Trial Outcomes & Findings for A Study of ARC-AAT in Healthy Volunteer Subjects and Patients With Alpha-1 Antitrypsin Deficiency (AATD) (NCT NCT02363946)

NCT ID: NCT02363946

Last Updated: 2026-01-12

Results Overview

An adverse event (AE) is defined as any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as defined as AEs with onset after administration of the study drug, or when a preexisting medical condition increases in severity or frequency after study drug administration. SAEs are defined as is an 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; is a medically important event or reaction.

• Recruitment status: TERMINATED
• Study phase: PHASE1
• Target enrollment: 65 participants
• Primary outcome timeframe: From the first dose of study treatment through Day 29 ± 1 day
• Results posted on: 2026-01-12

Participant Flow

This study terminated early and no participants were enrolled in the 6.0 mg/kg and 7.0 mg/kg arms planned in Part B.

Participant milestones

Measure	Part A: 0.38 mg/kg Single dose administration of ARC-AAT intravenous (IV) injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with alpha-1 antitrypsin deficiency (AATD)	Part B: 4.0 mg/kg Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo Single dose administration of 0.9% normal saline IV injection in participants with AATD
Overall Study STARTED	4	4	4	4	4	4	4	4	4	18	4	3	4
Overall Study COMPLETED	4	4	4	4	4	4	4	3	4	18	4	3	4
Overall Study NOT COMPLETED	0	0	0	0	0	0	0	1	0	0	0	0	0

Reasons for withdrawal

Measure	Part A: 0.38 mg/kg Single dose administration of ARC-AAT intravenous (IV) injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with alpha-1 antitrypsin deficiency (AATD)	Part B: 4.0 mg/kg Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo Single dose administration of 0.9% normal saline IV injection in participants with AATD
Overall Study Lost to Follow-up	0	0	0	0	0	0	0	1	0	0	0	0	0

Baseline Characteristics

A Study of ARC-AAT in Healthy Volunteer Subjects and Patients With Alpha-1 Antitrypsin Deficiency (AATD)

Baseline characteristics by cohort

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo n=18 Participants Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with alpha-1 antitrypsin deficiency (AATD)	Part B: 4.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo n=4 Participants Single dose administration of 0.9% normal saline IV injection in participants with AATD	Total n=65 Participants Total of all reporting groups
Age, Continuous	39.0 years STANDARD_DEVIATION 9.8 • n=210 Participants	25.0 years STANDARD_DEVIATION 4.5 • n=19 Participants	30.0 years STANDARD_DEVIATION 7.8 • n=8 Participants	29.5 years STANDARD_DEVIATION 10.7 • n=24 Participants	32.3 years STANDARD_DEVIATION 5.6 • n=5716 Participants	23.8 years STANDARD_DEVIATION 4.1 • n=47026 Participants	32.5 years STANDARD_DEVIATION 15.3 • n=66536 Participants	26.0 years STANDARD_DEVIATION 5.0 • n=335 Participants	25.0 years STANDARD_DEVIATION 1.8 • n=451 Participants	25.4 years STANDARD_DEVIATION 4.8 • n=6 Participants	59.0 years STANDARD_DEVIATION 1.8 • n=77 Participants	64.3 years STANDARD_DEVIATION 3.8 • n=6 Participants	58.8 years STANDARD_DEVIATION 9.0 • n=63 Participants	33.4 years STANDARD_DEVIATION 14.3 • n=6 Participants
Sex: Female, Male Female	1 Participants n=210 Participants	4 Participants n=19 Participants	2 Participants n=8 Participants	1 Participants n=24 Participants	1 Participants n=5716 Participants	4 Participants n=47026 Participants	3 Participants n=66536 Participants	3 Participants n=335 Participants	2 Participants n=451 Participants	12 Participants n=6 Participants	3 Participants n=77 Participants	1 Participants n=6 Participants	3 Participants n=63 Participants	40 Participants n=6 Participants
Sex: Female, Male Male	3 Participants n=210 Participants	0 Participants n=19 Participants	2 Participants n=8 Participants	3 Participants n=24 Participants	3 Participants n=5716 Participants	0 Participants n=47026 Participants	1 Participants n=66536 Participants	1 Participants n=335 Participants	2 Participants n=451 Participants	6 Participants n=6 Participants	1 Participants n=77 Participants	2 Participants n=6 Participants	1 Participants n=63 Participants	25 Participants n=6 Participants

PRIMARY outcome

Timeframe: From the first dose of study treatment through Day 29 ± 1 day

Population: All participants receiving at least 1 dose of study medication

An adverse event (AE) is defined as any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as defined as AEs with onset after administration of the study drug, or when a preexisting medical condition increases in severity or frequency after study drug administration. SAEs are defined as is an 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; is a medically important event or reaction.

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo n=18 Participants Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo n=4 Participants Single dose administration of 0.9% normal saline IV injection in participants with AATD
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs TEAEs	2 participants	2 participants	2 participants	1 participants	3 participants	3 participants	3 participants	1 participants	3 participants	9 participants	3 participants	2 participants	4 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs Study Drug Related TEAEs	1 participants	1 participants	2 participants	1 participants	1 participants	2 participants	0 participants	0 participants	3 participants	1 participants	1 participants	0 participants	0 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs Severe TEAEs	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs Mild or Moderate TEAEs	2 participants	2 participants	2 participants	1 participants	3 participants	3 participants	3 participants	1 participants	3 participants	8 participants	3 participants	2 participants	4 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs Study Drug Related Moderate TEAEs	1 participants	0 participants	1 participants	1 participants	0 participants	0 participants	0 participants	0 participants	3 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs Study Drug Related Severe TEAEs	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs SAEs	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs Discontinuations Due to TEAEs	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Day 1 through Day 29 ± 1 day

Population: All participants receiving at least 1 dose of study medication

Laboratory values collected include: hematology (haemoglobin, lymphocytes, neutrophils, platelets, white cell count, monocytes); biochemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, creatine kinase, creatinine, gamma-glutamyltransferase, fasting glucose, troponin I); coagulation parameters (fibrinogen, international normalized ratio); and C-reactive protein.

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo n=18 Participants Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo n=4 Participants Single dose administration of 0.9% normal saline IV injection in participants with AATD
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values Red Cell Distribution Width	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values Neutrophils	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values Troponin I	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values Creatine Kinase	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values White Cell Count	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values Monocytes	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Day 1 through Day 29 ± 1 day

Population: All participants receiving at least 1 dose of study medication

Values collected include: vital signs (clinically concerning or symptomatic treatment emergent changes in heart rate, systolic blood pressure, diastolic blood pressure, respiratory rate, or temperature); ECGs (clinically significant changes from baseline were observed for ventricular rate, RR interval, QRS duration, QT interval or QT interval corrected for heart rate using Fridericia's formula [QTcF]; treatment emergent clinically significant changes in ST segments, P wave or T wave morphology; cardiac telemetry monitoring); clinically significant abnormal physical examination findings; treatment emergent sensitivity to bee venom; pulmonary function (clinically significant worsening in spirometry parameters and carbon monoxide diffusing capacity of the lung for carbon monoxide [DLCO]).

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo n=18 Participants Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo n=4 Participants Single dose administration of 0.9% normal saline IV injection in participants with AATD
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations Vital Signs	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations ECGs	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations Physical Examination Findings	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	1 participants	0 participants
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations Bee Venom Sensitivity	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations Pulmonary Function	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose

Population: Per protocol pharmacokinetic analysis set: all participants with evaluable concentration time profiles for each dose level who had no major protocol violations

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo Single dose administration of 0.9% normal saline IV injection in participants with AATD
Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) Analyte AD00370	4430 ng/mL Standard Deviation 1175	15500 ng/mL Standard Deviation 2811	32400 ng/mL Standard Deviation 7005	50650 ng/mL Standard Deviation 7461	75625 ng/mL Standard Deviation 8152	93275 ng/mL Standard Deviation 6133	115750 ng/mL Standard Deviation 11871	130250 ng/mL Standard Deviation 14127	167000 ng/mL Standard Deviation 7810	—	—	—	—
Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) Analyte ARC-MLP	2760 ng/mL Standard Deviation 508	9350 ng/mL Standard Deviation 2368	20700 ng/mL Standard Deviation 3334	27050 ng/mL Standard Deviation 5390	43425 ng/mL Standard Deviation 3872	48975 ng/mL Standard Deviation 5590	70050 ng/mL Standard Deviation 6946	62525 ng/mL Standard Deviation 4029	84733 ng/mL Standard Deviation 2875	—	—	—	—

PRIMARY outcome

Timeframe: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose

Population: Per protocol pharmacokinetic analysis set: all participants with evaluable concentration time profiles for each dose level who had no major protocol violations

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo Single dose administration of 0.9% normal saline IV injection in participants with AATD
Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A) Analyte AD00370	0.083 hour Interval 0.083 to 0.25	0.083 hour Interval 0.083 to 0.083	0.083 hour Interval 0.083 to 0.083	0.083 hour Interval 0.083 to 0.5	0.083 hour Interval 0.083 to 0.083	0.083 hour Interval 0.083 to 0.5	0.083 hour Interval 0.083 to 0.5	0.083 hour Interval 0.083 to 0.5	0.50 hour Interval 0.083 to 0.5	—	—	—	—
Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A) Analyte ARC-MLP	0.083 hour Interval 0.083 to 0.25	0.083 hour Interval 0.083 to 0.083	0.083 hour Interval 0.083 to 0.083	0.083 hour Interval 0.083 to 0.083	0.083 hour Interval 0.083 to 0.5	0.083 hour Interval 0.083 to 0.5	0.083 hour Interval 0.083 to 1.0	0.50 hour Interval 0.083 to 1.0	0.50 hour Interval 0.5 to 0.5	—	—	—	—

PRIMARY outcome

Timeframe: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose

Population: Per protocol pharmacokinetic analysis set: all participants with evaluable concentration time profiles for each dose level who had no major protocol violations

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo Single dose administration of 0.9% normal saline IV injection in participants with AATD
Pharmacokinetics of ARC-AAT: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Time 24 Hours (AUC0-24) for the Analytes AD00370 and ARC-MLP (Part A) Analyte AD00370	26905 hr*ng/mL Standard Deviation 10793	85138 hr*ng/mL Standard Deviation 12234	162198 hr*ng/mL Standard Deviation 56129	282710 hr*ng/mL Standard Deviation 61810	438532 hr*ng/mL Standard Deviation 38111	541628 hr*ng/mL Standard Deviation 49787	708648 hr*ng/mL Standard Deviation 212442	763392 hr*ng/mL Standard Deviation 96095	908117 hr*ng/mL Standard Deviation 144892	—	—	—	—
Pharmacokinetics of ARC-AAT: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Time 24 Hours (AUC0-24) for the Analytes AD00370 and ARC-MLP (Part A) Analyte ARC-MLP	28734 hr*ng/mL Standard Deviation 6757	82627 hr*ng/mL Standard Deviation 32332	213250 hr*ng/mL Standard Deviation 67886	291876 hr*ng/mL Standard Deviation 58240	458790 hr*ng/mL Standard Deviation 48790	459939 hr*ng/mL Standard Deviation 81820	699833 hr*ng/mL Standard Deviation 85172	716938 hr*ng/mL Standard Deviation 46783	1011569 hr*ng/mL Standard Deviation 101693	—	—	—	—

PRIMARY outcome

Timeframe: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose

Population: Per protocol pharmacokinetic analysis set: all participants with evaluable concentration time profiles for each dose level who had no major protocol violations

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo Single dose administration of 0.9% normal saline IV injection in participants with AATD
Pharmacokinetics of ARC-AAT: Area Under the Plasma Concentration Versus Time Curve From From Zero to Infinity (AUCinf) for the Analytes AD00370 and ARC-MLP (Part A) Analyte AD00370	27388 hr*ng/mL Standard Deviation 11183	85906 hr*ng/mL Standard Deviation 12529	164856 hr*ng/mL Standard Deviation 58070	285487 hr*ng/mL Standard Deviation 62310	441239 hr*ng/mL Standard Deviation 39032	547045 hr*ng/mL Standard Deviation 52126	719843 hr*ng/mL Standard Deviation 226599	771924 hr*ng/mL Standard Deviation 100469	916343 hr*ng/mL Standard Deviation 147924	—	—	—	—
Pharmacokinetics of ARC-AAT: Area Under the Plasma Concentration Versus Time Curve From From Zero to Infinity (AUCinf) for the Analytes AD00370 and ARC-MLP (Part A) Analyte ARC-MLP	34718 hr*ng/mL Standard Deviation 8345	103116 hr*ng/mL Standard Deviation 48837	277684 hr*ng/mL Standard Deviation 119873	380506 hr*ng/mL Standard Deviation 89117	559372 hr*ng/mL Standard Deviation 82769	569056 hr*ng/mL Standard Deviation 129569	872798 hr*ng/mL Standard Deviation 136277	952668 hr*ng/mL Standard Deviation 99324	1251318 hr*ng/mL Standard Deviation 138571	—	—	—	—

PRIMARY outcome

Timeframe: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose

Population: Per protocol pharmacokinetic analysis set: all participants with evaluable concentration time profiles for each dose level who had no major protocol violations

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo Single dose administration of 0.9% normal saline IV injection in participants with AATD
Pharmacokinetics of ARC-AAT: Terminal Elimination Rate Constant Obtained From the Slope of the Line (Kel) for the Analytes AD00370 and ARC-MLP (Part A) Analyte AD00370	0.186 1/hour Standard Deviation 0.050	0.177 1/hour Standard Deviation 0.004	0.170 1/hour Standard Deviation 0.013	0.174 1/hour Standard Deviation 0.004	0.185 1/hour Standard Deviation 0.011	0.183 1/hour Standard Deviation 0.006	0.185 1/hour Standard Deviation 0.023	0.178 1/hour Standard Deviation 0.010	0.181 1/hour Standard Deviation 0.009	—	—	—	—
Pharmacokinetics of ARC-AAT: Terminal Elimination Rate Constant Obtained From the Slope of the Line (Kel) for the Analytes AD00370 and ARC-MLP (Part A) Analyte ARC-MLP	0.0786 1/hour Standard Deviation 0.0141	0.0879 1/hour Standard Deviation 0.0297	0.0778 1/hour Standard Deviation 0.0265	0.0762 1/hour Standard Deviation 0.0218	0.0846 1/hour Standard Deviation 0.0158	0.0815 1/hour Standard Deviation 0.0231	0.0768 1/hour Standard Deviation 0.0104	0.0622 1/hour Standard Deviation 0.0077	0.0730 1/hour Standard Deviation 0.0046	—	—	—	—

PRIMARY outcome

Timeframe: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose

Population: Per protocol pharmacokinetic analysis set: all participants with evaluable concentration time profiles for each dose level who had no major protocol violations

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo Single dose administration of 0.9% normal saline IV injection in participants with AATD
Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) Analyte AD00370	3.90 hours Standard Deviation 0.84	3.91 hours Standard Deviation 0.09	4.09 hours Standard Deviation 0.31	3.99 hours Standard Deviation 0.09	3.75 hours Standard Deviation 0.22	3.78 hours Standard Deviation 0.12	3.80 hours Standard Deviation 0.53	3.90 hours Standard Deviation 0.23	3.83 hours Standard Deviation 0.19	—	—	—	—
Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) Analyte ARC-MLP	9.02 hours Standard Deviation 1.50	8.60 hours Standard Deviation 2.88	9.77 hours Standard Deviation 3.39	9.83 hours Standard Deviation 3.46	8.43 hours Standard Deviation 1.68	8.93 hours Standard Deviation 1.98	9.17 hours Standard Deviation 1.40	11.3 hours Standard Deviation 1.5	9.52 hours Standard Deviation 0.61	—	—	—	—

PRIMARY outcome

Timeframe: Baseline, Days 3, 8, 15, 22 and 29

Population: All participants who received a full dose of study drug with evaluable data at given time point.

Clinical assay for total serum AAT level was used for Part A. A quantitative measurement of AAT was used for Part B. A negative percent reduction indicates a percentage increase. Baseline AAT levels consisted of a geometric mean based on 3 assessments taken prior to study drug administration: at 2 time points during the Screening window at least 5 days apart, and on Day -1.

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo n=18 Participants Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo n=4 Participants Single dose administration of 0.9% normal saline IV injection in participants with AATD
Percentage Reduction From Baseline of AAT Up to Day 29 Day 3	-4.70 percentage reduction Standard Deviation 8.45	-7.00 percentage reduction Standard Deviation 3.19	-1.94 percentage reduction Standard Deviation 4.49	13.76 percentage reduction Standard Deviation 4.74	20.76 percentage reduction Standard Deviation 5.86	21.65 percentage reduction Standard Deviation 5.28	22.20 percentage reduction Standard Deviation 8.80	20.35 percentage reduction Standard Deviation 11.83	30.07 percentage reduction Standard Deviation 6.37	-4.65 percentage reduction Standard Deviation 11.13	11.5 percentage reduction Standard Deviation 11.5	43.8 percentage reduction Standard Deviation 5.6	-13.0 percentage reduction Standard Deviation 31.9
Percentage Reduction From Baseline of AAT Up to Day 29 Day 8	0.93 percentage reduction Standard Deviation 2.86	10.90 percentage reduction Standard Deviation 8.30	13.40 percentage reduction Standard Deviation 11.68	33.20 percentage reduction Standard Deviation 14.33	46.92 percentage reduction Standard Deviation 6.16	58.52 percentage reduction Standard Deviation 6.15	58.44 percentage reduction Standard Deviation 7.50	50.95 percentage reduction Standard Deviation 6.82	58.66 percentage reduction Standard Deviation 2.99	-0.26 percentage reduction Standard Deviation 10.80	43.1 percentage reduction Standard Deviation 26.7	54.4 percentage reduction Standard Deviation 22.2	7.0 percentage reduction Standard Deviation 36.9
Percentage Reduction From Baseline of AAT Up to Day 29 Day 15	5.00 percentage reduction Standard Deviation 2.62	3.89 percentage reduction Standard Deviation 2.78	26.72 percentage reduction Standard Deviation 14.31	33.65 percentage reduction Standard Deviation 14.66	61.53 percentage reduction Standard Deviation 11.75	74.20 percentage reduction Standard Deviation 7.03	75.75 percentage reduction Standard Deviation 5.95	73.57 percentage reduction Standard Deviation 2.76	79.18 percentage reduction Standard Deviation 4.03	0.78 percentage reduction Standard Deviation 11.91	37.5 percentage reduction Standard Deviation 20.4	77.7 percentage reduction Standard Deviation 1.5	7.2 percentage reduction Standard Deviation 19.8
Percentage Reduction From Baseline of AAT Up to Day 29 Day 22	1.42 percentage reduction Standard Deviation 4.01	6.81 percentage reduction Standard Deviation 8.81	15.59 percentage reduction Standard Deviation 9.21	35.50 percentage reduction Standard Deviation 15.24	58.64 percentage reduction Standard Deviation 13.55	77.18 percentage reduction Standard Deviation 9.94	83.12 percentage reduction Standard Deviation 3.67	81.14 percentage reduction Standard Deviation 1.17	87.47 percentage reduction Standard Deviation 2.09	0.50 percentage reduction Standard Deviation 13.48	25.1 percentage reduction Standard Deviation 17.2	59.5 percentage reduction Standard Deviation 13.4	1.7 percentage reduction Standard Deviation 20.8
Percentage Reduction From Baseline of AAT Up to Day 29 Day 29	0.19 percentage reduction Standard Deviation 10.37	25.87 percentage reduction Standard Deviation 6.58	13.93 percentage reduction Standard Deviation 17.16	27.40 percentage reduction Standard Deviation 10.65	50.02 percentage reduction Standard Deviation 20.46	73.15 percentage reduction Standard Deviation 14.46	82.99 percentage reduction Standard Deviation 4.19	78.20 percentage reduction Standard Deviation 7.83	87.93 percentage reduction Standard Deviation 1.75	-1.56 percentage reduction Standard Deviation 8.66	21.0 percentage reduction Standard Deviation 24.4	65.2 percentage reduction Standard Deviation 8.7	-7.2 percentage reduction Standard Deviation 30.3

SECONDARY outcome

Timeframe: Baseline, Days 3, 8, 15, 22 and 29

Population: All participants who received a full dose of study drug with evaluable data at given time point.

Data presents the study visit day upon which a participant had the first occurrence of AAT reduction of > 30% from Baseline, and the number of participants who had a > 30% reduction at any visit (overall). Baseline AAT levels consisted of a geometric mean based on 3 assessments taken prior to study drug administration: at 2 time points during the Screening window at least 5 days apart, and on Day -1.

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo n=18 Participants Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo n=4 Participants Single dose administration of 0.9% normal saline IV injection in participants with AATD
Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) Overall	0 participants	2 participants	2 participants	3 participants	4 participants	4 participants	4 participants	4 participants	3 participants	0 participants	2 participants	3 participants	1 participants
Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) Day 3	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	1 participants	2 participants	0 participants	0 participants	3 participants	0 participants
Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) Day 8	0 participants	0 participants	0 participants	1 participants	4 participants	4 participants	3 participants	2 participants	1 participants	0 participants	2 participants	0 participants	1 participants
Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) Day 15	0 participants	0 participants	2 participants	2 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) Day 22	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) Day 29	0 participants	2 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Study Day for Nadir of Mean AAT: Day 8 (for Part B 2 mg/kg arm), Day 15 (for Part A 0.38 mg/kg, 2 mg/kg, 4 mg/ kg, Placebo arms; Part B 4 mg/kg, Placebo arms), Day 22 (Part A 3 mg/kg, 5 mg/kg, 6 mg/kg, 7 mg/kg arms), Day 29 (1 mg/kg, 8 mg/kg arms)

Population: All participants who received a full dose of study drug.

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo n=18 Participants Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo n=4 Participants Single dose administration of 0.9% normal saline IV injection in participants with AATD
Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT)	5.0 percentage reduction	25.9 percentage reduction	26.7 percentage reduction	35.5 percentage reduction	61.5 percentage reduction	77.2 percentage reduction	83.1 percentage reduction	81.1 percentage reduction	87.9 percentage reduction	0.78 percentage reduction	43.1 percentage reduction	77.7 percentage reduction	7.2 percentage reduction

SECONDARY outcome

Timeframe: Baseline, up to Day 29, and through 100 days of follow-up

Population: All participants

Baseline AAT levels consisted of a geometric mean based on 3 assessments taken prior to study drug administration: at 2 time points during the Screening window at least 5 days apart, and on Day -1.

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo n=18 Participants Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg n=3 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo n=4 Participants Single dose administration of 0.9% normal saline IV injection in participants with AATD
Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days	4 participants	4 participants	4 participants	4 participants	4 participants	4 participants	4 participants	4 participants	4 participants	18 participants	4 participants	3 participants	4 participants

SECONDARY outcome

Timeframe: Pre-dose, 2 hours post-dose

Population: Participants with available data for given parameter.

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo n=18 Participants Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg n=1 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo n=3 Participants Single dose administration of 0.9% normal saline IV injection in participants with AATD
Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose Serum interleukin-1 beta	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	-9 percentage change Standard Deviation 17	9 percentage change Standard Deviation 18	0 percentage change Standard Deviation 0	-2 percentage change Standard Deviation 10	114 percentage change Standard Deviation NA only 1 participant evaluated	0 percentage change Standard Deviation 0
Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose Serum interleukin-6	5 percentage change Standard Deviation 8	79 percentage change Standard Deviation 141	95 percentage change Standard Deviation 113	50 percentage change Standard Deviation 64	277 percentage change Standard Deviation 308	100 percentage change Standard Deviation 191	146 percentage change Standard Deviation 261	258 percentage change Standard Deviation 285	364 percentage change Standard Deviation 255	-1 percentage change Standard Deviation 7	60 percentage change Standard Deviation 52	130 percentage change Standard Deviation NA only 1 participant evaluated	56 percentage change Standard Deviation 91
Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose Serum interleukin-8	32 percentage change Standard Deviation 70	280 percentage change Standard Deviation 328	336 percentage change Standard Deviation 297	103 percentage change Standard Deviation 101	1712 percentage change Standard Deviation 981	564 percentage change Standard Deviation 576	252 percentage change Standard Deviation 363	695 percentage change Standard Deviation 635	2015 percentage change Standard Deviation 1569	-6 percentage change Standard Deviation 17	197 percentage change Standard Deviation 319	46 percentage change Standard Deviation NA only 1 participant evaluated	-44 percentage change Standard Deviation 13
Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose Serum interleukin-10	-5 percentage change Standard Deviation 19	72 percentage change Standard Deviation 134	51 percentage change Standard Deviation 52	42 percentage change Standard Deviation 45	27 percentage change Standard Deviation 54	19 percentage change Standard Deviation 28	116 percentage change Standard Deviation 160	377 percentage change Standard Deviation 498	638 percentage change Standard Deviation 536	-2 percentage change Standard Deviation 7	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation NA only 1 participant evaluated	-5 percentage change Standard Deviation 8
Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose Serum interleukin-12p40	2 percentage change Standard Deviation 37	2 percentage change Standard Deviation 5	5 percentage change Standard Deviation 8	6 percentage change Standard Deviation 9	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	152 percentage change Standard Deviation 217	-9 percentage change Standard Deviation 19	29 percentage change Standard Deviation 38	-3 percentage change Standard Deviation 10	-4 percentage change Standard Deviation 13	79 percentage change Standard Deviation NA only 1 participant evaluated	0 percentage change Standard Deviation 0
Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose Serum interleukin-12p70	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	54 percentage change Standard Deviation 108	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	166 percentage change Standard Deviation 389	82 percentage change Standard Deviation 130	-1 percentage change Standard Deviation 4	-3 percentage change Standard Deviation 5	48 percentage change Standard Deviation NA only 1 participant evaluated	23 percentage change Standard Deviation 40
Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose Serum monocyte chemoattractant protein-1	123 percentage change Standard Deviation 171	442 percentage change Standard Deviation 133	505 percentage change Standard Deviation 254	632 percentage change Standard Deviation 281	1176 percentage change Standard Deviation 427	1297 percentage change Standard Deviation 747	543 percentage change Standard Deviation 497	906 percentage change Standard Deviation 720	2014 percentage change Standard Deviation 427	1 percentage change Standard Deviation 13	262 percentage change Standard Deviation 262	44 percentage change Standard Deviation NA only 1 participant evaluated	-27 percentage change Standard Deviation 14
Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose Serum macrophage inflammatory protein-1 alpha	147 percentage change Standard Deviation 126	294 percentage change Standard Deviation 275	386 percentage change Standard Deviation 556	264 percentage change Standard Deviation 438	1674 percentage change Standard Deviation 1022	1096 percentage change Standard Deviation 578	406 percentage change Standard Deviation 416	1003 percentage change Standard Deviation 814	854 percentage change Standard Deviation 538	15 percentage change Standard Deviation 69	246 percentage change Standard Deviation 304	0 percentage change Standard Deviation NA only 1 participant evaluated	0 percentage change Standard Deviation 0
Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose Serum tumor necrosis factor alpha	66 percentage change Standard Deviation 69	207 percentage change Standard Deviation 90	286 percentage change Standard Deviation 90	187 percentage change Standard Deviation 156	818 percentage change Standard Deviation 344	476 percentage change Standard Deviation 137	301 percentage change Standard Deviation 237	761 percentage change Standard Deviation 492	742 percentage change Standard Deviation 273	3 percentage change Standard Deviation 27	107 percentage change Standard Deviation 152	55 percentage change Standard Deviation NA only 1 participant evaluated	-29 percentage change Standard Deviation 11
Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose Serum interferon alpha 2	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	0 percentage change Standard Deviation 0	4 percentage change Standard Deviation 7	73 percentage change Standard Deviation 147	172 percentage change Standard Deviation 366	515 percentage change Standard Deviation 529	5 percentage change Standard Deviation 20	-3 percentage change Standard Deviation 7	700 percentage change Standard Deviation NA only 1 participant evaluated	69 percentage change Standard Deviation 119

SECONDARY outcome

Timeframe: Pre-dose, 2 hours post-dose

Population: Participants with available data for given parameter.

Outcome measures

Measure	Part A: 0.38 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo n=18 Participants Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg n=4 Participants Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg n=1 Participants Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo n=3 Participants Single dose administration of 0.9% normal saline IV injection in participants with AATD
Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose Serum C4a	-5 percentage change Standard Deviation 7	37 percentage change Standard Deviation 70	-11 percentage change Standard Deviation 10	2 percentage change Standard Deviation 8	16 percentage change Standard Deviation 13	-8 percentage change Standard Deviation 27	78 percentage change Standard Deviation 107	60 percentage change Standard Deviation 53	-1 percentage change Standard Deviation 15	-19 percentage change Standard Deviation 35	-35 percentage change Standard Deviation 21	160 percentage change Standard Deviation NA only 1 participant evaluated	-15 percentage change Standard Deviation 42
Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose Serum C5a	2 percentage change Standard Deviation 7	2 percentage change Standard Deviation 7	-16 percentage change Standard Deviation 5	-2 percentage change Standard Deviation 25	-14 percentage change Standard Deviation 7	2 percentage change Standard Deviation 15	0 percentage change Standard Deviation 8	6 percentage change Standard Deviation 6	6 percentage change Standard Deviation 12	-2 percentage change Standard Deviation 18	-4 percentage change Standard Deviation 16	22 percentage change Standard Deviation NA only 1 participant evaluated	-4 percentage change Standard Deviation 10
Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose Serum CH50	-5 percentage change Standard Deviation 8	-14 percentage change Standard Deviation 11	-14 percentage change Standard Deviation 7	-8 percentage change Standard Deviation 8	-16 percentage change Standard Deviation 4	-17 percentage change Standard Deviation 8	-10 percentage change Standard Deviation 4	-13 percentage change Standard Deviation 13	-19 percentage change Standard Deviation 10	-3 percentage change Standard Deviation 9	-3 percentage change Standard Deviation 3	-18 percentage change Standard Deviation NA only 1 participant evaluated	-0 percentage change Standard Deviation 13
Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose Plasma Bb	18 percentage change Standard Deviation 16	56 percentage change Standard Deviation 25	76 percentage change Standard Deviation 37	133 percentage change Standard Deviation 29	181 percentage change Standard Deviation 185	137 percentage change Standard Deviation 85	70 percentage change Standard Deviation 63	147 percentage change Standard Deviation 73	309 percentage change Standard Deviation 174	-7 percentage change Standard Deviation 9	56 percentage change Standard Deviation 61	59 percentage change Standard Deviation NA only 1 participant evaluated	-14 percentage change Standard Deviation 7
Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose Serum C3a	-12 percentage change Standard Deviation 6	30 percentage change Standard Deviation 42	-22 percentage change Standard Deviation 24	-0 percentage change Standard Deviation 8	71 percentage change Standard Deviation 156	-5 percentage change Standard Deviation 18	14 percentage change Standard Deviation 56	40 percentage change Standard Deviation 50	34 percentage change Standard Deviation 30	-11 percentage change Standard Deviation 23	-18 percentage change Standard Deviation 23	219 percentage change Standard Deviation NA only 1 participant evaluated	16 percentage change Standard Deviation 40

Adverse Events

Part A: 0.38 mg/kg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A: 1.0 mg/kg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A: 2.0 mg/kg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A: 3.0 mg/kg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part A: 4.0 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A: 5.0 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A: 6.0 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A: 7.0 mg/kg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part A: 8.0 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A: Placebo

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Part B: 2.0 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part B: 4.0 mg/kg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part B: Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part A: 0.38 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo n=18 participants at risk Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg n=3 participants at risk Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo n=4 participants at risk Single dose administration of 0.9% normal saline IV injection in participants with AATD
Musculoskeletal and connective tissue disorders Rhabdomyolosis	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	5.6% 1/18 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day

Other adverse events

Measure	Part A: 0.38 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers	Part A: 1.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers	Part A: 2.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers	Part A: 3.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers	Part A: 4.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers	Part A: 5.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers	Part A: 6.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers	Part A: 7.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers	Part A: 8.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers	Part A: Placebo n=18 participants at risk Single dose administration of 0.9% normal saline IV injection in healthy volunteers	Part B: 2.0 mg/kg n=4 participants at risk Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD	Part B: 4.0 mg/kg n=3 participants at risk Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD	Part B: Placebo n=4 participants at risk Single dose administration of 0.9% normal saline IV injection in participants with AATD
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	33.3% 1/3 • Number of events 1 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day
Gastrointestinal disorders Diarrhoea	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	33.3% 1/3 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Gastrointestinal disorders Nausea	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	33.3% 1/3 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	5.6% 1/18 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	5.6% 1/18 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Renal and urinary disorders Dysuria	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	5.6% 1/18 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
General disorders Chest discomfort	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
General disorders Chills	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	75.0% 3/4 • Number of events 3 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
General disorders Feeling cold	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
General disorders Fatigue	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	5.6% 1/18 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day
General disorders Pyrexia	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Investigations Troponin increased	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Nervous system disorders Paraesthesia	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Nervous system disorders Tremor	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Cardiac disorders Tachycardia	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Vascular disorders Peripheral coldness	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day
Infections and infestations Nasopharyngitis	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	11.1% 2/18 • Number of events 2 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Infections and infestations Upper respiratory tract infection	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	50.0% 2/4 • Number of events 2 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	5.6% 1/18 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day
Blood and lymphatic system disorders Neutropenia	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Nervous system disorders Dizziness	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	11.1% 2/18 • Number of events 2 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Nervous system disorders Headache	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	50.0% 2/4 • Number of events 2 • Day -1 through Day 29 ± 1 day	50.0% 2/4 • Number of events 2 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day
Nervous system disorders Lethargy	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	5.6% 1/18 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Nervous system disorders Migraine	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	33.3% 1/3 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Nervous system disorders Syncope	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	5.6% 1/18 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Nervous system disorders Tension headache	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	5.6% 1/18 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Infections and infestations Conjunctivitis	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	25.0% 1/4 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/18 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day
Infections and infestations Gastroenteritis viral	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	5.6% 1/18 • Number of events 1 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day	0.00% 0/3 • Day -1 through Day 29 ± 1 day	0.00% 0/4 • Day -1 through Day 29 ± 1 day

Additional Information

Chief Operating Officer

Arrowhead Pharmaceuticals, Inc.

Phone: 6263043400

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place