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

• Register: ClinicalTrials.gov
• Last refreshed on: 10 May 2021
• Main ID: NCT03767829
• Date of registration: 05/12/2018
• Prospective Registration: Yes
• Primary sponsor: Alnylam Pharmaceuticals
• Public title: A Study of ALN-AAT02 in Healthy Participants and Participants With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
• Scientific title: 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
• Date of first enrolment: December 5, 2018
• Target sample size: 32
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03767829
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1/Phase 2

Countries of recruitment

United Kingdom

Contacts

• Name: Medical Director
• Affiliation: Alnylam Pharmaceuticals

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease

Intervention(s)

Drug: Placebo

Drug: ALN-AAT02

Primary Outcome(s)

Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) [Time Frame: Part A: up to approximately 12 months; Part B: up to approximately 18 months]

Secondary Outcome(s)

Amount of Full Length Drug Excreted in Urine (Ae) of ALN-AAT02 [Time Frame: Part A: Day 1; Part B: Days 1 and 85]

Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ALN-AAT02 [Time Frame: Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87]

Change From Baseline in Serum Levels of Alpha-1 Antitrypsin (AAT) [Time Frame: Part A: baseline up to Day 85 and every 84 days up to approximately 12 months; Part B: baseline up to Day 169 and every 84 days up to approximately 18 months]

Apparent Terminal Elimination Half-life (t1/2) for ALN-AAT02 [Time Frame: Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87]

Maximum Observed Plasma Concentration (Cmax) for ALN-AAT02 [Time Frame: Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87]

Fraction Eliminated in Urine (fe) of ALN-AAT02 [Time Frame: Part A: Day 1; Part B: Days 1 and 85]

Time to Reach Cmax (tmax) for ALN-AAT02 [Time Frame: Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87]

Secondary ID(s)

2018-001362-41

ALN-AAT02-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors