A Study of ALN-AAT02 in Healthy Participants and Participants With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
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ClinicalTrials.gov Identifier: NCT03767829 |
Recruitment Status :
Terminated
(The sponsor decided not to proceed with Part B for business reasons.)
First Posted : December 7, 2018
Last Update Posted : April 27, 2021
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Condition or disease | Intervention/treatment | Phase |
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ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease | Drug: ALN-AAT02 Drug: Placebo | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 32 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Double (Participant, Investigator) |
Primary Purpose: | Treatment |
Official 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 |
Actual Study Start Date : | December 5, 2018 |
Actual Primary Completion Date : | June 25, 2020 |
Actual Study Completion Date : | June 25, 2020 |

Arm | Intervention/treatment |
---|---|
Experimental: Part A: SAD: ALN-AAT02
Participants will be administered a single dose of ALN-AAT02.
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Drug: ALN-AAT02
ALN-AAT02 will be administered subcutaneously (SC) at dose levels planned for Part A. |
Placebo Comparator: Part A: SAD: Placebo
Participants will be administered a single dose of matching placebo.
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Drug: Placebo
Sterile normal saline (0.9% NaCl) matching volume of ALN-AAT02 doses will be administered SC. |
Experimental: Part B: MAD: ALN-AAT02
Participants will be administered multiple doses of ALN-AAT02.
|
Drug: ALN-AAT02
ALN-AAT02 will be administered subcutaneously (SC). Part B dose levels to be determined upon review of data from Part A. |
Placebo Comparator: Part B: MAD: Placebo
Participants will be administered multiple doses of matching placebo.
|
Drug: Placebo
Sterile normal saline (0.9% NaCl) matching volume of ALN-AAT02 doses will be administered SC. |
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- Fraction Eliminated in Urine (fe) of ALN-AAT02 [ Time Frame: Part A: Day 1; Part B: Days 1 and 85 ]
- Amount of Full Length Drug Excreted in Urine (Ae) of ALN-AAT02 [ Time Frame: Part A: Day 1; Part B: Days 1 and 85 ]

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Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts 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;
- Part B only: Has a history of hepatic encephalopathy;
- Part B only: Has a history of gastrointestinal bleeding or ascites.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03767829
United Kingdom | |
Clinical Trial Site | |
London, United Kingdom |
Study Director: | Medical Director | Alnylam Pharmaceuticals |
Responsible Party: | Alnylam Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT03767829 |
Other Study ID Numbers: |
ALN-AAT02-001 2018-001362-41 ( EudraCT Number ) |
First Posted: | December 7, 2018 Key Record Dates |
Last Update Posted: | April 27, 2021 |
Last Verified: | April 2021 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Liver Diseases Alpha 1-Antitrypsin Deficiency Digestive System Diseases Lung Diseases Respiratory Tract Diseases |
Genetic Diseases, Inborn Subcutaneous Emphysema Emphysema Pathologic Processes |