A Randomized, Double-blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Fazirsiran in the Treatment of Alpha-1 Antitrypsin Deficiency–Associated Liver Disease With METAVIR Stage F2 to F4 Fibrosis
This research study of fazirsiran (FAZ-i-sir-an; also called TAK-999 or the “study drug”) because you have alpha-1 antitrypsin deficiency-associated liver disease (AATD LD) with METAVIR stage F2 to F4 fibrosis (METAVIR is a system used to score the amount of inflammation and fibrosis seen in a liver biopsy). In AATD, abnormal (Z-AAT) proteins build up in liver cells, leading to varying amounts of liver problems. The goal of treatment with fazirsiran is to prevent and improve the build up of these abnormal proteins that cause liver injury and fibrosis
-The total amount of time you may be involved in the study is about 4 ½ years (230 weeks). -Screening Period of up to 70 days. -Treatment Period of 196 weeks or about 4 years. During the study, you will get the study drug or placebo at the study site. -Follow-up Period of 6 months. You will have visits 6, 12, and 24 weeks after your last injection of the study drug or placebo. -You will have lung function tests (PFT and DLCO) to check how your lungs are working At every visit during the treatment period you will have: -Your vital signs will be measured, this includes your heart rate, blood pressure, breathing rate, temperature, and amount of oxygen in your blood. -You will have a brief physical exam. -Your weight will be measured. -You will have an ECG. -Collect lab samples During specific study visits during the treatment period the following tests will be performed: -An abdominal ultrasound -FibroScan -CT scans You will complete questionnaires.
The participant must use highly effective contraception
The participant must have suitable vein access for blood sampling
Participant agrees not to smoke at any time during the study.
The participant must have a diagnosis of the PiZZ genotype AATD
The participant has a recent lower respiratory tract infection, such as pneumonia, within the last 6 months before screening.
The participant is expected to have severe and unavoidable high-level exposure to inhaled pulmonary toxins during the study such as may occur with occupational exposure to mineral dusts or metals.
The participant has a history of malignancy within the last 5 years
The participant has evidence of other forms of chronic liver diseases