Overview

A Study of ALN-AAT02 in Healthy Participants and Participants With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease

Status:
Terminated

Trial end date:
2020-06-25

Target enrollment:
0

Participant gender:
All

Summary

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.

Phase:

Phase 1/Phase 2

Accepts Healthy Volunteers?

Accepts Healthy Volunteers

Details

Lead Sponsor:

Alnylam Pharmaceuticals

Treatments:

Alpha 1-Antitrypsin
Protein C Inhibitor

Criteria

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.