Efficacy and Safety of CSL222 (Etranacogene Dezaparvovec) Gene Therapy in Adults With Hemophilia B With Pretreatment Adeno-associated Virus Serotype 5 (AAV5) Neutralizing Antibodies (Nabs)

Inclusion Criteria:

• Age ≥ 18 years and considered legally an adult, as defined by country regulations.

• Has congenital hemophilia B with known severe or moderately severe FIX deficiency (≤ 2% of normal circulating FIX) for which the participant is on continuous routine FIXprophylaxis

• Has 2 consecutive detectable AAV5 NAb titer results between Screening and VisitL-Final using a validated AAV5 NAb assay (based on central laboratory results)

• Has > 150 previous exposure days to FIX replacement therapy

• Has been on stable FIX prophylaxis for at least 2 months before Screening

• Has demonstrated capability to independently, accurately, and in a timely mannercomplete the eDiary during the Lead-in Period, as judged by the investigator

• Acceptance to barrier contraception protection for 1 year starting the day of CSL222treatment.

• Able to provide informed consent after receipt of verbal and written informationabout the study

• Investigator believes that the participant (or the participant's legally acceptablerepresentative[s]) understands the nature, scope, and possible consequences of thestudy and is able to adhere to the study procedures.

Exclusion Criteria:

• History of FIX inhibitors or positive FIX inhibitor test at Prescreening, Screeningor Visit L Final (based on central laboratory results).

• Screening or Visit L-Final laboratory values that meet the definition of SevereHepatic Impairment per Common Terminology Criteria for Adverse Events (CTCAE) (basedon central laboratory results)

• ALT > 2 × the ULN at Screening or Visit L-Final laboratory values (based on centrallaboratory results).

• Any condition other than hemophilia B resulting in an increased bleeding tendency.

• Thrombocytopenia, defined as a platelet count below 50 × 10^9/L, at Screening orVisit L Final (based on central laboratory results).

• Any uncontrolled or untreated infection (human immunodeficiency virus [HIV],hepatitis B virus [HBV] and hepatitis C virus [HCV], or any other significantconcurrent, uncontrolled medical condition including, but not limited to, renal,hepatic, cardiovascular, hematological, gastrointestinal, endocrine, pulmonary,neurological, cerebral or psychiatric disease, alcoholism, drug dependency, or anyother psychological disorder evaluated by the investigator to interfere withadherence to the clinical study protocol procedures or with the degree of toleranceto CSL222.

• Known history of allergy to corticosteroids or known medical condition that wouldrequire chronic administration of oral corticosteroids.

• Known uncontrolled allergic conditions or allergy / hypersensitivity to anycomponent of the CSL222 excipients (ie, sucrose, potassium chloride, potassiumdihydrogen phosphate, sodium chloride, and disodium hydrogen phosphate).

• Previous gene therapy treatment.

• Receipt of an experimental agent or device within 60 days before Screening until theend of the study.