Randomized, double-blind, single-dose, 5 ways crossover, exploratory clinical trial evaluating four different doses of AryoSeven (eptacog alfa, activated) and NovoSeven on selected pharmacodynamic parameters in patients with hemophilia with inhibitors.
Randomized, double-blind, single dose, 5 ways crossover, clinical trial evaluating four different doses (10 µg/kg, 30 µg/kg, 90 µg/kg, and 270 µg/kg) of AryoSeven (recombinant human FVII activated or eptacog alfa, activated) and one dose of NovoSeven (30 µg/kg) on selected pharmacodynamic parameters (PD) \[Primary: Thrombin Generation Assay (TGA)\] in male adult and adolescent (\>12 years) patients with hemophilia A or B, with an inhibitors titer \>5 Bethesda Units \[BU\] and not in bleeding status. This will be an exploratory study to evaluate dose-response relationship of PD markers as surrogate efficacy endpoints.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
14
A dose sequence for each injection will be randomly selected from the following doses: 10 μg/kg, 30 μg/kg, 90 μg/kg, or 270 μg/kg, separated by a wash-out period of 3 days.
Comprehensive Hemophilia Care Center
Tehran, Iran
Lag time of the thrombin generation curve
Time to 16.7% of peak plasmatic concentration, in minutes.
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
Endogenous Thrombin Potential (PD parameter)
Area under the curve plasma levels of thrombin generation curve (in nmol/per minute)
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
Time to Peak (PD parameter)
Time to Peak of thrombin generation curve (in minutes)
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
Peak height (PD parameter)
Peak height of thrombin generation curve (in nmol/ml)
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
F1.2 prothrombin fragments (PD parameter)
Peak height (micg/L)
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
D-dimer (PD parameter)
Peak height (micg/L)
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
AUCinf (PK parameter)
Area under the plasma concentration time curve from time 0 to infinity, based on the last observed concentration;
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
Cmax (PK parameter)
Observed maximum plasma concentration
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Time frame: Up to 30 hours after AryoSeven and NovoSeven injection
Time of Cmax (PK parameter)
Time of observed maximum plasma concentration
Time frame: Up to 30 hours after AryoSeven and NovoSeven injection