The purpose of this study is to assess the risk of bleeding due to failure of expected pharmacological action of CSL222 in adults with severe or moderately severe hemophilia B with detectable pretreatment AAV5 Nabs.
Considered legally an adult, as defined by country regulations.
Has congenital hemophilia B with known severe or moderately severe FIX deficiency (less than or equal to [<=] 2% of normal circulating FIX) for which the participant is on continuous routine FIX prophylaxis.
Has 2 consecutive detectable AAV5 NAb titer results between Screening and Visit L-Final using a validated AAV5 NAb assay (based on central laboratory results).
Has greater than (>) 150 previous exposure days to FIX replacement therapy.
• History of FIX inhibitors or positive FIX inhibitor test at Prescreening, Screening or Visit L-Final (based on central laboratory results).
• Screening or Visit L-Final laboratory values (based on central laboratory results) of total bilirubin > 2 × the upper limit of normal (ULN) (except if caused by Gilbert's syndrome).
a) ALT > 2 × the ULN
b) AST > 2 × the ULN