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A Study of ALN-AAT02 in Healthy Participants and Participants With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease | Clinical Trials | Clareo Health

TERMINATEDPHASE1/PHASE2

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

A Phase 1/2, Randomized, Double-blind, Placebo-controlled, Single-ascending and Multiple-dose, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN-AAT02 in Healthy Adult Subjects and Patients With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease

NCT03767829•Alnylam Pharmaceuticals

View on ClinicalTrials.gov

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.

Eligibility

Age

18 - 65 years

Sex

ALL

Healthy Volunteers

Yes

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;
+2 more criteria

Locations (1)

Clinical Trial Site

London, United Kingdom

Key Dates

Start Date

December 5, 2018

Primary Completion Date

June 25, 2020

Completion Date

June 25, 2020

Last Updated

April 27, 2021

Enrollment

ACTUAL participants

Conditions

ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease

Interventions

ALN-AAT02

DRUG

Placebo

DRUG

ALN-AAT02

DRUG