Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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ClinicalTrials.gov |
Last refreshed on:
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10 May 2021 |
Main ID: |
NCT03767829 |
Date of registration:
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05/12/2018 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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A Study of ALN-AAT02 in Healthy Participants and Participants With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
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Scientific title:
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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:
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December 5, 2018 |
Target sample size:
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32 |
Recruitment status: |
Terminated |
URL:
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https://clinicaltrials.gov/show/NCT03767829 |
Study type:
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Interventional |
Study design:
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Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
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Phase:
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Phase 1/Phase 2
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Countries of recruitment
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United Kingdom
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Contacts
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Name:
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Medical Director |
Address:
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Telephone:
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Email:
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Affiliation:
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Alnylam Pharmaceuticals |
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Key inclusion & exclusion criteria
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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
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Health Condition(s) or Problem(s) studied
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ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
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Intervention(s)
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Drug: Placebo
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Drug: ALN-AAT02
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Primary Outcome(s)
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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]
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Secondary Outcome(s)
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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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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]
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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]
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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]
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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]
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Fraction Eliminated in Urine (fe) of ALN-AAT02
[Time Frame: Part A: Day 1; Part B: Days 1 and 85]
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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]
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Secondary ID(s)
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2018-001362-41
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ALN-AAT02-001
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Source(s) of Monetary Support
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Please refer to primary and secondary sponsors
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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