The sponsor decided not to proceed with Part B for business reasons.

The purpose of this study is to evaluate the safety and tolerability of single or multiple doses of ALN-AAT02. The study will be conducted in 2 sequential phases in which Part A will be a single-ascending dose (SAD) phase in healthy participants, and Part B will be a multiple-ascending dose (MAD) phase in participants with ZZ type alpha-1 antitrypsin deficiency (PiZZ) and biopsy-proven alpha-1 antitrypsin (AAT) deficiency-associated liver disease.

Inclusion Criteria:

• Male or female, aged 18 to 65 years, inclusive;
• Has normal 12-lead electrocardiogram (ECG);
• Has body mass index (BMI) between 18 and 30 kg/m^2, inclusive;
• Has been a nonsmoker for at least 5 years before screening;
• Part A only: Has Alpha-1 antitrypsin (AAT) levels within normal limits;
• Part A only: Has adequate Forced Expiratory Volume in 1 second (FEV1) and adequate FEV1/forced vital capacity ratio;
• Part B only: Has documented ZZ type AAT by genotype;
• Part B only: Has liver biopsy within 90 days of the first dose of study drug demonstrating ZZ type alpha-1 antitrypsin deficiency (PiZZ AATD) liver disease;
• Part B only: Has adequate post-bronchodilator FEV1 and adequate diffusing capacity of the lung for carbon monoxide;
• Part B only: If on any maintenance medication, is likely to be able to remain on a stable medication regimen for the duration of the study (no new medications within 30 days prior to first dose of study drug).

Exclusion Criteria:

• Has known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) infection;
• Has clinically significant abnormal laboratory results;
• Received an experimental drug within 30 days of dosing;
• Has a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc);
• Part A only: Has estimated glomerular filtration equal to or below 60 mL/min/1.73 m^2 at screening;
• Part A only: Has a history of asthma or recurrent or chronic lung disease, excluding resolved childhood asthma;
• Part A only: Has a history of chronic liver disease;
• Part B only: Has estimated glomerular filtration equal to or below 45 mL/min/1.73 m^2 at screening;
• Part B only: Received an augmentation therapy for AAT deficiency within 8 weeks of first dose of study drug;
• Part B only: Has a history of chronic liver disease from any known cause other than ZZ type AAT deficiency;
• Part B only: Has a history of hepatic encephalopathy;
• Part B only: Has a history of gastrointestinal bleeding or ascites.