Alpha-1 Antitrypsin Deficiency
Conditions
Keywords
alpha-1 antitrypsin, AATD
Brief summary
The purpose of the study is to determine the safety and tolerability of escalating doses of ARC-AAT and to evaluate the pharmacokinetics of ARC-AAT and the effect of ARC-AAT on circulating levels of alpha-1 antitrypsin (AAT). The study will consist of two parts, Part A (conducted in healthy volunteers) and Part B (conducted in AATD patients) at up to 9 escalating dose levels with 6 participants per dose level.
Detailed description
Healthy volunteers and AATD patients will be randomized to receive a single intravenous injection of either ARC-AAT or Placebo in double-blind fashion. Up to thirteen cohorts (6 participants per cohort) will be enrolled. Participants in all cohorts will be confined to the clinical facility beginning on Day -1 with discharge on Day 2. Escalation to the next dose level will proceed until a participant experiences a dose-limiting toxicity (DLT) or there is achievement of pre-determined threshold reductions in AAT levels. Dosing in participants with AATD will commence based on pre-determined threshold reductions in AAT levels for healthy volunteers. For each participant, the duration of the study clinic visits is up to 11 weeks, from Screening to the End-of-Study examination. However, including a Day 90 Follow-Up telephone call, the maximum study duration is approximately 20 weeks.
Interventions
RNA interference-based, liver-targeted therapeutic
OTHERPlacebo
0.9 % normal saline
DRUGDiphenhydramine
Diphenhydramine 50 mg p.o. was administered 2 hours (±30 minutes) pre-dose as antihistamine pre-treatment.
Sponsors
Arrowhead Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
(Part A - Healthy Volunteers) * Male or female healthy volunteers 18-50 years of age * Written informed consent * Body mass index between 18.0 and 28.0 kg/m2 * 12-lead electrocardiogram (ECG) at Screening and pre-dose assessment with no clinically significant abnormalities * Non-pregnant/non-nursing females * Non-smoker for at least one year with current non-smoking status confirmed by urine cotinine * Normal lung function (or not clinically significant per investigator assessment) based on spirometry and diffusion capacity of lung for carbon monoxide (DLCO) according to American Thoracic Society (ATS) - European Respiratory Society (ERS) criteria * Highly effective, double barrier contraception (both male and female partners) during the study and for 3 months following the dose of ARC-AAT * Willing and able to comply with all study assessments and adhere to protocol schedule * Suitable venous access for blood sampling * No abnormal finding of clinical relevance at screening * Normal AAT level (Part B-Patients) - As for Part A with the following exceptions: * Male or female patients 18-70 years of age * Confirmed diagnosis of homozygous alpha 1-protease inhibitor deficiency (PiZZ genotype) not receiving alpha-1 antitrypsin augmentation therapy for more than 4 weeks * BMI between 18.0 and 35.0 kg/m2 * Non-smoker for at least three years with current non-smoking status confirmed by urine cotinine
Exclusion criteria
(Part A-Healthy Volunteers) * Current regular smoker of cigarettes or cigars or was a regular smoker over the past 1 year * Recent (within last 6 weeks) transfusion of fresh frozen plasma, platelets, or packed red blood cells, or anticipated need for transfusion during study * Acute signs of hepatitis/other infection within 4 weeks of screening and/or baseline * Concurrent anticoagulants * Use of dietary and/or herbal supplements that can interfere with liver metabolism within 7 days of screening * Use of any drugs known to induce or inhibit hepatic drug metabolism within 14 days prior to study treatment * Depot injection/implant of any drug other than birth control within 3 months prior to study treatment * Diagnosis of diabetes mellitus or history of glucose intolerance * History of poorly controlled autoimmune disease or any history of autoimmune hepatitis * Human immunodeficiency virus (HIV) infection * Seropositive for hepatitis B virus (HBV) or hepatitis C virus (HCV), and/or history of delta virus hepatitis * Uncontrolled hypertension (blood pressure \> 150/100 mmHg) * History of cardiac rhythm disturbances * Family history of congenital long QT syndrome or unexplained sudden cardiac death * Symptomatic heart failure (per New York Heart Association \[NYHA\] guidelines) * Unstable angina, myocardial infarction, severe cardiovascular disease, transient ischemic attack (TIA) or cerebrovascular accident (CVA) within past 6 months * History of malignancy within last 5 years except adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. * History of major surgery within 3 months of screening * Regular use of alcohol within 1 month prior to screening (i.e., more than fourteen units of alcohol per week) * Evidence of acute inflammation, sepsis or hemolysis or clinical evidence of lower respiratory tract infection * Diagnosis of significant psychiatric disorder * Use of illicit drugs (such as cocaine, phencyclidine \[PCP\] and crack) within 1 year prior to screening or positive urine drug screen * History of allergy or hypersensitivity reaction to bee venom * Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study * Clinically significant history/presence of any gastrointestinal pathology, unresolved gastrointestinal symptoms, liver or kidney disease * Other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs * Any clinically significant history/presence of poorly controlled neurological, endocrinal, cardiovascular, pulmonary, hematological, immunologic, psychiatric, metabolic or other uncontrolled systemic disease * Blood donation (500 mL) within 7 days prior to study treatment * History of fever within 2 weeks of screening * Concomitant medical/psychiatric condition or social situation that would affect compliance or result in additional safety risk * Excessive exercise/physical activity within 3 days of screening or enrollment or planned during the study * History of thromboembolic disease, stroke within 6 months of baseline, and/or concurrent anticoagulant medication(s) (Part B-Patients) - As for Part A with the following exceptions: * History of major surgery within 2 months of Screening * Forced expiratory volume at one second (FEV1) at baseline \< 60% * AATD patients with liver elastography score \> 11 at Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Reduction From Baseline of AAT Up to Day 29 | Baseline, Days 3, 8, 15, 22 and 29 | 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. |
| Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A) | Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose | — |
| 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) | Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose | — |
| 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) | Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose | — |
| 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) | Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose | — |
| Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose | — |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | From the first dose of study treatment through Day 29 ± 1 day | 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. |
| Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Day 1 through Day 29 ± 1 day | 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. |
| Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | Day 1 through Day 29 ± 1 day | 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 \[DLCO\]). |
| Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT) | 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) | — |
| Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days | Baseline, up to Day 29, and through 100 days of follow-up | 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. |
| Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Pre-dose, 2 hours post-dose | — |
| Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Pre-dose, 2 hours post-dose | — |
| Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Baseline, Days 3, 8, 15, 22 and 29 | 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. |
Countries
Australia, Germany, Netherlands, United Kingdom
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Part A: 0.38 mg/kg Single dose administration of ARC-AAT IV injection, 0.38 mg/kg in healthy volunteers | 4 |
| Part A: 1.0 mg/kg Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers | 4 |
| Part A: 2.0 mg/kg Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers | 4 |
| Part A: 3.0 mg/kg Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers | 4 |
| Part A: 4.0 mg/kg Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers | 4 |
| Part A: 5.0 mg/kg Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers | 4 |
| Part A: 6.0 mg/kg Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers | 4 |
| Part A: 7.0 mg/kg Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers | 4 |
| Part A: 8.0 mg/kg Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers | 4 |
| Part A: Placebo Single dose administration of 0.9% normal saline IV injection in healthy volunteers | 18 |
| 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) | 4 |
| Part B: 4.0 mg/kg Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD | 3 |
| Part B: Placebo Single dose administration of 0.9% normal saline IV injection in participants with AATD | 4 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part A: 0.38 mg/kg | Part A: 1.0 mg/kg | Part A: 2.0 mg/kg | Part A: 3.0 mg/kg | Part A: 4.0 mg/kg | Part A: 5.0 mg/kg | Part A: 6.0 mg/kg | Part A: 7.0 mg/kg | Part A: 8.0 mg/kg | Part A: Placebo | Part B: 2.0 mg/kg | Part B: 4.0 mg/kg | Part B: Placebo |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.4 years STANDARD_DEVIATION 14.3 | 39.0 years STANDARD_DEVIATION 9.8 | 25.0 years STANDARD_DEVIATION 4.5 | 30.0 years STANDARD_DEVIATION 7.8 | 29.5 years STANDARD_DEVIATION 10.7 | 32.3 years STANDARD_DEVIATION 5.6 | 23.8 years STANDARD_DEVIATION 4.1 | 32.5 years STANDARD_DEVIATION 15.3 | 26.0 years STANDARD_DEVIATION 5 | 25.0 years STANDARD_DEVIATION 1.8 | 25.4 years STANDARD_DEVIATION 4.8 | 59.0 years STANDARD_DEVIATION 1.8 | 64.3 years STANDARD_DEVIATION 3.8 | 58.8 years STANDARD_DEVIATION 9 |
| Sex: Female, Male Female | 40 Participants | 1 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 3 Participants | 3 Participants | 2 Participants | 12 Participants | 3 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 25 Participants | 3 Participants | 0 Participants | 2 Participants | 3 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 6 Participants | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 18 | 0 / 4 | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 2 / 4 | 2 / 4 | 2 / 4 | 1 / 4 | 3 / 4 | 3 / 4 | 3 / 4 | 1 / 4 | 3 / 4 | 9 / 18 | 3 / 4 | 2 / 3 | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 1 / 18 | 0 / 4 | 0 / 3 | 0 / 4 |
Outcome results
Primary
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values
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.
Time frame: Day 1 through Day 29 ± 1 day
Population: All participants receiving at least 1 dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: 0.38 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Troponin I | 1 participants |
| Part A: 0.38 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Red Cell Distribution Width | 0 participants |
| Part A: 0.38 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | White Cell Count | 0 participants |
| Part A: 0.38 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Monocytes | 0 participants |
| Part A: 0.38 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Neutrophils | 0 participants |
| Part A: 0.38 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Creatine Kinase | 0 participants |
| Part A: 1.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | White Cell Count | 0 participants |
| Part A: 1.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Monocytes | 0 participants |
| Part A: 1.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Red Cell Distribution Width | 0 participants |
| Part A: 1.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Creatine Kinase | 0 participants |
| Part A: 1.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Troponin I | 0 participants |
| Part A: 1.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Neutrophils | 0 participants |
| Part A: 2.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Red Cell Distribution Width | 0 participants |
| Part A: 2.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | White Cell Count | 0 participants |
| Part A: 2.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Neutrophils | 0 participants |
| Part A: 2.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Troponin I | 0 participants |
| Part A: 2.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Creatine Kinase | 0 participants |
| Part A: 2.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Monocytes | 0 participants |
| Part A: 3.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Creatine Kinase | 0 participants |
| Part A: 3.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Neutrophils | 0 participants |
| Part A: 3.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Monocytes | 0 participants |
| Part A: 3.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | White Cell Count | 0 participants |
| Part A: 3.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Troponin I | 0 participants |
| Part A: 3.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Red Cell Distribution Width | 0 participants |
| Part A: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Red Cell Distribution Width | 0 participants |
| Part A: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Troponin I | 0 participants |
| Part A: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | White Cell Count | 0 participants |
| Part A: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Creatine Kinase | 1 participants |
| Part A: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Neutrophils | 1 participants |
| Part A: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Monocytes | 0 participants |
| Part A: 5.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Troponin I | 0 participants |
| Part A: 5.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Neutrophils | 0 participants |
| Part A: 5.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Creatine Kinase | 0 participants |
| Part A: 5.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | White Cell Count | 0 participants |
| Part A: 5.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Monocytes | 0 participants |
| Part A: 5.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Red Cell Distribution Width | 0 participants |
| Part A: 6.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Red Cell Distribution Width | 0 participants |
| Part A: 6.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Troponin I | 0 participants |
| Part A: 6.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Creatine Kinase | 0 participants |
| Part A: 6.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Neutrophils | 0 participants |
| Part A: 6.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Monocytes | 0 participants |
| Part A: 6.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | White Cell Count | 0 participants |
| Part A: 7.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Monocytes | 0 participants |
| Part A: 7.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Troponin I | 0 participants |
| Part A: 7.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Neutrophils | 0 participants |
| Part A: 7.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | White Cell Count | 0 participants |
| Part A: 7.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Creatine Kinase | 0 participants |
| Part A: 7.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Red Cell Distribution Width | 0 participants |
| Part A: 8.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Monocytes | 0 participants |
| Part A: 8.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Neutrophils | 0 participants |
| Part A: 8.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | White Cell Count | 0 participants |
| Part A: 8.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Creatine Kinase | 0 participants |
| Part A: 8.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Red Cell Distribution Width | 0 participants |
| Part A: 8.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Troponin I | 0 participants |
| Part A: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Neutrophils | 0 participants |
| Part A: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Monocytes | 0 participants |
| Part A: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Troponin I | 0 participants |
| Part A: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Creatine Kinase | 0 participants |
| Part A: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | White Cell Count | 0 participants |
| Part A: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Red Cell Distribution Width | 0 participants |
| Part B: 2.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Neutrophils | 1 participants |
| Part B: 2.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Creatine Kinase | 0 participants |
| Part B: 2.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Monocytes | 1 participants |
| Part B: 2.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Red Cell Distribution Width | 1 participants |
| Part B: 2.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | White Cell Count | 1 participants |
| Part B: 2.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Troponin I | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Neutrophils | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Monocytes | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | White Cell Count | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Troponin I | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Creatine Kinase | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Red Cell Distribution Width | 0 participants |
| Part B: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Red Cell Distribution Width | 0 participants |
| Part B: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Neutrophils | 0 participants |
| Part B: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Monocytes | 0 participants |
| Part B: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Troponin I | 0 participants |
| Part B: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | White Cell Count | 0 participants |
| Part B: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values | Creatine Kinase | 0 participants |
Primary
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations
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 \[DLCO\]).
Time frame: Day 1 through Day 29 ± 1 day
Population: All participants receiving at least 1 dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: 0.38 mg/kg | 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 |
| Part A: 0.38 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | ECGs | 0 participants |
| Part A: 0.38 mg/kg | 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 |
| Part A: 0.38 mg/kg | 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 |
| Part A: 0.38 mg/kg | 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 |
| Part A: 1.0 mg/kg | 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 |
| Part A: 1.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | ECGs | 0 participants |
| Part A: 1.0 mg/kg | 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 |
| Part A: 1.0 mg/kg | 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 |
| Part A: 1.0 mg/kg | 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 |
| Part A: 2.0 mg/kg | 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 |
| Part A: 2.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | ECGs | 1 participants |
| Part A: 2.0 mg/kg | 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 |
| Part A: 2.0 mg/kg | 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 |
| Part A: 2.0 mg/kg | 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 |
| Part A: 3.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | ECGs | 0 participants |
| Part A: 3.0 mg/kg | 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 |
| Part A: 3.0 mg/kg | 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 |
| Part A: 3.0 mg/kg | 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 |
| Part A: 3.0 mg/kg | 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 |
| Part A: 4.0 mg/kg | 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 |
| Part A: 4.0 mg/kg | 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 |
| Part A: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | ECGs | 0 participants |
| Part A: 4.0 mg/kg | 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 |
| Part A: 4.0 mg/kg | 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 |
| Part A: 5.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | ECGs | 0 participants |
| Part A: 5.0 mg/kg | 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 |
| Part A: 5.0 mg/kg | 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 |
| Part A: 5.0 mg/kg | 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 |
| Part A: 5.0 mg/kg | 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 |
| Part A: 6.0 mg/kg | 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 |
| Part A: 6.0 mg/kg | 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 |
| Part A: 6.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | ECGs | 0 participants |
| Part A: 6.0 mg/kg | 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 |
| Part A: 6.0 mg/kg | 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 |
| Part A: 7.0 mg/kg | 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 |
| Part A: 7.0 mg/kg | 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 |
| Part A: 7.0 mg/kg | 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 |
| Part A: 7.0 mg/kg | 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 |
| Part A: 7.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | ECGs | 0 participants |
| Part A: 8.0 mg/kg | 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 |
| Part A: 8.0 mg/kg | 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 |
| Part A: 8.0 mg/kg | 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 |
| Part A: 8.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | ECGs | 0 participants |
| Part A: 8.0 mg/kg | 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 |
| Part A: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | ECGs | 0 participants |
| Part A: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | Pulmonary Function | 1 participants |
| Part A: Placebo | 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 |
| Part A: Placebo | 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 |
| Part A: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | Physical Examination Findings | 1 participants |
| Part B: 2.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | ECGs | 0 participants |
| Part B: 2.0 mg/kg | 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 |
| Part B: 2.0 mg/kg | 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 |
| Part B: 2.0 mg/kg | 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 |
| Part B: 2.0 mg/kg | 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 |
| Part B: 4.0 mg/kg | 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 |
| Part B: 4.0 mg/kg | 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 |
| Part B: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | ECGs | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | Physical Examination Findings | 1 participants |
| Part B: 4.0 mg/kg | 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 |
| Part B: Placebo | 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 |
| Part B: Placebo | 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 |
| Part B: Placebo | 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 |
| Part B: Placebo | Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations | ECGs | 0 participants |
| Part B: Placebo | 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 |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs
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.
Time frame: From the first dose of study treatment through Day 29 ± 1 day
Population: All participants receiving at least 1 dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: 0.38 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Severe TEAEs | 0 participants |
| Part A: 0.38 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | TEAEs | 2 participants |
| Part A: 0.38 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related TEAEs | 1 participants |
| Part A: 0.38 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Discontinuations Due to TEAEs | 0 participants |
| Part A: 0.38 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | SAEs | 0 participants |
| Part A: 0.38 mg/kg | 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 |
| Part A: 0.38 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Mild or Moderate TEAEs | 2 participants |
| Part A: 0.38 mg/kg | 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 |
| Part A: 1.0 mg/kg | 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 |
| Part A: 1.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Discontinuations Due to TEAEs | 0 participants |
| Part A: 1.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related Moderate TEAEs | 0 participants |
| Part A: 1.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | TEAEs | 2 participants |
| Part A: 1.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Severe TEAEs | 0 participants |
| Part A: 1.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Mild or Moderate TEAEs | 2 participants |
| Part A: 1.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related TEAEs | 1 participants |
| Part A: 1.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | SAEs | 0 participants |
| Part A: 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Mild or Moderate TEAEs | 2 participants |
| Part A: 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | SAEs | 0 participants |
| Part A: 2.0 mg/kg | 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 |
| Part A: 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Severe TEAEs | 0 participants |
| Part A: 2.0 mg/kg | 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 |
| Part A: 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | TEAEs | 2 participants |
| Part A: 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related TEAEs | 2 participants |
| Part A: 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Discontinuations Due to TEAEs | 0 participants |
| Part A: 3.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | SAEs | 0 participants |
| Part A: 3.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Severe TEAEs | 0 participants |
| Part A: 3.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Mild or Moderate TEAEs | 1 participants |
| Part A: 3.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Discontinuations Due to TEAEs | 0 participants |
| Part A: 3.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related TEAEs | 1 participants |
| Part A: 3.0 mg/kg | 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 |
| Part A: 3.0 mg/kg | 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 |
| Part A: 3.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | TEAEs | 1 participants |
| Part A: 4.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Discontinuations Due to TEAEs | 0 participants |
| Part A: 4.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | TEAEs | 3 participants |
| Part A: 4.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related Moderate TEAEs | 0 participants |
| Part A: 4.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related TEAEs | 1 participants |
| Part A: 4.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | SAEs | 0 participants |
| Part A: 4.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Mild or Moderate TEAEs | 3 participants |
| Part A: 4.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Severe TEAEs | 0 participants |
| Part A: 4.0 mg/kg | 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 |
| Part A: 5.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Severe TEAEs | 0 participants |
| Part A: 5.0 mg/kg | 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 |
| Part A: 5.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Discontinuations Due to TEAEs | 0 participants |
| Part A: 5.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related Moderate TEAEs | 0 participants |
| Part A: 5.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | SAEs | 0 participants |
| Part A: 5.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related TEAEs | 2 participants |
| Part A: 5.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | TEAEs | 3 participants |
| Part A: 5.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Mild or Moderate TEAEs | 3 participants |
| Part A: 6.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related Moderate TEAEs | 0 participants |
| Part A: 6.0 mg/kg | 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 |
| Part A: 6.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Mild or Moderate TEAEs | 3 participants |
| Part A: 6.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | SAEs | 0 participants |
| Part A: 6.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Discontinuations Due to TEAEs | 0 participants |
| Part A: 6.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | TEAEs | 3 participants |
| Part A: 6.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related TEAEs | 0 participants |
| Part A: 6.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Severe TEAEs | 0 participants |
| Part A: 7.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Severe TEAEs | 0 participants |
| Part A: 7.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related TEAEs | 0 participants |
| Part A: 7.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | SAEs | 0 participants |
| Part A: 7.0 mg/kg | 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 |
| Part A: 7.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related Moderate TEAEs | 0 participants |
| Part A: 7.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | TEAEs | 1 participants |
| Part A: 7.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Discontinuations Due to TEAEs | 0 participants |
| Part A: 7.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Mild or Moderate TEAEs | 1 participants |
| Part A: 8.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Severe TEAEs | 0 participants |
| Part A: 8.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related TEAEs | 3 participants |
| Part A: 8.0 mg/kg | 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 |
| Part A: 8.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | SAEs | 0 participants |
| Part A: 8.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Discontinuations Due to TEAEs | 0 participants |
| Part A: 8.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Mild or Moderate TEAEs | 3 participants |
| Part A: 8.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | TEAEs | 3 participants |
| Part A: 8.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related Moderate TEAEs | 3 participants |
| Part A: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related TEAEs | 1 participants |
| Part A: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related Moderate TEAEs | 0 participants |
| Part A: Placebo | 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 |
| Part A: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Discontinuations Due to TEAEs | 0 participants |
| Part A: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Mild or Moderate TEAEs | 8 participants |
| Part A: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Severe TEAEs | 1 participants |
| Part A: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | TEAEs | 9 participants |
| Part A: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | SAEs | 1 participants |
| Part B: 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Discontinuations Due to TEAEs | 0 participants |
| Part B: 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related TEAEs | 1 participants |
| Part B: 2.0 mg/kg | 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 |
| Part B: 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Severe TEAEs | 0 participants |
| Part B: 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Mild or Moderate TEAEs | 3 participants |
| Part B: 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | TEAEs | 3 participants |
| Part B: 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | SAEs | 0 participants |
| Part B: 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related Moderate TEAEs | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Mild or Moderate TEAEs | 2 participants |
| Part B: 4.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Severe TEAEs | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related TEAEs | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Discontinuations Due to TEAEs | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | TEAEs | 2 participants |
| Part B: 4.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related Moderate TEAEs | 0 participants |
| Part B: 4.0 mg/kg | 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 |
| Part B: 4.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | SAEs | 0 participants |
| Part B: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | SAEs | 0 participants |
| Part B: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | TEAEs | 4 participants |
| Part B: Placebo | 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 |
| Part B: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related TEAEs | 0 participants |
| Part B: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Discontinuations Due to TEAEs | 0 participants |
| Part B: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Mild or Moderate TEAEs | 4 participants |
| Part B: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Study Drug Related Moderate TEAEs | 0 participants |
| Part B: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs | Severe TEAEs | 0 participants |
Primary
Percentage Reduction From Baseline of AAT Up to Day 29
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: 0.38 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 8 | 0.93 percentage reduction | Standard Deviation 2.86 |
| Part A: 0.38 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 15 | 5.00 percentage reduction | Standard Deviation 2.62 |
| Part A: 0.38 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 22 | 1.42 percentage reduction | Standard Deviation 4.01 |
| Part A: 0.38 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 3 | -4.70 percentage reduction | Standard Deviation 8.45 |
| Part A: 0.38 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 29 | 0.19 percentage reduction | Standard Deviation 10.37 |
| Part A: 1.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 29 | 25.87 percentage reduction | Standard Deviation 6.58 |
| Part A: 1.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 3 | -7.00 percentage reduction | Standard Deviation 3.19 |
| Part A: 1.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 22 | 6.81 percentage reduction | Standard Deviation 8.81 |
| Part A: 1.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 8 | 10.90 percentage reduction | Standard Deviation 8.3 |
| Part A: 1.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 15 | 3.89 percentage reduction | Standard Deviation 2.78 |
| Part A: 2.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 8 | 13.40 percentage reduction | Standard Deviation 11.68 |
| Part A: 2.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 29 | 13.93 percentage reduction | Standard Deviation 17.16 |
| Part A: 2.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 15 | 26.72 percentage reduction | Standard Deviation 14.31 |
| Part A: 2.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 22 | 15.59 percentage reduction | Standard Deviation 9.21 |
| Part A: 2.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 3 | -1.94 percentage reduction | Standard Deviation 4.49 |
| Part A: 3.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 29 | 27.40 percentage reduction | Standard Deviation 10.65 |
| Part A: 3.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 3 | 13.76 percentage reduction | Standard Deviation 4.74 |
| Part A: 3.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 15 | 33.65 percentage reduction | Standard Deviation 14.66 |
| Part A: 3.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 8 | 33.20 percentage reduction | Standard Deviation 14.33 |
| Part A: 3.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 22 | 35.50 percentage reduction | Standard Deviation 15.24 |
| Part A: 4.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 22 | 58.64 percentage reduction | Standard Deviation 13.55 |
| Part A: 4.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 29 | 50.02 percentage reduction | Standard Deviation 20.46 |
| Part A: 4.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 15 | 61.53 percentage reduction | Standard Deviation 11.75 |
| Part A: 4.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 3 | 20.76 percentage reduction | Standard Deviation 5.86 |
| Part A: 4.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 8 | 46.92 percentage reduction | Standard Deviation 6.16 |
| Part A: 5.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 22 | 77.18 percentage reduction | Standard Deviation 9.94 |
| Part A: 5.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 3 | 21.65 percentage reduction | Standard Deviation 5.28 |
| Part A: 5.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 29 | 73.15 percentage reduction | Standard Deviation 14.46 |
| Part A: 5.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 8 | 58.52 percentage reduction | Standard Deviation 6.15 |
| Part A: 5.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 15 | 74.20 percentage reduction | Standard Deviation 7.03 |
| Part A: 6.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 29 | 82.99 percentage reduction | Standard Deviation 4.19 |
| Part A: 6.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 22 | 83.12 percentage reduction | Standard Deviation 3.67 |
| Part A: 6.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 3 | 22.20 percentage reduction | Standard Deviation 8.8 |
| Part A: 6.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 15 | 75.75 percentage reduction | Standard Deviation 5.95 |
| Part A: 6.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 8 | 58.44 percentage reduction | Standard Deviation 7.5 |
| Part A: 7.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 8 | 50.95 percentage reduction | Standard Deviation 6.82 |
| Part A: 7.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 29 | 78.20 percentage reduction | Standard Deviation 7.83 |
| Part A: 7.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 15 | 73.57 percentage reduction | Standard Deviation 2.76 |
| Part A: 7.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 3 | 20.35 percentage reduction | Standard Deviation 11.83 |
| Part A: 7.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 22 | 81.14 percentage reduction | Standard Deviation 1.17 |
| Part A: 8.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 22 | 87.47 percentage reduction | Standard Deviation 2.09 |
| Part A: 8.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 29 | 87.93 percentage reduction | Standard Deviation 1.75 |
| Part A: 8.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 3 | 30.07 percentage reduction | Standard Deviation 6.37 |
| Part A: 8.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 8 | 58.66 percentage reduction | Standard Deviation 2.99 |
| Part A: 8.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 15 | 79.18 percentage reduction | Standard Deviation 4.03 |
| Part A: Placebo | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 29 | -1.56 percentage reduction | Standard Deviation 8.66 |
| Part A: Placebo | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 15 | 0.78 percentage reduction | Standard Deviation 11.91 |
| Part A: Placebo | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 8 | -0.26 percentage reduction | Standard Deviation 10.8 |
| Part A: Placebo | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 3 | -4.65 percentage reduction | Standard Deviation 11.13 |
| Part A: Placebo | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 22 | 0.50 percentage reduction | Standard Deviation 13.48 |
| Part B: 2.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 3 | 11.5 percentage reduction | Standard Deviation 11.5 |
| Part B: 2.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 29 | 21.0 percentage reduction | Standard Deviation 24.4 |
| Part B: 2.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 22 | 25.1 percentage reduction | Standard Deviation 17.2 |
| Part B: 2.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 15 | 37.5 percentage reduction | Standard Deviation 20.4 |
| Part B: 2.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 8 | 43.1 percentage reduction | Standard Deviation 26.7 |
| Part B: 4.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 29 | 65.2 percentage reduction | Standard Deviation 8.7 |
| Part B: 4.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 15 | 77.7 percentage reduction | Standard Deviation 1.5 |
| Part B: 4.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 22 | 59.5 percentage reduction | Standard Deviation 13.4 |
| Part B: 4.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 3 | 43.8 percentage reduction | Standard Deviation 5.6 |
| Part B: 4.0 mg/kg | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 8 | 54.4 percentage reduction | Standard Deviation 22.2 |
| Part B: Placebo | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 29 | -7.2 percentage reduction | Standard Deviation 30.3 |
| Part B: Placebo | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 22 | 1.7 percentage reduction | Standard Deviation 20.8 |
| Part B: Placebo | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 8 | 7.0 percentage reduction | Standard Deviation 36.9 |
| Part B: Placebo | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 3 | -13.0 percentage reduction | Standard Deviation 31.9 |
| Part B: Placebo | Percentage Reduction From Baseline of AAT Up to Day 29 | Day 15 | 7.2 percentage reduction | Standard Deviation 19.8 |
Primary
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)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: 0.38 mg/kg | 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 |
| Part A: 0.38 mg/kg | 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 |
| Part A: 1.0 mg/kg | 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 | 85906 hr*ng/mL | Standard Deviation 12529 |
| Part A: 1.0 mg/kg | 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 | 103116 hr*ng/mL | Standard Deviation 48837 |
| Part A: 2.0 mg/kg | 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 | 164856 hr*ng/mL | Standard Deviation 58070 |
| Part A: 2.0 mg/kg | 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 | 277684 hr*ng/mL | Standard Deviation 119873 |
| Part A: 3.0 mg/kg | 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 | 285487 hr*ng/mL | Standard Deviation 62310 |
| Part A: 3.0 mg/kg | 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 | 380506 hr*ng/mL | Standard Deviation 89117 |
| Part A: 4.0 mg/kg | 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 | 441239 hr*ng/mL | Standard Deviation 39032 |
| Part A: 4.0 mg/kg | 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 | 559372 hr*ng/mL | Standard Deviation 82769 |
| Part A: 5.0 mg/kg | 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 | 569056 hr*ng/mL | Standard Deviation 129569 |
| Part A: 5.0 mg/kg | 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 | 547045 hr*ng/mL | Standard Deviation 52126 |
| Part A: 6.0 mg/kg | 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 | 872798 hr*ng/mL | Standard Deviation 136277 |
| Part A: 6.0 mg/kg | 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 | 719843 hr*ng/mL | Standard Deviation 226599 |
| Part A: 7.0 mg/kg | 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 | 771924 hr*ng/mL | Standard Deviation 100469 |
| Part A: 7.0 mg/kg | 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 | 952668 hr*ng/mL | Standard Deviation 99324 |
| Part A: 8.0 mg/kg | 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 | 916343 hr*ng/mL | Standard Deviation 147924 |
| Part A: 8.0 mg/kg | 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 | 1251318 hr*ng/mL | Standard Deviation 138571 |
Comparison: Dose-Proportionality of Pharmacokinetic Parameter AUCinf for Analyte AD00370
Comparison: Dose-Proportionality of Pharmacokinetic Parameter AUCinf for Analyte AD0037095% CI: [1.11, 1.249]
Comparison: Dose-Proportionality of Pharmacokinetic Parameter AUCinf for Analyte ARC-MLP
Comparison: Dose-Proportionality of Pharmacokinetic Parameter AUCinf for Analyte ARC-MLP95% CI: [1.081, 1.245]
Primary
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)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: 0.38 mg/kg | 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 |
| Part A: 0.38 mg/kg | 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 |
| Part A: 1.0 mg/kg | 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 | 85138 hr*ng/mL | Standard Deviation 12234 |
| Part A: 1.0 mg/kg | 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 | 82627 hr*ng/mL | Standard Deviation 32332 |
| Part A: 2.0 mg/kg | 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 | 162198 hr*ng/mL | Standard Deviation 56129 |
| Part A: 2.0 mg/kg | 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 | 213250 hr*ng/mL | Standard Deviation 67886 |
| Part A: 3.0 mg/kg | 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 | 282710 hr*ng/mL | Standard Deviation 61810 |
| Part A: 3.0 mg/kg | 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 | 291876 hr*ng/mL | Standard Deviation 58240 |
| Part A: 4.0 mg/kg | 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 | 438532 hr*ng/mL | Standard Deviation 38111 |
| Part A: 4.0 mg/kg | 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 | 458790 hr*ng/mL | Standard Deviation 48790 |
| Part A: 5.0 mg/kg | 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 | 459939 hr*ng/mL | Standard Deviation 81820 |
| Part A: 5.0 mg/kg | 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 | 541628 hr*ng/mL | Standard Deviation 49787 |
| Part A: 6.0 mg/kg | 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 | 699833 hr*ng/mL | Standard Deviation 85172 |
| Part A: 6.0 mg/kg | 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 | 708648 hr*ng/mL | Standard Deviation 212442 |
| Part A: 7.0 mg/kg | 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 | 763392 hr*ng/mL | Standard Deviation 96095 |
| Part A: 7.0 mg/kg | 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 | 716938 hr*ng/mL | Standard Deviation 46783 |
| Part A: 8.0 mg/kg | 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 | 908117 hr*ng/mL | Standard Deviation 144892 |
| Part A: 8.0 mg/kg | 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 | 1011569 hr*ng/mL | Standard Deviation 101693 |
Comparison: Dose-Proportionality of Pharmacokinetic Parameter AUC0-24 for Analyte AD00370
Comparison: Dose-Proportionality of Pharmacokinetic Parameter AUC0-24 for Analyte AD0037095% CI: [1.112, 1.249]
Comparison: Dose-Proportionality of Pharmacokinetic Parameter AUC0-24 for Analyte ARC-MLP
Comparison: Dose-Proportionality of Pharmacokinetic Parameter AUC0-24 for Analyte ARC-MLP95% CI: [1.08, 1.215]
Primary
Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: 0.38 mg/kg | 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 |
| Part A: 0.38 mg/kg | 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 1.5 |
| Part A: 1.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 3.91 hours | Standard Deviation 0.09 |
| Part A: 1.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte ARC-MLP | 8.60 hours | Standard Deviation 2.88 |
| Part A: 2.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 4.09 hours | Standard Deviation 0.31 |
| Part A: 2.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte ARC-MLP | 9.77 hours | Standard Deviation 3.39 |
| Part A: 3.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 3.99 hours | Standard Deviation 0.09 |
| Part A: 3.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte ARC-MLP | 9.83 hours | Standard Deviation 3.46 |
| Part A: 4.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 3.75 hours | Standard Deviation 0.22 |
| Part A: 4.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte ARC-MLP | 8.43 hours | Standard Deviation 1.68 |
| Part A: 5.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte ARC-MLP | 8.93 hours | Standard Deviation 1.98 |
| Part A: 5.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 3.78 hours | Standard Deviation 0.12 |
| Part A: 6.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte ARC-MLP | 9.17 hours | Standard Deviation 1.4 |
| Part A: 6.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 3.80 hours | Standard Deviation 0.53 |
| Part A: 7.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 3.90 hours | Standard Deviation 0.23 |
| Part A: 7.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte ARC-MLP | 11.3 hours | Standard Deviation 1.5 |
| Part A: 8.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 3.83 hours | Standard Deviation 0.19 |
| Part A: 8.0 mg/kg | Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte ARC-MLP | 9.52 hours | Standard Deviation 0.61 |
Primary
Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: 0.38 mg/kg | 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 |
| Part A: 0.38 mg/kg | 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 |
| Part A: 1.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte AD00370 | 15500 ng/mL | Standard Deviation 2811 |
| Part A: 1.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte ARC-MLP | 9350 ng/mL | Standard Deviation 2368 |
| Part A: 2.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte AD00370 | 32400 ng/mL | Standard Deviation 7005 |
| Part A: 2.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte ARC-MLP | 20700 ng/mL | Standard Deviation 3334 |
| Part A: 3.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte AD00370 | 50650 ng/mL | Standard Deviation 7461 |
| Part A: 3.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte ARC-MLP | 27050 ng/mL | Standard Deviation 5390 |
| Part A: 4.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte AD00370 | 75625 ng/mL | Standard Deviation 8152 |
| Part A: 4.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte ARC-MLP | 43425 ng/mL | Standard Deviation 3872 |
| Part A: 5.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte ARC-MLP | 48975 ng/mL | Standard Deviation 5590 |
| Part A: 5.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte AD00370 | 93275 ng/mL | Standard Deviation 6133 |
| Part A: 6.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte ARC-MLP | 70050 ng/mL | Standard Deviation 6946 |
| Part A: 6.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte AD00370 | 115750 ng/mL | Standard Deviation 11871 |
| Part A: 7.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte AD00370 | 130250 ng/mL | Standard Deviation 14127 |
| Part A: 7.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte ARC-MLP | 62525 ng/mL | Standard Deviation 4029 |
| Part A: 8.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte AD00370 | 167000 ng/mL | Standard Deviation 7810 |
| Part A: 8.0 mg/kg | Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A) | Analyte ARC-MLP | 84733 ng/mL | Standard Deviation 2875 |
Comparison: Dose-Proportionality of Pharmacokinetic Parameter Cmax for Analyte AD00370
Comparison: Dose-Proportionality of Pharmacokinetic Parameter Cmax for Analyte AD0037095% CI: [1.128, 1.218]
Comparison: Dose-Proportionality of Pharmacokinetic Parameter Cmax for Analyte ARC-MLP
Comparison: Dose-Proportionality of Pharmacokinetic Parameter Cmax for Analyte ARC-MLP95% CI: [1.054, 1.153]
Primary
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)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: 0.38 mg/kg | 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 |
| Part A: 0.38 mg/kg | 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 0.05 |
| Part A: 1.0 mg/kg | 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 | 0.0879 1/hour | Standard Deviation 0.0297 |
| Part A: 1.0 mg/kg | 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 | 0.177 1/hour | Standard Deviation 0.004 |
| Part A: 2.0 mg/kg | 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 | 0.170 1/hour | Standard Deviation 0.013 |
| Part A: 2.0 mg/kg | 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 | 0.0778 1/hour | Standard Deviation 0.0265 |
| Part A: 3.0 mg/kg | 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 | 0.0762 1/hour | Standard Deviation 0.0218 |
| Part A: 3.0 mg/kg | 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 | 0.174 1/hour | Standard Deviation 0.004 |
| Part A: 4.0 mg/kg | 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 | 0.0846 1/hour | Standard Deviation 0.0158 |
| Part A: 4.0 mg/kg | 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 | 0.185 1/hour | Standard Deviation 0.011 |
| Part A: 5.0 mg/kg | 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 | 0.0815 1/hour | Standard Deviation 0.0231 |
| Part A: 5.0 mg/kg | 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 | 0.183 1/hour | Standard Deviation 0.006 |
| Part A: 6.0 mg/kg | 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 | 0.185 1/hour | Standard Deviation 0.023 |
| Part A: 6.0 mg/kg | 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 | 0.0768 1/hour | Standard Deviation 0.0104 |
| Part A: 7.0 mg/kg | 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 | 0.178 1/hour | Standard Deviation 0.01 |
| Part A: 7.0 mg/kg | 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 | 0.0622 1/hour | Standard Deviation 0.0077 |
| Part A: 8.0 mg/kg | 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 | 0.0730 1/hour | Standard Deviation 0.0046 |
| Part A: 8.0 mg/kg | 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 | 0.181 1/hour | Standard Deviation 0.009 |
Primary
Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A)
Time frame: 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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: 0.38 mg/kg | 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 |
| Part A: 0.38 mg/kg | Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 0.083 hour |
| Part A: 1.0 mg/kg | 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 |
| Part A: 1.0 mg/kg | Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 0.083 hour |
| Part A: 2.0 mg/kg | Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 0.083 hour |
| Part A: 2.0 mg/kg | 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 |
| Part A: 3.0 mg/kg | 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 |
| Part A: 3.0 mg/kg | Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 0.083 hour |
| Part A: 4.0 mg/kg | Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 0.083 hour |
| Part A: 4.0 mg/kg | 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 |
| Part A: 5.0 mg/kg | 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 |
| Part A: 5.0 mg/kg | Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 0.083 hour |
| Part A: 6.0 mg/kg | Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 0.083 hour |
| Part A: 6.0 mg/kg | 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 |
| Part A: 7.0 mg/kg | Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 0.083 hour |
| Part A: 7.0 mg/kg | Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte ARC-MLP | 0.50 hour |
| Part A: 8.0 mg/kg | Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte AD00370 | 0.50 hour |
| Part A: 8.0 mg/kg | Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A) | Analyte ARC-MLP | 0.50 hour |
Secondary
Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT)
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: 0.38 mg/kg | Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT) | 5.0 percentage reduction |
| Part A: 1.0 mg/kg | Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT) | 25.9 percentage reduction |
| Part A: 2.0 mg/kg | Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT) | 26.7 percentage reduction |
| Part A: 3.0 mg/kg | Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT) | 35.5 percentage reduction |
| Part A: 4.0 mg/kg | Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT) | 61.5 percentage reduction |
| Part A: 5.0 mg/kg | Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT) | 77.2 percentage reduction |
| Part A: 6.0 mg/kg | Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT) | 83.1 percentage reduction |
| Part A: 7.0 mg/kg | Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT) | 81.1 percentage reduction |
| Part A: 8.0 mg/kg | Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT) | 87.9 percentage reduction |
| Part A: Placebo | Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT) | 0.78 percentage reduction |
| Part B: 2.0 mg/kg | Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT) | 43.1 percentage reduction |
| Part B: 4.0 mg/kg | Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT) | 77.7 percentage reduction |
| Part B: Placebo | Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT) | 7.2 percentage reduction |
Secondary
Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose
Time frame: Pre-dose, 2 hours post-dose
Population: Participants with available data for given parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: 0.38 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C4a | -5 percentage change | Standard Deviation 7 |
| Part A: 0.38 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum CH50 | -5 percentage change | Standard Deviation 8 |
| Part A: 0.38 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C5a | 2 percentage change | Standard Deviation 7 |
| Part A: 0.38 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Plasma Bb | 18 percentage change | Standard Deviation 16 |
| Part A: 0.38 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C3a | -12 percentage change | Standard Deviation 6 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C3a | 30 percentage change | Standard Deviation 42 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C4a | 37 percentage change | Standard Deviation 70 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Plasma Bb | 56 percentage change | Standard Deviation 25 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C5a | 2 percentage change | Standard Deviation 7 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum CH50 | -14 percentage change | Standard Deviation 11 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum CH50 | -14 percentage change | Standard Deviation 7 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C3a | -22 percentage change | Standard Deviation 24 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C5a | -16 percentage change | Standard Deviation 5 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C4a | -11 percentage change | Standard Deviation 10 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Plasma Bb | 76 percentage change | Standard Deviation 37 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C4a | 2 percentage change | Standard Deviation 8 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Plasma Bb | 133 percentage change | Standard Deviation 29 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum CH50 | -8 percentage change | Standard Deviation 8 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C3a | -0 percentage change | Standard Deviation 8 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C5a | -2 percentage change | Standard Deviation 25 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C5a | -14 percentage change | Standard Deviation 7 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C4a | 16 percentage change | Standard Deviation 13 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Plasma Bb | 181 percentage change | Standard Deviation 185 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C3a | 71 percentage change | Standard Deviation 156 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum CH50 | -16 percentage change | Standard Deviation 4 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C3a | -5 percentage change | Standard Deviation 18 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum CH50 | -17 percentage change | Standard Deviation 8 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Plasma Bb | 137 percentage change | Standard Deviation 85 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C4a | -8 percentage change | Standard Deviation 27 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C5a | 2 percentage change | Standard Deviation 15 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C4a | 78 percentage change | Standard Deviation 107 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Plasma Bb | 70 percentage change | Standard Deviation 63 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C3a | 14 percentage change | Standard Deviation 56 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C5a | 0 percentage change | Standard Deviation 8 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum CH50 | -10 percentage change | Standard Deviation 4 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C3a | 40 percentage change | Standard Deviation 50 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C5a | 6 percentage change | Standard Deviation 6 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C4a | 60 percentage change | Standard Deviation 53 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum CH50 | -13 percentage change | Standard Deviation 13 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Plasma Bb | 147 percentage change | Standard Deviation 73 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C5a | 6 percentage change | Standard Deviation 12 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Plasma Bb | 309 percentage change | Standard Deviation 174 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C4a | -1 percentage change | Standard Deviation 15 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum CH50 | -19 percentage change | Standard Deviation 10 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C3a | 34 percentage change | Standard Deviation 30 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C4a | -19 percentage change | Standard Deviation 35 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C3a | -11 percentage change | Standard Deviation 23 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C5a | -2 percentage change | Standard Deviation 18 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Plasma Bb | -7 percentage change | Standard Deviation 9 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum CH50 | -3 percentage change | Standard Deviation 9 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum CH50 | -3 percentage change | Standard Deviation 3 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C3a | -18 percentage change | Standard Deviation 23 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C5a | -4 percentage change | Standard Deviation 16 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C4a | -35 percentage change | Standard Deviation 21 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Plasma Bb | 56 percentage change | Standard Deviation 61 |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C3a | 219 percentage change | — |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Plasma Bb | 59 percentage change | — |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C4a | 160 percentage change | — |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C5a | 22 percentage change | — |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum CH50 | -18 percentage change | — |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C4a | -15 percentage change | Standard Deviation 42 |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum CH50 | -0 percentage change | Standard Deviation 13 |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C5a | -4 percentage change | Standard Deviation 10 |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Plasma Bb | -14 percentage change | Standard Deviation 7 |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose | Serum C3a | 16 percentage change | Standard Deviation 40 |
Secondary
Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose
Time frame: Pre-dose, 2 hours post-dose
Population: Participants with available data for given parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: 0.38 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interferon alpha 2 | 0 percentage change | Standard Deviation 0 |
| Part A: 0.38 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p70 | 0 percentage change | Standard Deviation 0 |
| Part A: 0.38 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-10 | -5 percentage change | Standard Deviation 19 |
| Part A: 0.38 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p40 | 2 percentage change | Standard Deviation 37 |
| Part A: 0.38 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-8 | 32 percentage change | Standard Deviation 70 |
| Part A: 0.38 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum tumor necrosis factor alpha | 66 percentage change | Standard Deviation 69 |
| Part A: 0.38 mg/kg | 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 |
| Part A: 0.38 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-6 | 5 percentage change | Standard Deviation 8 |
| Part A: 0.38 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-1 beta | 0 percentage change | Standard Deviation 0 |
| Part A: 0.38 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum monocyte chemoattractant protein-1 | 123 percentage change | Standard Deviation 171 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-1 beta | 0 percentage change | Standard Deviation 0 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p70 | 0 percentage change | Standard Deviation 0 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum macrophage inflammatory protein-1 alpha | 294 percentage change | Standard Deviation 275 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum monocyte chemoattractant protein-1 | 442 percentage change | Standard Deviation 133 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p40 | 2 percentage change | Standard Deviation 5 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interferon alpha 2 | 0 percentage change | Standard Deviation 0 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-6 | 79 percentage change | Standard Deviation 141 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-8 | 280 percentage change | Standard Deviation 328 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum tumor necrosis factor alpha | 207 percentage change | Standard Deviation 90 |
| Part A: 1.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-10 | 72 percentage change | Standard Deviation 134 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-1 beta | 0 percentage change | Standard Deviation 0 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interferon alpha 2 | 0 percentage change | Standard Deviation 0 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum tumor necrosis factor alpha | 286 percentage change | Standard Deviation 90 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum macrophage inflammatory protein-1 alpha | 386 percentage change | Standard Deviation 556 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-6 | 95 percentage change | Standard Deviation 113 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum monocyte chemoattractant protein-1 | 505 percentage change | Standard Deviation 254 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p70 | 0 percentage change | Standard Deviation 0 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p40 | 5 percentage change | Standard Deviation 8 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-8 | 336 percentage change | Standard Deviation 297 |
| Part A: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-10 | 51 percentage change | Standard Deviation 52 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-6 | 50 percentage change | Standard Deviation 64 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-1 beta | 0 percentage change | Standard Deviation 0 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-8 | 103 percentage change | Standard Deviation 101 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-10 | 42 percentage change | Standard Deviation 45 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p40 | 6 percentage change | Standard Deviation 9 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p70 | 0 percentage change | Standard Deviation 0 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum monocyte chemoattractant protein-1 | 632 percentage change | Standard Deviation 281 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum macrophage inflammatory protein-1 alpha | 264 percentage change | Standard Deviation 438 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum tumor necrosis factor alpha | 187 percentage change | Standard Deviation 156 |
| Part A: 3.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interferon alpha 2 | 0 percentage change | Standard Deviation 0 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-1 beta | 0 percentage change | Standard Deviation 0 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-6 | 277 percentage change | Standard Deviation 308 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-10 | 27 percentage change | Standard Deviation 54 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p40 | 0 percentage change | Standard Deviation 0 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p70 | 54 percentage change | Standard Deviation 108 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum macrophage inflammatory protein-1 alpha | 1674 percentage change | Standard Deviation 1022 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-8 | 1712 percentage change | Standard Deviation 981 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum tumor necrosis factor alpha | 818 percentage change | Standard Deviation 344 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum monocyte chemoattractant protein-1 | 1176 percentage change | Standard Deviation 427 |
| Part A: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interferon alpha 2 | 0 percentage change | Standard Deviation 0 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p70 | 0 percentage change | Standard Deviation 0 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-6 | 100 percentage change | Standard Deviation 191 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interferon alpha 2 | 4 percentage change | Standard Deviation 7 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-1 beta | 0 percentage change | Standard Deviation 0 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum tumor necrosis factor alpha | 476 percentage change | Standard Deviation 137 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p40 | 0 percentage change | Standard Deviation 0 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum macrophage inflammatory protein-1 alpha | 1096 percentage change | Standard Deviation 578 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-8 | 564 percentage change | Standard Deviation 576 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum monocyte chemoattractant protein-1 | 1297 percentage change | Standard Deviation 747 |
| Part A: 5.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-10 | 19 percentage change | Standard Deviation 28 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-8 | 252 percentage change | Standard Deviation 363 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum macrophage inflammatory protein-1 alpha | 406 percentage change | Standard Deviation 416 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-10 | 116 percentage change | Standard Deviation 160 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-6 | 146 percentage change | Standard Deviation 261 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p70 | 0 percentage change | Standard Deviation 0 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interferon alpha 2 | 73 percentage change | Standard Deviation 147 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum tumor necrosis factor alpha | 301 percentage change | Standard Deviation 237 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum monocyte chemoattractant protein-1 | 543 percentage change | Standard Deviation 497 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p40 | 152 percentage change | Standard Deviation 217 |
| Part A: 6.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-1 beta | 0 percentage change | Standard Deviation 0 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum monocyte chemoattractant protein-1 | 906 percentage change | Standard Deviation 720 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-10 | 377 percentage change | Standard Deviation 498 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interferon alpha 2 | 172 percentage change | Standard Deviation 366 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p40 | -9 percentage change | Standard Deviation 19 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-6 | 258 percentage change | Standard Deviation 285 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p70 | 166 percentage change | Standard Deviation 389 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum macrophage inflammatory protein-1 alpha | 1003 percentage change | Standard Deviation 814 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-1 beta | -9 percentage change | Standard Deviation 17 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum tumor necrosis factor alpha | 761 percentage change | Standard Deviation 492 |
| Part A: 7.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-8 | 695 percentage change | Standard Deviation 635 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p70 | 82 percentage change | Standard Deviation 130 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interferon alpha 2 | 515 percentage change | Standard Deviation 529 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-6 | 364 percentage change | Standard Deviation 255 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum monocyte chemoattractant protein-1 | 2014 percentage change | Standard Deviation 427 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum macrophage inflammatory protein-1 alpha | 854 percentage change | Standard Deviation 538 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-1 beta | 9 percentage change | Standard Deviation 18 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p40 | 29 percentage change | Standard Deviation 38 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum tumor necrosis factor alpha | 742 percentage change | Standard Deviation 273 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-10 | 638 percentage change | Standard Deviation 536 |
| Part A: 8.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-8 | 2015 percentage change | Standard Deviation 1569 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p40 | -3 percentage change | Standard Deviation 10 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-6 | -1 percentage change | Standard Deviation 7 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum tumor necrosis factor alpha | 3 percentage change | Standard Deviation 27 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-10 | -2 percentage change | Standard Deviation 7 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interferon alpha 2 | 5 percentage change | Standard Deviation 20 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p70 | -1 percentage change | Standard Deviation 4 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum macrophage inflammatory protein-1 alpha | 15 percentage change | Standard Deviation 69 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum monocyte chemoattractant protein-1 | 1 percentage change | Standard Deviation 13 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-1 beta | 0 percentage change | Standard Deviation 0 |
| Part A: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-8 | -6 percentage change | Standard Deviation 17 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interferon alpha 2 | -3 percentage change | Standard Deviation 7 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p70 | -3 percentage change | Standard Deviation 5 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum macrophage inflammatory protein-1 alpha | 246 percentage change | Standard Deviation 304 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-1 beta | -2 percentage change | Standard Deviation 10 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum tumor necrosis factor alpha | 107 percentage change | Standard Deviation 152 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-8 | 197 percentage change | Standard Deviation 319 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum monocyte chemoattractant protein-1 | 262 percentage change | Standard Deviation 262 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-10 | 0 percentage change | Standard Deviation 0 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p40 | -4 percentage change | Standard Deviation 13 |
| Part B: 2.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-6 | 60 percentage change | Standard Deviation 52 |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum monocyte chemoattractant protein-1 | 44 percentage change | — |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-1 beta | 114 percentage change | — |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p40 | 79 percentage change | — |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum macrophage inflammatory protein-1 alpha | 0 percentage change | — |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-8 | 46 percentage change | — |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interferon alpha 2 | 700 percentage change | — |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p70 | 48 percentage change | — |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-6 | 130 percentage change | — |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum tumor necrosis factor alpha | 55 percentage change | — |
| Part B: 4.0 mg/kg | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-10 | 0 percentage change | — |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interferon alpha 2 | 69 percentage change | Standard Deviation 119 |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-10 | -5 percentage change | Standard Deviation 8 |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-6 | 56 percentage change | Standard Deviation 91 |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum tumor necrosis factor alpha | -29 percentage change | Standard Deviation 11 |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p70 | 23 percentage change | Standard Deviation 40 |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-12p40 | 0 percentage change | Standard Deviation 0 |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-8 | -44 percentage change | Standard Deviation 13 |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum macrophage inflammatory protein-1 alpha | 0 percentage change | Standard Deviation 0 |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum interleukin-1 beta | 0 percentage change | Standard Deviation 0 |
| Part B: Placebo | Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose | Serum monocyte chemoattractant protein-1 | -27 percentage change | Standard Deviation 14 |
Secondary
Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: 0.38 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 8 | 0 participants |
| Part A: 0.38 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 15 | 0 participants |
| Part A: 0.38 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Overall | 0 participants |
| Part A: 0.38 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 22 | 0 participants |
| Part A: 0.38 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 3 | 0 participants |
| Part A: 0.38 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 29 | 0 participants |
| Part A: 1.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 29 | 2 participants |
| Part A: 1.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 8 | 0 participants |
| Part A: 1.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 15 | 0 participants |
| Part A: 1.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 3 | 0 participants |
| Part A: 1.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 22 | 0 participants |
| Part A: 1.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Overall | 2 participants |
| Part A: 2.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 29 | 0 participants |
| Part A: 2.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 8 | 0 participants |
| Part A: 2.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 22 | 0 participants |
| Part A: 2.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Overall | 2 participants |
| Part A: 2.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 15 | 2 participants |
| Part A: 2.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 3 | 0 participants |
| Part A: 3.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 15 | 2 participants |
| Part A: 3.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 3 | 0 participants |
| Part A: 3.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 29 | 0 participants |
| Part A: 3.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 8 | 1 participants |
| Part A: 3.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 22 | 0 participants |
| Part A: 3.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Overall | 3 participants |
| Part A: 4.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 3 | 0 participants |
| Part A: 4.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 22 | 0 participants |
| Part A: 4.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 8 | 4 participants |
| Part A: 4.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Overall | 4 participants |
| Part A: 4.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 29 | 0 participants |
| Part A: 4.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 15 | 0 participants |
| Part A: 5.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Overall | 4 participants |
| Part A: 5.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 22 | 0 participants |
| Part A: 5.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 8 | 4 participants |
| Part A: 5.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 3 | 0 participants |
| Part A: 5.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 29 | 0 participants |
| Part A: 5.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 15 | 0 participants |
| Part A: 6.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 29 | 0 participants |
| Part A: 6.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 15 | 0 participants |
| Part A: 6.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 22 | 0 participants |
| Part A: 6.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Overall | 4 participants |
| Part A: 6.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 3 | 1 participants |
| Part A: 6.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 8 | 3 participants |
| Part A: 7.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 22 | 0 participants |
| Part A: 7.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 29 | 1 participants |
| Part A: 7.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 8 | 2 participants |
| Part A: 7.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 3 | 1 participants |
| Part A: 7.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 15 | 0 participants |
| Part A: 7.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Overall | 4 participants |
| Part A: 8.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 29 | 0 participants |
| Part A: 8.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 22 | 0 participants |
| Part A: 8.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 15 | 0 participants |
| Part A: 8.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Overall | 3 participants |
| Part A: 8.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 3 | 2 participants |
| Part A: 8.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 8 | 1 participants |
| Part A: Placebo | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 15 | 0 participants |
| Part A: Placebo | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 22 | 0 participants |
| Part A: Placebo | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 29 | 0 participants |
| Part A: Placebo | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 8 | 0 participants |
| Part A: Placebo | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Overall | 0 participants |
| Part A: Placebo | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 3 | 0 participants |
| Part B: 2.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 22 | 0 participants |
| Part B: 2.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 3 | 0 participants |
| Part B: 2.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 15 | 0 participants |
| Part B: 2.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 8 | 2 participants |
| Part B: 2.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Overall | 2 participants |
| Part B: 2.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 29 | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 3 | 3 participants |
| Part B: 4.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 15 | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Overall | 3 participants |
| Part B: 4.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 8 | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 29 | 0 participants |
| Part B: 4.0 mg/kg | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 22 | 0 participants |
| Part B: Placebo | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 22 | 0 participants |
| Part B: Placebo | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Overall | 1 participants |
| Part B: Placebo | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 8 | 1 participants |
| Part B: Placebo | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 15 | 0 participants |
| Part B: Placebo | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 29 | 0 participants |
| Part B: Placebo | Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence) | Day 3 | 0 participants |
Secondary
Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days
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.
Time frame: Baseline, up to Day 29, and through 100 days of follow-up
Population: All participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: 0.38 mg/kg | Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days | 4 participants |
| Part A: 1.0 mg/kg | Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days | 4 participants |
| Part A: 2.0 mg/kg | Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days | 4 participants |
| Part A: 3.0 mg/kg | Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days | 4 participants |
| Part A: 4.0 mg/kg | Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days | 4 participants |
| Part A: 5.0 mg/kg | Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days | 4 participants |
| Part A: 6.0 mg/kg | Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days | 4 participants |
| Part A: 7.0 mg/kg | Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days | 4 participants |
| Part A: 8.0 mg/kg | Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days | 4 participants |
| Part A: Placebo | Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days | 18 participants |
| Part B: 2.0 mg/kg | Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days | 4 participants |
| Part B: 4.0 mg/kg | Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days | 3 participants |
| Part B: Placebo | Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days | 4 participants |