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

An Open-label, Multicenter, Dose-Escalation Safety and Pharmacokinetic Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Subjects With Hemophilia B

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.

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