination Rate Constant (Lambda z) of the Analytes of ARC-520Analyte MLP0.058 1/hrStandard Deviation 0.013
ARC-520 Cohort 3Pharmacokinetics: Terminal Elimination Rate Constant (Lambda z) of the Analytes of ARC-520Analyte AD00100.117 1/hrStandard Deviation 0.023

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026