Testing Fazirsiran against a placebo for alpha1-antitrypsin deficiency

Exclusion

• −The participant has a history of hypersensitivity or allergies with any associated excipients of fazirsiran.
• −The participant has human immunodeficiency virus (HIV) infection as shown by the presence of anti-HIV antibody (seropositive).
• −The participant is seropositive for hepatitis B virus (HBV surface antigen positive and/or HBV core antibody positive without HBV surface antibody at screeningScreeningThe checks done before joining, to see whether a study fits.Read more →) or hepatitis C virus (HCV) (detectable HCV Ribonucleic Acid \[RNA\] at screening). Cured HCV (positive antibody test without detectable HCV RNA for at least 6 months after treatment) is acceptable.
• −The participant has evidence of \>= F2 fibrosis based on liver biopsy during the screening period.
• −The participant has a history of liver decompensating events.
• −The participant has a history of varices based on a previous esophagogastroduodenoscopy.
• −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 for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. Participants with curatively treated malignancies who have no evidence of metastatic disease and disease-free interval greater than (\>) 1 year may be enrolledEnrolmentThe number of participants a study plans to include, or has included.Read more → after approval by the medical monitor.
• −The participant has an abnormal finding of clinical relevance at the screening evaluation and before administration of the first dose of study dosing that, in the opinion of the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →, could adversely impact participant safety during the study or adversely impact study results.
• −The participant has any laboratory abnormalities at screening and before the first dose of the study drug that meet protocolProtocolThe detailed plan a study must follow.Read more → parameters.
• −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 recent lower respiratory tract infection, such as pneumonia, within the last 6 months before screening. The participant may be screened earlier based on principal investigator (PI) assessment of clinical recovery and return to baselineBaselineYour starting measurements, taken before treatment begins.Read more → pulmonary function in discussion with the medical monitor.
• −The participant has a history of frequent pulmonary exacerbations (\>=2 moderate or severe 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 or supplemental oxygen with continuous positive airway pressure (CPAP) or bilevel positive airway pressure for acute respiratory failure. The following conditions are allowable for the participant to enter screening: short-term use of oxygen supplementation (example, for the management of acute chronic obstructive pulmonary disease \[COPD\] exacerbation) or CPAP for obstructive sleep apnea.
• −The participant has unstable, poorly controlled, or severe hypertension. Participants may be rescreened once their blood pressure (BP) is successfully controlled.
• −The participant has a history of torsades de pointes, ventricular rhythm disturbances (example, ventricular tachycardia), heart block (excluding first-degree block, being PR interval prolongation only), congenital long QT syndrome or new ST-segment elevation or depression or a 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), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction less than \[\<\] 20 percent \[%\]), transient ischemic attack, or cerebrovascular accident within 6 months before screening.
• −The participant has a history of more than moderate alcohol consumption within 12 months 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 RNA interference (RNAi) for alpha-1 antitrypsin deficiency-associated liver disease (AATD-LD).
• −The participant has received an investigational agent or device within 30 days, or 5 half-lives, whichever is longer, before the dosing of study medication or is currently participating in an investigational study involving a therapeutic intervention.
• −The participant has donated \>=500 milliliter (mL) of blood within 1 month of the administration of study treatment.
• −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, pulmonary, neurologic, psychiatric, gastrointestinal (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 inclusionInclusion criteriaThe things you must have or be for a study to consider you.Read more → into the study.
• −The participant has a history of thromboembolic disease (including deep vein thrombosis or pulmonary embolism), within 6 months before screening, or is taking chronic anticoagulants.
• −This 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 sponsorSponsorThe organisation responsible for the study overall.Read more → 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 siteTrial siteA hospital or clinic where a study is actually run.Read more → employee involved in the conduct of this study, an immediate family member (example, spouse, parent, child, sibling), is in a dependent relationship with study site employee who is involved in the conduct of this study or may consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more → under duress.
• −The participant takes or is required to take excluded medications.
• −The participant is pregnant or breastfeeding or intending to become pregnant before participating in this study, during the study, or within 6 months after last dose of the study drug; or the participant is intending to donate ova during such time period.
• −The participant has a history of major surgery within 12 weeks of screening (or longer, at the discretion of the investigator).