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

Recruitment & Eligibility

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

Study & Design

Arm && Interventions

Group	Intervention	Description
Cohort 1	Recombinant Coagulation Factor IX Albumin Fusion Protein	25 IU/kg dose
Cohort 2	Recombinant Coagulation Factor IX Albumin Fusion Protein	50 IU/kg dose
Cohort 2	Plasma derived FIX [pdFIX]	50 IU/kg dose
Cohort 3	Recombinant Coagulation Factor IX Albumin Fusion Protein	75 IU/kg dose

Primary Outcome Measures

Name	Time	Method
Occurrence of inhibitor against FIX	up to 28 days after drug administration
Occurrence of antibodies against rIX-FP	up to 28 days after drug administration
Frequency of adverse events (AEs)	up to 14 days after drug administration
Frequency of serious adverse events (SAEs)	up to 28 days after drug administration

Secondary Outcome Measures

Name	Time	Method
AUC to the last sample with quantifiable drug concentration (AUC0-t)	From time of dosing up to 7 days after the dose	Following 50 IU/kg rIX-FP infusion
AUC extrapolated to infinity (AUCt-∞)	From time of dosing up to 7 days after the dose	Following 50 IU/kg rIX-FP infusion
Half-life (t1/2)	From time of dosing up to 7 days after the dose	Following 50 IU/kg rIX-FP infusion
Incremental recovery (IU/mL/IU/kg)	From time of dosing up to 7 days after the dose	Defined as FIX activity (IU/mL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion.
Clearance	From time of dosing up to 7 days after the dose	Following 50 IU/kg rIX-FP infusion

Recruitment & Eligibility