This is a multicenter, parallel-group, double-blind, randomized phase 4 study designed to identify the optimal dose of CE1226 (2 active doses) to slow disease progression as assessed by reduced rates of annual lung density decline in alpha-1 antitrypsin (AAT) deficient participants over 3 years as compared with the marketed dose 60 milligrams per kilogram (mg/kg).
• Age greater than or equal to (>=) 18 and less than or equal to (<=) 65 years at the time of providing written informed consent.
• Confirmed diagnosis of emphysema related to AATD with either the PiZZ, PiZ(null), or Pi(null/null) genotype with documented serum AAT levels less than (<) 11 micrometer (μM) (or < 50 mg/dL [milligram/deciliter]) at any time before the first administration of CE1226 on Day 1 (Baseline).
• Participants should not have acute illness or pulmonary exacerbation within 6 weeks before the first administration of CE1226 on Day 1 (Baseline).
• Participants should not have previously received gene therapy for AATD at any point.
• Participants with liver disease secondary to AATD.