A Study About Fazirsiran in People With and Without Liver Problems

Inclusion criteria

Key Inclusion Criteria for All Participants

• A 12-lead ECG at screening that, in the opinion of the investigator, has no abnormalities that compromise the participant's safety in this study.
• No abnormal finding of clinical relevance at screening or before dosing that in the opinion of the investigator could adversely impact participant safety during the study or adversely impact study results.

Key Inclusion Criteria for Participants with Hepatic Impairment:

• The participant is 18 to 75 years of age inclusive at the time of signing the informed consent form (ICF).
• The participant has a body mass index (BMI) greater than or equal to (>=) 18.0 and less than or equal to (<=) 40.0 kilograms per square meter (kg/m^2) at screening.
• Aside from HI, the participant must be sufficiently healthy for study participation based upon medical history, physical examination, vital signs, electrocardiograms (ECGs), and screening clinical laboratory profiles, as deemed by the investigator or designee.
• Diagnosis of chronic (example, imaging, biopsy, etc.) stable hepatic insufficiency for at least 3 months before screening with features of cirrhosis due to any etiology according to medical history. HI must be stable, that is, no significant changes in hepatic function or clinical status in the 30 days preceding screening (or since the last visit if within 3 months before screening) and with treatment with stable doses of medication.
• Has a Child-Turcotte-Pugh (CTP) score confirmed by 2 tests as follows:
• Arm 1: Mild HI, CTP Class A: >=5 and <=6
• Arm 2: Moderate HI, CTP Class B: >=7 and <=9
• Arm 3: Severe HI, CTP Class C: >=10 and <=15
• It must be confirmed that the participant does not have hepatocellular carcinoma (HCC).

Key Inclusion Criterion for Participants with Mild Hepatic Impairment • The participant has pulmonary status meeting criteria of percent predicted forced expiratory volume in the first second of expiration (ppFEV1) >=80 percent and percent predicted diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (ppDLCOhgb) >=75%, based on pulmonary function test (PFT) at screening conducted as per American Thoracic Society (ATS)-European Respiratory Society (ERS) criteria.

Key Inclusion Criterion for Participants with Moderate and Severe Hepatic Impairment

• The participant has pulmonary status meeting the criteria defined in the protocol based on PFT at screening conducted as per ATS-ERS criteria.

Key Inclusion Criteria for Participants with Normal Hepatic Function

• The participant is 18 to 85 years of age inclusive, at the time of signing the ICF.
• The participant has a BMI >=18.0 and <=40.0 kg/m^2, at screening. Participants will be matched to participants with HI by BMI (±15%).
• AAT level at or above the lower end of the reference range (above or equal to 16.6 micromole (mcM) or 90 milligram per deciliter [mg/dL]) at screening.
• The participant has normal liver tests including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBILI) <=1.2 x upper limit of the normal range (ULN) at screening and check-in.
• The participant has pulmonary status meeting criteria of ppFEV1 >=80%, and ppDLCOhgb >=75%, based on PFT at screening conducted as per ATS- ERS criteria.

Exclusion criteria

Key Exclusion Criteria for All Participants:

• The participant has uncontrolled hypertension (systolic blood pressure [BP] >170 mm Hg and diastolic BP >100 millimeter of mercury [mmHg] at screening). Participants may be rescreened once BP is successfully controlled.
• The participant has a history of torsades de pointes, ventricular rhythm disturbances (example, ventricular tachycardia or fibrillation), heart block (excluding first-degree block, being pulse rate [PR] interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG. Participants with a history of atrial arrhythmias should be discussed with the medical monitor.
• The participant has symptomatic heart failure (per New York Heart Association guidelines) or severe heart failure with reduced ejection fraction (EF <20%), unstable angina, myocardial infarction, transient ischemic attack, or cerebrovascular accident within 6 months before screening.
• The participant is expected to have severe and unavoidable high-level exposure to inhaled pulmonary toxins during the study.
• The participant has had a recent lower respiratory tract infection, such as pneumonia, within the last 6 months before screening.
• The participant has a history of malignancy within the last 1 year, except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. Participants with other curatively treated malignancies who have no evidence of metastatic disease and have been disease-free for >1 year may enter the study after approval by the medical monitor.
• The participant has a history of thromboembolic disease (including deep vein thrombosis or pulmonary embolism) within 6 months of screening.

Key Exclusion Criteria for Participants with Hepatic Impairment:

• The participant has a history of gastric or esophageal variceal bleeding within the past 6 months of dosing and for which varices have not been adequately treated with medication and/or endoscopic procedures.
• The participant has grade >2 hepatic encephalopathy assessed using the West Haven criteria.
• The participant has evidence of hepatopulmonary syndrome or portal-pulmonary hypertension.
• The participant has portal vein thrombosis, transjugular intrahepatic portosystemic shunt (TIPS), or surgical portosystemic shunt.
• The participant has required endoscopic treatment of esophageal or gastric varices or paracentesis to control ascites within the last 3 months of dosing.
• The participant has chronic hepatitis B (hepatitis B surface antigen positive, or positive for both hepatitis B surface antibody and hepatitis B core antibody but negative for hepatitis B surface antigen); or has chronic or incompletely or unsuccessfully treated hepatitis C (as demonstrated by a positive hepatitis C antibody and positive polymerase chain reaction [PCR]).
• The participant has any of the following clinically significant abnormal parameters at screening:

• ALT or AST levels >250 units per liter (U/L) at screening.
• Estimated glomerular filtration rate <45 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2).