A Study of an Investigational Drug, ALN-AAT, in Healthy Adult Subjects and Patients With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease

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 Subcutaneously Administered ALN-AAT in Healthy Adult Subjects and Patients with ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease.

Official Title
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A Phase 1/2, Randomized, Single-blind, Placebo-Controlled, Single Ascending Dose and Multiple Dose, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Subcutaneously Administered ALN-AAT in Healthy Adult Subjects and Patients With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease

Conditions
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Antitrypsin Deficiency Liver Disease

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adequate complete blood counts, liver and renal function. 12-lead electrocardiogram (ECG) within normal limits Female subjects must be of non-childbearing potential; e.g. post-menopausal or pre-menopausal with surgical sterilization Male subjects agree to use appropriate contraception Willing to provide written informed consent and willing to comply with study requirements Nonsmokers for at least 5 years before screening Exclusion Criteria: Any uncontrolled or serious disease, or any medical or surgical condition, that may interfere with participation in the clinical study and/or put the subject at significant risk Received an investigational agent within 90 days before the first dose of study drug or are in follow-up of another clinical study Active serious mental illness or psychiatric disorder requiring current pharmacological intervention History or evidence of alcohol or drug abuse within 12 months before screening. History of intolerance to SC injection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ALN-AAT<br> | Drug: ALN-AAT<br>* Single or multiple doses of ALN-AAT by subcutaneous (sc) injection<br>|
| Placebo Comparator: Sterile Normal Saline (0.9% NaCl)<br> | Drug: 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 |
| --- | --- | --- |
| The safety of ALN-AAT evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation |  | Part A (SAD phase): through day 70; Part B (MAD) phase: through Day 154; Part C: through Day 224 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profile of Pharmacokinetics (PK) of ALN-AAT | Cmax, tmax, AUC, t1/2 | Part A (SAD) phase: up to 21 days; Part B (MAD) phase: up to 105 days; Part C: up to 161 days | 
| The effect of ALN-AAT on serum levels of AAT protein |  | Part A (SAD) phase: through day 70; Part B (MAD) phase: through Day 154; Part C: through Day 224 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RNAi therapeutic, AAT, Alpha-1 Antitrypsin Deficiency