Pivotal Study (Pharmacokinetics, Efficacy, Safety) of BAX 326 (rFIX) in Hemophilia B Patients

• Pharmacokinetic (PK) endpoint [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  The primary PK endpoint is the area under the plasma concentration versus time curve from 0 to 72 hours.
• Hemostatic efficacy [ Time Frame: 48 hours (prophylaxis) ] [ Designated as safety issue: No ]

  Treatment of bleeding episodes: number of infusions per bleeding episode, overall hemostatic efficacy rating at resolution of bleed

  Prophylaxis: annualized bleeding rate

The purpose of this pivotal Phase 1/3 study is to determine the pharmacokinetic (PK) parameters, the hemostatic efficacy, and the safety of BAX 326, a recombinant factor IX, in previously treated patients (PTPs) with severe and moderately severe hemophilia B.

• Biological: BeneFIX and BAX 326 (Recombinant factor IX)

  Parts 1 and 3 (N=27): PK Crossover with BeneFIX (Part 1) / Repeat PK with BAX 326 (Part 3)

  Part 2 (N=75-80): Open-label, uncontrolled, Phase 3: Prophylactic treatment with BAX 326 twice weekly as well as treatment of bleeding episodes (60 subjects) + on-demand treatment (15-20 subjects)

  Other Name: BAX 326
• Biological: BeneFIX (Recombinant factor IX (licensed product))
  Part 1 (PK crossover)
  Other Name: BeneFIX

Main Inclusion Criteria:

• Subject is 12 to 65 years old at the time of screening
• Subject and/or legal representative has/have provided signed informed consent
• Subject has severe (factor IX (FIX) level < 1%) or moderately severe (FIX level 1-2%) hemophilia B (based on the one stage activated partial thromboplastin time [aPTT] assay), as tested at screening at the central laboratory
• Subject is previously treated with plasma-derived or recombinant FIX concentrate(s) for a minimum of 150 exposure days (EDs)(based on the subject's medical records); if a verifiable, documented history is unavailable, the subject can be enrolled if s/he has participated in Study 050901 for at least 50 EDs to Immunine prior to enrollment (not valid for US and Japan).
• Subject has no evidence of a history of FIX inhibitors

Main Exclusion Criteria:

• The subject has a history of FIX inhibitors with a titer >= 0.6 Bethesda Units (BU) (as determined by the Nijmegen modification of the Bethesda assay or the assay employed in the respective local laboratory) at any time prior to screening
• The subject has a detectable FIX inhibitor at screening, with a titer >= 0.6 BU as determined by the Nijmegen modification of the Bethesda assay in the central laboratory
• The subject's weight is < 35 kg or > 120 kg
• The subject has a history of allergic reaction, eg, anaphylaxis, following exposure to FIX concentrate(s)
• The subject has a known hypersensitivity to hamster proteins or rFurin
• The subject has ongoing or recent evidence of a thrombotic disease, fibrinolysis or DIC