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

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

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.

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