Study to Learn About the Safety of Fazirsiran and if it Can Help People With Alpha-1 Antitrypsin Liver Disease With Mild Liver Scarring (Fibrosis)

Inclusion Criteria:

• In the opinion of the investigator, the participant is capable of understanding andfully complying with the protocol requirements and adhering to the protocolschedule.

• The participant is able to read, understand, and complete the study questionnaireselectronically per the investigator's judgment.

• The participant signs and dates a written Informed Consent Form (ICF). Any requiredprivacy authorization should also be signed before the initiation of any studyprocedures.

• The participant, of any sex, is aged 18 to 75 years, inclusive.

• The participant must have a diagnosis of the protease inhibitor Z mutation (PiZZ)genotype AATD. A diagnosis of PiZZ from source-verifiable medical records ispermitted. Otherwise, participants must undergo PiZZ confirmatory testing (genotyping for PiS and PiZ alleles) at screening. PiMZ or PiSZ genotypes are notpermitted.

• The participant's liver biopsy core samples collected as per protocol requirements.

• The participant has evidence of METAVIR stage F1 liver fibrosis, evaluated by acentrally read baseline liver biopsy during the screening period; or confirmed asmeeting all the entry criteria by central reading from a previous biopsy conductedwithin 1 year before the screening period using an adequate liver biopsy and slidesas defined in the study laboratory manual.

• The participant has a pulmonary status that meets the protocol requirements.

• It must be confirmed that the participant does not have hepatocellular carcinoma (HCC).

• Participants must have a negative coronavirus disease 2019 (COVID-19) polymerasechain reaction (PCR) test at screening.

• Any participant who is taking statins, angiotensin-converting enzyme inhibitors,angiotensin II receptor blockers, or beta-1 selective adrenergic receptor inhibitorsmust have been receiving a stable dose of these medications for at least 8 weeksbefore randomization. All attempts are to be made for the participant to continuethe same dose of the medication for the duration of study participation.

• An adult participant must have a body mass index (BMI) between 18 and 39 kilogramper meter square (kg/m^2), inclusive.

• The participant has a 12-lead electrocardiogram at screening that, in the opinion ofthe investigator, has no abnormalities that could compromise the participant'ssafety in this study.

• The participant is a nonsmoker.

• If the participant was being treated with any respiratory medications includinginhaled bronchodilators, inhaled anticholinergics, inhaled corticosteroids, orlow-dose systemic corticosteroids (prednisone less than or equal to (<=10)milligrams per day (mg/d) or its equivalent), the doses of the participant'smedications must have remained unchanged for at least 14 days before screening.

• The participant must have suitable venous access for blood sampling.

• A person of childbearing potential (POCBP) must have a negative serum pregnancy testat screening and a negative urine pregnancy test on Day 1 before dosing.

• The participant must use appropriate contraception methods (that is, highlyeffective methods for female and medically appropriate methods for male studyparticipants) for the entire duration of the study and for 24 weeks after the lastdose of study medication. The participant must not donate sperm for at least 24weeks after the last dose of study medication.

Exclusion criteria:

• The participant has evidence of greater than or equal to (>=) F2 fibrosis based onliver biopsy during the screening period.

• The participant has a history of liver decompensating events.

• The participant has a history of varices based on a previousesophagogastroduodenoscopy.

• The participant has portal vein thrombosis.

• The participant has undergone a prior trans-jugular portosystemic shunt procedure.

• The participant has evidence of other forms of chronic liver diseases.

• The participant has a history of malignancy within the last 5 years, except foradequately treated basal cell carcinoma, squamous cell skin cancer, superficialbladder tumors, or in situ cervical cancer. Participants with curatively treatedmalignancies who have no evidence of metastatic disease and disease-free intervalgreater than (>) 1 year may be enrolled after approval by the medical monitor.

• The participant has an abnormal finding of clinical relevance at the screeningevaluation and before administration of the first dose of study dosing that, in theopinion of the investigator, could adversely impact participant safety during thestudy or adversely impact study results.

• The participant has any laboratory abnormalities at screening and before the firstdose of the study drug that meet protocol parameters.

• The participant is expected to have severe and unavoidable high-level exposure toinhaled pulmonary toxins during the study such as may occur with occupationalexposure to mineral dusts or metals.

• The participant has a recent lower respiratory tract infection, such as pneumonia,within the last 24 weeks before screening.

• The participant has a history of frequent pulmonary exacerbations (>=2 moderate orsevere exacerbations within 52 weeks before screening).

• The participant is experiencing a pulmonary exacerbation at the time of screening (participant may be rescreened after the clinical resolution of an exacerbation).

• The participant is receiving long-term, around-the-clock oxygen supplementation orsupplemental oxygen with continuous positive airway pressure (CPAP) or bilevelpositive airway pressure for acute respiratory failure. The following conditions areallowable for the participant to enter screening: short-term use of oxygensupplementation (example, for the management of acute chronic obstructive pulmonarydisease [COPD] exacerbation) or CPAP for obstructive sleep apnea.

• The participant has human immunodeficiency virus (HIV) infection as shown by thepresence of anti-HIV antibody (seropositive).

• The participant is seropositive for hepatitis B virus (HBV surface antigen positiveand/or HBV core antibody positive without HBV surface antibody at screening) orhepatitis C virus (HCV) (detectable HCV Ribonucleic Acid [RNA] at screening). CuredHCV (positive antibody test without detectable HCV RNA for at least 24 weeks aftertreatment) is acceptable.

• The participant has unstable, poorly controlled, or severe hypertension.Participants may be rescreened once their blood pressure (BP) is successfullycontrolled.

• The participant has a history of torsades de pointes, ventricular rhythmdisturbances (example, ventricular tachycardia), heart block (excluding first-degreeblock, being PR interval prolongation only), congenital long QT syndrome or newST-segment elevation or depression or a new Q wave on ECG. Participants with ahistory of atrial arrhythmias should be discussed with the medical monitor.

• The participant has symptomatic heart failure (per New York Heart Associationguidelines), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction less than [<] 20 percent [%]), transient ischemic attack, orcerebrovascular accident within 24 weeks before screening.

• The participant has a history of major surgery within 12 weeks of screening (orlonger, at the discretion of the investigator).

• The participant has a history of more than moderate alcohol consumption within 12months before the screening visit.

• The participant has a history of drug abuse (such as cocaine, phencyclidine) within 1 year before the screening visit or has a positive urine drug screen at screening.

• The participant has previously been treated with fazirsiran or any other RNAinterference (RNAi) for alpha-1 antitrypsin deficiency-associated liver disease (AATD-LD).

• The participant has a history of hypersensitivity or allergies with any associatedexcipients of fazirsiran.

• The participant has received an investigational agent or device within 30 days, or 5half-lives, whichever is longer, before the dosing of study medication or iscurrently participating in an investigational study involving a therapeuticintervention.

• The participant has donated >=500 milliliter (mL) of blood within 1 month of theadministration of study treatment.

• The participant has any concomitant medical or psychiatric condition or socialsituation that would make it difficult to comply with protocol requirements or putthe participant at additional safety risk. The participant has a history ofclinically significant hematologic, renal, hepatic, pulmonary, neurologic,psychiatric, gastrointestinal (GI), systemic inflammatory, metabolic, or endocrinedisorder or any other condition that, in the opinion of the investigator, renderedthe participant a poor candidate for inclusion into the study.

• The participant has a history of thromboembolic disease (including deep veinthrombosis or pulmonary embolism), within 24 weeks before screening, or is takingchronic anticoagulants.

• This participant is unable to return for all scheduled study visits.

• The participant has known or suspected COVID-19 by the investigator within the past 2 months before screening. Positive antibody testing for COVID-19 without otherevidence of current or recent active infection does not exclude participation.Participants who were in screening at the time that COVID-19-related factorsresulted in discontinuation may also be rescreened with approval of the sponsor ordesignee.

• The participant is a study site employee, an immediate family member (example,spouse, parent, child, sibling), or is in a dependent relationship with study siteemployee who is involved in the conduct of this study or may consent under duress.

• The participant takes or is required to take excluded medications.

• The participant is pregnant or breastfeeding or intending to become pregnant beforeparticipating in this study, during the study, and within 24 weeks after last doseof the study drug; or the participant is intending to donate ova during such timeperiod.