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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Hemophilia B

Intervention / Treatment
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* Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein
* Biological: Plasma derived FIX [pdFIX]


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>25 IU/kg dose | Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein<br>* Single dose of 25, 50 or 75 IU/kg of rIX-FP, given as intravenous infusion<br>|
| Experimental: Cohort 2<br>50 IU/kg dose | Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein<br>* Single dose of 25, 50 or 75 IU/kg of rIX-FP, given as intravenous infusion<br>Biological: Plasma derived FIX [pdFIX]<br>* Single dose of 50 IU/kg of reference product, given as intravenous infusion<br>|
| Experimental: Cohort 3<br>75 IU/kg dose | Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein<br>* Single dose of 25, 50 or 75 IU/kg of rIX-FP, given as intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

Secondary Outcome Measures

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