Hepatitis B
Conditions
Brief summary
Patients with chronic HBV infection will receive either ARC-520 or placebo in combination with entecavir or tenofovir, and be evaluated for safety and efficacy.
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled, multi-dose study of ARC-520 in combination with entecavir or tenofovir administered to patients with Hepatitis B 'e' Antigen (HBeAg) negative and immune active chronic HBV infection. Eligible patients who have signed an Ethics Committee - approved informed consent, will be enrolled and will receive ARC-520 or placebo in combination with entecavir or tenofovir. The study will enroll up to a total of 60 eligible chronic HBV infected patients. Patients 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 assessment (AEs), 12-lead electrocardiograms (ECGs), liver fibrosis testing, concomitant medication assessment, blood sample collection for hematology, coagulation,chemistry, lactate, Pharmacokinetic (PK) measures (in a subset of patients), exploratory Pharmacodynamic (PD) measures, urinalysis, HBV serology, Follicle Stimulating Hormone (FSH) testing (post-menopausal females) 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 patient is lost to follow-up. For each patient, the duration of the study is approximately 33 weeks from screening to the Day 169 follow-up visit. For patients enrolling into a planned extension study, the total duration of this study is approximately 25 weeks from screening to Day 113 end of study visit.
Interventions
ARC-520 Injection was administered concomitantly, IV with 0.9% normal saline using an infusion rate of 0.4 mL/min for study treatment and 3.6 mL/min for saline.
OTHERplacebo
Placebo was administered concomitantly, IV with 0.9% normal saline using an infusion rate of 0.4 mL/min for study treatment and 3.6 mL/min for saline.
DRUGentecavir
All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.
DRUGtenofovir
All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.
DRUGantihistamine
All participants will be pretreated with an oral antihistamine, administered 2 hours (±30 minutes) pre-dose. The antihistamine used should in general be an H1\>H2 receptor blocker and would include diphenhydramine 50 mg, cetirizine 10 mg, chlorpheniramine 8 mg or hydroxyzine 50 mg. The Investigator is free to choose any of these antihistamines available locally and consistent with their country's Marketing Authorisation.
Sponsors
Arrowhead Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, 18 to 75 years of age * Written informed consent * No clinically significant abnormalities at screening/pre-dose 12-lead ECG assessment * No new abnormal finding of clinical relevance at the screening evaluation. * Diagnosis of HBeAg negative, immune active, chronic HBV infection * \> 2 months of continuous treatment with daily, oral entecavir or tenofovir * Willingness to continue taking entecavir or tenofovir throughout the study. * Must use 2 effective methods of contraception (double barrier contraception or hormonal contraceptive along with a barrier contraceptive) (both male and female partners)
Exclusion criteria
* Pregnant or lactating * Acute signs of hepatitis/other infection within 4 weeks of screening * Antiviral therapy other than entecavir or tenofovir within 3 months of screening * Prior treatment with interferon in the last 3 years. * Use within the last 6 months or anticipated requirement for anticoagulants, corticosteroids, immunomodulators, or immunosuppressants. * Use of prescription medication within 14 days prior to treatment administration except: topical products without systemic absorption, statins (except rosuvastatin), hypertension medications, or hormonal contraceptives. * Depot injection or implant of any drug within 3 months prior to treatment administration, except injectable/implantable birth control. * Diagnosis of diabetes mellitus. * History of autoimmune disease especially autoimmune hepatitis. * Human immunodeficiency virus (HIV) infection. * Sero-positive for Hepatitis C Virus (HCV), and/or a history of delta virus hepatitis. * Hypertension defined as blood pressure \> 150/100 mmHg * History of cardiac rhythm disturbances * Family history or congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death * Symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease within 6 months prior to study entry. * History of malignancy except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. * Has had a major surgery within 3 months of screening. * History of alcohol and/or drug abuse \< 12 months from screening. * Regular uses of alcohol within 6 months prior to screening (ie, more than 14 units of alcohol per week). * Evidence of severe systemic acute inflammation, sepsis, or hemolysis. * Diagnosed with a significant psychiatric disorder. * Use of recreational drugs, such as marijuana, within 3 months prior to screening * Use of drugs such as cocaine, phencyclidine (PCP), and methamphetamines, within 1 year prior to screening. * History of allergy to bee sting. * Use of investigational agents or devices within 30 days prior to planned study dosing or current participation in an investigational study. * Clinically significant history or presence of any gastrointestinal pathology, unresolved gastrointestinal symptoms, liver or kidney disease. * Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction. * Clinically significant history or presence of poorly controlled/uncontrolled systemic disease. * History of fever within 2 weeks of screening. * Immunized with a live attenuated vaccine within 7 days prior to dosing or planned vaccination (excluding flu vaccine by injection). * Presence of any medical or psychiatric condition or social situation that impacts compliance or results in additional safety risk. * Participated in excessive exercise/physical activity within 7 days of screening or planned during the trial. * History of coagulopathy/stroke within past 6 months, and/or concurrent anticoagulant medication(s).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 113 | Baseline, Day 113 | Change From Baseline in log qHBsAg at Day 113 in response to multiple doses of ARC-520 versus placebo, using a a mixed effect model for repeated measures (MMRM). Includes parameter baseline as a continuous covariate, and treatment and visit as fixed factors, interaction of treatment and visit, and interaction of parameter baseline and visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | Through Day 169 | An 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. A treatment emergent AE (TEAE) was defined as an AE that was not present prior to the first study medication administration and started at/after the time of initiation of administration of study medication, or an AE which was present prior to initiation of study medication administration, which increased in severity after study medication administration. |
| Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) | Through 48 hours post-dosing on Day 1 and Day 85 | — |
| Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) | Through 48 hours post-dosing on Day 1 and Day 85 | — |
| Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) | Through 48 hours post-dosing on Day 1 and Day 85 | — |
| Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Baseline, Day 15, 29, 43, 57, 71, 85, 99 | Change From Baseline in log qHBsAg at Day 113 in response to multiple doses of ARC-520 versus placebo, using a a mixed effect model for repeated measures (MMRM). Includes parameter baseline as a continuous covariate, and treatment and visit as fixed factors, interaction of treatment and visit, and interaction of parameter baseline and visit. |
| Pharmacokinetics of ARC-520: Clearance (CL) | Through 48 hours post-dosing on Day 1 and Day 85 | — |
| Pharmacokinetics of ARC-520: Apparent Volume of Distribution (V) | Through 48 hours post-dosing on Day 1 and Day 85 | — |
| Pharmacokinetics of ARC-520: Terminal Elimination Rate Constant (Kel) | Through 48 hours post-dosing on Day 1 and Day 85 | — |
| Pharmacokinetics of ARC-520: Terminal Elimination Half-Life (t1/2) | Through 48 hours post-dosing on Day 1 and Day 85 | — |
| Pharmacokinetics of ARC-520: Maximum Observed Plasma Concentration (Cmax) | Through 48 hours post-dosing on Day 1 and Day 85 | — |
Countries
China, Germany, South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PBO Low Dose 0.9% normal saline, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period | 9 |
| PBO High Dose 0.9% normal saline, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period | 11 |
| ARC-520 Injection 1 mg/kg Intravenous ARC-520 at 1.0 mg/kg, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period | 17 |
| ARC-520 Injection 2 mg/kg Intravenous ARC-520 at 2.0 mg/kg, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period | 21 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Pregnancy | 0 | 0 | 0 | 1 |
| Overall Study | Study terminated by sponsor | 0 | 2 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | PBO Low Dose | PBO High Dose | ARC-520 Injection 1 mg/kg | ARC-520 Injection 2 mg/kg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 46.2 years STANDARD_DEVIATION 12.1 | 48.7 years STANDARD_DEVIATION 9.5 | 45.0 years STANDARD_DEVIATION 10.48 | 45.7 years STANDARD_DEVIATION 10.48 | 46.2 years STANDARD_DEVIATION 10.29 |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 7 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Male | 7 Participants | 10 Participants | 10 Participants | 12 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 9 | 4 / 11 | 4 / 17 | 8 / 21 |
| serious Total, serious adverse events | 0 / 9 | 0 / 11 | 2 / 17 | 1 / 21 |
Outcome results
Primary
Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 113
Change From Baseline in log qHBsAg at Day 113 in response to multiple doses of ARC-520 versus placebo, using a a mixed effect model for repeated measures (MMRM). Includes parameter baseline as a continuous covariate, and treatment and visit as fixed factors, interaction of treatment and visit, and interaction of parameter baseline and visit.
Time frame: Baseline, Day 113
Population: Intent to treat population: all participants who received at least 1 dose of study drug and had valid qHBsAg values at baseline and at least one time point on or after the Day 15 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 113 | -0.070 log IU/mL | Standard Error 0.033 |
| ARC-520 Injection 1 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 113 | -0.157 log IU/mL | Standard Error 0.036 |
| ARC-520 Injection 2 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 113 | -0.379 log IU/mL | Standard Error 0.033 |
p-value: 0.08195% CI: [-0.183, 0.011]MMRM
p-value: <0.000195% CI: [-0.406, -0.212]MMRM
p-value: <0.000195% CI: [-0.322, -0.124]MMRM
Secondary
Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time
Change From Baseline in log qHBsAg at Day 113 in response to multiple doses of ARC-520 versus placebo, using a a mixed effect model for repeated measures (MMRM). Includes parameter baseline as a continuous covariate, and treatment and visit as fixed factors, interaction of treatment and visit, and interaction of parameter baseline and visit.
Time frame: Baseline, Day 15, 29, 43, 57, 71, 85, 99
Population: Intent to treat population: all participants who received at least 1 dose of study drug and had valid qHBsAg values at baseline and at least one time point on or after the Day 15 visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 29 | 3.291 log IU/mL | Standard Error 0.694 |
| Placebo | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 71 | 3.206 log IU/mL | Standard Error 0.663 |
| Placebo | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 57 | 3.291 log IU/mL | Standard Error 0.705 |
| Placebo | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 15 | 3.297 log IU/mL | Standard Error 0.712 |
| Placebo | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 99 | 3.302 log IU/mL | Standard Error 0.7 |
| Placebo | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 85 | 3.309 log IU/mL | Standard Error 0.736 |
| Placebo | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 43 | 3.188 log IU/mL | Standard Error 0.712 |
| ARC-520 Injection 1 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 57 | 3.072 log IU/mL | Standard Error 1.061 |
| ARC-520 Injection 1 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 15 | 3.084 log IU/mL | Standard Error 1.004 |
| ARC-520 Injection 1 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 29 | 3.098 log IU/mL | Standard Error 0.986 |
| ARC-520 Injection 1 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 43 | 3.016 log IU/mL | Standard Error 1.124 |
| ARC-520 Injection 1 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 71 | 3.051 log IU/mL | Standard Error 1.029 |
| ARC-520 Injection 1 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 85 | 2.907 log IU/mL | Standard Error 0.963 |
| ARC-520 Injection 1 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 99 | 2.938 log IU/mL | Standard Error 1.055 |
| ARC-520 Injection 2 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 71 | 2.301 log IU/mL | Standard Error 0.969 |
| ARC-520 Injection 2 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 29 | 2.503 log IU/mL | Standard Error 0.846 |
| ARC-520 Injection 2 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 99 | 2.360 log IU/mL | Standard Error 0.95 |
| ARC-520 Injection 2 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 85 | 2.366 log IU/mL | Standard Error 0.862 |
| ARC-520 Injection 2 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 57 | 2.329 log IU/mL | Standard Error 0.971 |
| ARC-520 Injection 2 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 43 | 2.509 log IU/mL | Standard Error 0.836 |
| ARC-520 Injection 2 mg/kg | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time | Day 15 | 2.506 log IU/mL | Standard Error 0.844 |
Comparison: Day 15p-value: 0.058395% CI: [-0.181, 0.003]MMRM
Comparison: Day 15p-value: 0.00395% CI: [-0.267, -0.085]MMRM
Comparison: Day 15p-value: 0.06795% CI: [-0.181, 0.006]MMRM
Comparison: Day 29p-value: 0.087595% CI: [-0.151, 0.011]MMRM
Comparison: Day 29p-value: <0.000195% CI: [-0.259, -0.1]MMRM
Comparison: Day 29p-value: 0.009995% CI: [-0.191, -0.027]MMRM
Comparison: Day 43p-value: 0.001795% CI: [-0.229, -0.057]MMRM
Comparison: Day 43p-value: <0.000195% CI: [-0.349, -0.18]MMRM
Comparison: Day 43p-value: 0.007295% CI: [-0.209, -0.035]MMRM
Comparison: Day 57p-value: 0.004395% CI: [-0.197, -0.039]MMRM
Comparison: Day 57p-value: <0.000195% CI: [-0.376, -0.221]MMRM
Comparison: Day 57p-value: <0.000195% CI: [-0.261, -0.1]MMRM
Comparison: Day 71p-value: 0.008495% CI: [-0.228, -0.035]MMRM
Comparison: Day 71p-value: <0.000195% CI: [-0.433, -0.243]MMRM
Comparison: Day 71p-value: 0.000195% CI: [-0.304, -0.108]MMRM
Comparison: Day 85p-value: 0.058995% CI: [-0.195, 0.004]MMRM
Comparison: Day 85p-value: <0.000195% CI: [-0.433, -0.236]MMRM
Comparison: Day 85p-value: <0.000195% CI: [-0.34, -0.137]MMRM
Comparison: Day 99p-value: 0.013895% CI: [-0.236, -0.028]MMRM
Comparison: Day 99p-value: <0.000195% CI: [-0.458, -0.252]MMRM
Comparison: Day 99p-value: 0.000195% CI: [-0.329, -0.117]MMRM
Secondary
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs
An 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. A treatment emergent AE (TEAE) was defined as an AE that was not present prior to the first study medication administration and started at/after the time of initiation of administration of study medication, or an AE which was present prior to initiation of study medication administration, which increased in severity after study medication administration.
Time frame: Through Day 169
Population: Safety Population: all participants who received at least 1 dose of study treatment or placebo, and had at least 1 post-dose safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 TEAE Leading to Treatment Discontinuation | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 AE | 4 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 TEAE | 4 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 Serious TEAE | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | Deaths | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 TEAE Leading to Study Discontinuation | 0 Participants |
| ARC-520 Injection 1 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 TEAE Leading to Study Discontinuation | 0 Participants |
| ARC-520 Injection 1 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 Serious TEAE | 0 Participants |
| ARC-520 Injection 1 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 TEAE Leading to Treatment Discontinuation | 0 Participants |
| ARC-520 Injection 1 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 TEAE | 4 Participants |
| ARC-520 Injection 1 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 AE | 5 Participants |
| ARC-520 Injection 1 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | Deaths | 0 Participants |
| ARC-520 Injection 2 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 AE | 6 Participants |
| ARC-520 Injection 2 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 TEAE | 6 Participants |
| ARC-520 Injection 2 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 Serious TEAE | 2 Participants |
| ARC-520 Injection 2 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 TEAE Leading to Study Discontinuation | 0 Participants |
| ARC-520 Injection 2 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | Deaths | 0 Participants |
| ARC-520 Injection 2 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 TEAE Leading to Treatment Discontinuation | 0 Participants |
| ARC-520 Injection 2 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | Deaths | 0 Participants |
| ARC-520 Injection 2 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 TEAE Leading to Study Discontinuation | 0 Participants |
| ARC-520 Injection 2 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 AE | 12 Participants |
| ARC-520 Injection 2 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 Serious TEAE | 1 Participants |
| ARC-520 Injection 2 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 TEAE Leading to Treatment Discontinuation | 0 Participants |
| ARC-520 Injection 2 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs | ≥ 1 TEAE | 12 Participants |
Secondary
Pharmacokinetics of ARC-520: Apparent Volume of Distribution (V)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
Population: Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed.
Secondary
Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
Population: Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed.
Secondary
Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
Population: Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed.
Secondary
Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
Population: Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed.
Secondary
Pharmacokinetics of ARC-520: Clearance (CL)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
Population: Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed.
Secondary
Pharmacokinetics of ARC-520: Maximum Observed Plasma Concentration (Cmax)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
Population: Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed.
Secondary
Pharmacokinetics of ARC-520: Terminal Elimination Half-Life (t1/2)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
Population: Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed.
Secondary
Pharmacokinetics of ARC-520: Terminal Elimination Rate Constant (Kel)
Time frame: Through 48 hours post-dosing on Day 1 and Day 85
Population: Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed.