Study of ARO-AAT in Normal Adult Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-AAT in healthy adult volunteers.

Official Title
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A Phase 1 Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Effect of ARO-AAT on Serum Alpha-1 Antitrypsin Levels in Normal Adult Volunteers

Conditions
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Alpha 1-Antitrypsin Deficiency

Intervention / Treatment
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* Drug: ARO-AAT Injection
* Other: Sterile Normal Saline (0.9% NaCl)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception Willing to provide written informed consent and to comply with study requirements Non-smoker for at least one year Normal lung function No abnormal finding of clinical relevance at Screening Normal AAT level at Screening visit Exclusion Criteria: Clinically significant health concerns Regular use of alcohol within one month prior to Screening Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study Recent use of illicit drugs Use of any drugs or dietary/herbal supplements know to interfere with liver metabolism NOTE: additional inclusion/exclusion criteria may apply, per protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ARO-AAT<br> | Drug: ARO-AAT Injection<br>* Single or multiple doses of ARO-AAT by subcutaneous (sc) injections<br>|
| Placebo Comparator: Placebo<br> | Other: Sterile Normal Saline (0.9% NaCl)<br>* Calculated volume to match active comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) Possibly or Probably Related to Treatment |  | Part A (single-ascending dose [SAD] phase): up to 29 (+/- 2) days post-dose; Part B (multiple-ascending dose [MAD] phase): up to 113 (+/- 2) days post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of ARO-AAT: Maximum Observed Plasma Concentration (Cmax) |  | Part A (single-ascending dose [SAD] phase): up to 48 hours post-dose; Part B (multiple-ascending dose [MAD] phase): up to 48 hours post-dose | 
| PK of ARO-AAT: Time to Maximum Plasma Concentration (Tmax) |  | Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose | 
| PK of ARO-AAT: Terminal Elimination Half-Life (t½) |  | Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose | 
| PK of ARO-AAT: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) |  | Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose | 
| PK of ARO-AAT: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) |  | Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose | 
| Percent Change in Serum Alpha-1 Antitrypsin (AAT) Levels From Day 1 Pre-Dose Baseline to Nadir |  | Part A (SAD phase): up to 29 (+/- 2) days; Part B (MAD phase): up to 113 (+/- 2) days | 
| Duration of Response of Serum AAT levels From Nadir Back to Above 20% of Baseline or Above 90 mg/dL |  | Part A (SAD phase): up to 29 (+/- 2) days; Part B (MAD phase): up to 113 (+/- 2) days |