An Extension Study to Learn About the Long-Term Safety of Fazirsiran and if Fazirsiran Can Help People With Alpha-1 Antitrypsin Liver Disease

Exclusion Criteria

• •The participant is likely to require major surgery. Major surgery typically requires at least 1 night in the hospital. Examples include laparoscopic surgery (except cholecystectomy and tubal ligation); Gastrointestinal tract (GI) tract surgery including 1 or more segments of the colon or terminal ileum; open resection of organs; large joint replacements; mastectomy with reconstruction; and spine, thoracic, vascular, or intracranial surgery.
• •The participant has evidence of other forms of chronic liver diseases, including viral hepatitis B or C, primary biliary cholangitis, primary sclerosing cholangitis, Wilson disease, alcoholic hepatitis, hemochromatosis, liver cancer, history of biliary diversion, or autoimmune hepatitis.
• •The participant has abnormal finding(s) of clinical relevance during the evaluation before the first study dosing that, in the opinion of the investigator, could adversely impact participant safety during the study or adversely impact study results. For US only: Participants with baseline emphysema may be allowed into the OLE if their lung disease has been stable.
• •The participant had major protocol deviation(s) in AROAAT2001 or AROAAT2002 that would affect the conduct of this study.
• •The participant permanently discontinued investigational product because of an AE, adjudicated as related to the study intervention, in AROAAT2001 or AROAAT2002.
• •Female participants who became pregnant during Study AROAAT2001 or AROAAT2002, female participants who are lactating or planning to become pregnant during the study period; or males or female participants of childbearing potential not agreeing to continue using appropriate contraception methods through the conclusion of study participation.
• •The participant has a Child-Turcotte-Pugh (CTP) score \>=7 OR (Model for End-Stage Liver Disease) MELD score \>14.
• •Participants who have a newly-diagnosed malignancy or recurrence of malignancy (except for resected cutaneous basal cell carcinoma, squamous cell carcinoma, superficial bladder tumors, or carcinoma in situ of the uterine cervix that has been treated with no evidence of recurrence).
• •The participant is experiencing a pulmonary exacerbation at the time of enrollment (participant enrollment may be temporarily delayed after the clinical resolution of an exacerbation).
• •The participant has unstable, poorly controlled, or severe hypertension. Participants may be reevaluated once their blood pressure is successfully controlled.
• •The participant has a history of more than moderate alcohol consumption within 12 months before the Day 1 visit.
• •The participant has a history of hypersensitivity or allergies to fazirsiran or any associated excipients.
• •The participant has any concomitant medical or psychiatric condition or social situation that would make it difficult to comply with protocol requirements or put the participant at additional safety risk.
• •The participant has a history of clinically significant hematologic, renal, hepatic, cardiovascular, infectious, pulmonary, neurologic, psychiatric, GI, systemic inflammatory, metabolic, or endocrine disorder or any other condition that, in the opinion of the investigator, rendered the participant a poor candidate for inclusion into the study.
• •The participant has a history of thromboembolic disease (including deep vein thrombosis or pulmonary embolism), within 24 weeks before enrollment; or is taking chronic anticoagulants. (Note: Participants taking stable doses of chronic anticoagulants may be allowed after consultation with the medical monitor, if they do not have cirrhosis or a history of liver decompensating events).
• •The participant is unable to return for all scheduled study visits.
• •The participant has known or suspected coronavirus disease 2019 (COVID-19) that in the opinion of the sponsor and investigator does not resolve during screening. Positive antibody testing for COVID-19 without other evidence of current or recent active infection does not exclude participation. Enrollment of participants who fail inclusion due to COVID-19 infection may be temporarily delayed at the discretion of the sponsor and investigator. If the participant has a positive polymerase chain reaction (PCR) with no other evidence of infection, a retest may be allowed; however, to enroll in the study the participant must have a negative PCR.
• •The participant is a study site employee, an immediate family member (for example, spouse, parent, child, sibling), or is in a dependent relationship with a study site employee who is involved in conduct of this study, or may consent under duress.
• •The participant who, in the opinion of the investigator or the sponsor, will be uncooperative or unable to comply with study procedures.
• •The participant who participates in other studies involving an investigational product.