Safety and Pharmacokinetic Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein in Subjects With Hemophilia B

• Frequency of adverse events (AEs) [ Time Frame: up to 14 days after drug administration ] [ Designated as safety issue: Yes ]
• Frequency of serious adverse events (SAEs) [ Time Frame: up to 28 days after drug administration ] [ Designated as safety issue: Yes ]
• Occurrence of inhibitor against FIX [ Time Frame: up to 28 days after drug administration ] [ Designated as safety issue: Yes ]
• Occurrence of antibodies against rIX-FP [ Time Frame: up to 28 days after drug administration ] [ Designated as safety issue: Yes ]

• AUC to the last sample with quantifiable drug concentration (AUC0-t) [ Time Frame: From time of dosing up to 7 days after the dose ] [ Designated as safety issue: No ]
  Following 50 IU/kg rIX-FP infusion
• AUC extrapolated to infinity (AUCt-∞) [ Time Frame: From time of dosing up to 7 days after the dose ] [ Designated as safety issue: No ]
  Following 50 IU/kg rIX-FP infusion
• Half-life (t1/2) [ Time Frame: From time of dosing up to 7 days after the dose ] [ Designated as safety issue: No ]
  Following 50 IU/kg rIX-FP infusion
• Incremental recovery (IU/mL/IU/kg) [ Time Frame: From time of dosing up to 7 days after the dose ] [ Designated as safety issue: No ]
  Defined as FIX activity (IU/mL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion.
• Clearance [ Time Frame: From time of dosing up to 7 days after the dose ] [ Designated as safety issue: No ]
  Following 50 IU/kg rIX-FP infusion

The primary objective of the study is to assess the safety of IV administration of rIX-FP. Safety will be evaluated by adverse events and laboratory changes over time. The secondary objective of the study is to evaluate the pharmacokinetics parameters, following a single intravenous dose of rIX-FP.

This study is comprised of both a rIX-FP dose-escalation safety segment (25, 50 and 75 IU/kg of rIX-FP), and PK evaluation of rIX-FP after a single dose of 50 IU/kg, as well as PK evaluation after a single dose of 50 IU/kg of the previously given Factor IX (FIX) product (recombinant FIX [rFIX] or plasma derived FIX [pdFIX]) which is used as the reference product.

• Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein
  Single dose of 25, 50 or 75 IU/kg of rIX-FP, given as intravenous infusion
• Biological: Plasma derived FIX [pdFIX]
  Single dose of 50 IU/kg of reference product, given as intravenous infusion

• Experimental: Cohort 1
  25 IU/kg dose
  Intervention: Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein
• Experimental: Cohort 2
  50 IU/kg dose
  Interventions:

  • Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein
  • Biological: Plasma derived FIX [pdFIX]
• Experimental: Cohort 3
  75 IU/kg dose
  Intervention: Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein

Inclusion Criteria:

• Male, 12 - 65 years, with body weight ≥ 30 kg and ≤ 120 kg
• Documented severe Hemophilia B (FIX activity of ≤ 2%) or tested by the central laboratory at screening
• Subjects who have received FIX products for > 150 exposure days (EDs) (estimated)
• No confirmed prior history of FIX inhibitor (history of positive FIX inhibitor defined as two consecutive positive tests - a confirmatory test on a second, separately drawn sample shortly after the previous positive test) and confirmed no detectable FIX inhibitors (negative FIX inhibitor defined as < 0.6 Bethesda Units [BU] by the central laboratory at screening
• Subjects can be treated on-demand or under prophylactic therapy
• Signed Informed Consent/Assent

Exclusion Criteria:

• Known hypersensitivity (allergic reaction or anaphylaxis) to any FIX product or hamster protein
• Any known congenital or acquired coagulation disorder other than congenital FIX deficiency
• Platelet count < 100,000/µL
• Immunocompromised (CD4 count < 200/mm3), (HIV positive subjects may participate in the study and protease inhibitors and antiviral therapy are permitted, at the discretion of the Investigator)
• Currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment
• Serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) concentration > 5 times (x) the upper limit of normal (ULN)
• Serum creatinine > 2 x ULN
• Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction and arterial embolus within 3 months prior to enrollment
• Use of an Investigational Medicinal Product (IMP) within 30 days prior to the first rIX-FP administration
• Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months prior to study entry
• Subject currently on a dose and/or regimen of FIX that would preclude participation in the study due to possible increased risk of bleeding because of the requirement to withhold treatment during the PK sampling period
• Suspected inability (e.g., language problem or mental condition) or unwillingness to comply with study procedures or history of noncompliance