Hemophilia B
Conditions
Brief summary
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
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.
Interventions
Single dose of 25, 50 or 75 IU/kg of rIX-FP, given as intravenous infusion
BIOLOGICALPlasma derived FIX [pdFIX]
Single dose of 50 IU/kg of reference product, given as intravenous infusion
Sponsors
CSL Behring
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Clearance | 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. |
Countries
Austria, France, Germany, Israel, Italy, Spain
Outcome results
None listed