Hemophilia A With Inhibitor, Hemophilia B With Inhibitor
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALEptacog alfa, activated
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.
Sponsors
AryoGen Pharmed Co.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of congenital haemophilia A or B with inhibitors to FVIII or FIX titer \>5 Bethesda Units \[BU\] * with \> 2 episodes of bleeding/year requiring treatment with FVII infusions, not in bleeding episode * Male adults and adolescents (\>12 years) * Patient informed consent has been obtained \[Patients to be enrolled must also provide voluntary written informed consent to the protocol prior to screening to be eligible for the study. For adolescents, parent/legal guardian must provide consent and, wherever possible, patient assent will also be obtained. For compromised patients, their designated proxy must provide informed consent\]. * Patients willing and able to be hospitalized prior to time of study medication administration for plasma sampling (5 times during the study).
Exclusion criteria
* Any other type of congenital or acquired coagulopathy, such as: liver disease (hepatitis), vitamin k deficiency, uremia, malignancy. * Antibodies against Factor VII * Ongoing bleeding prophylaxis regimens with AryoSeven/NovoSeven or planned to occur during the trial * Platelet count less than 100.000 platelets/mcL (at screening visit) * Any clinical sign or known history of arterial thrombotic event or deep venous- thrombosis or pulmonary embolism * HIV positive with current CD4+ count of less than 200/µL * Liver cirrhosis * Factor VIII/IX immune tolerance induction regimen planned to occur during the trial * Known hypersensitivity to the study medication * Parallel participation in another experimental drug trial. * Parallel participation in another marketed drug trial that may affect the primary end-point of the study. * Concomitant diseases and/or medications, or any other conditions, that render the patient unsuitable for inclusion into the study in the judgement of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lag time of the thrombin generation curve | Up to 30 hours after AryoSeven and NovoSeven injection | Time to 16.7% of peak plasmatic concentration, in minutes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax (PK parameter) | Up to 30 hours after AryoSeven and NovoSeven injection | Observed maximum plasma concentration |
| Time of Cmax (PK parameter) | Up to 30 hours after AryoSeven and NovoSeven injection | Time of observed maximum plasma concentration |
| Endogenous Thrombin Potential (PD parameter) | Up to 30 hours after AryoSeven and NovoSeven injection | Area under the curve plasma levels of thrombin generation curve (in nmol/per minute) |
| Time to Peak (PD parameter) | Up to 30 hours after AryoSeven and NovoSeven injection | Time to Peak of thrombin generation curve (in minutes) |
| Peak height (PD parameter) | Up to 30 hours after AryoSeven and NovoSeven injection | Peak height of thrombin generation curve (in nmol/ml) |
| F1.2 prothrombin fragments (PD parameter) | Up to 30 hours after AryoSeven and NovoSeven injection | Peak height (micg/L) |
| D-dimer (PD parameter) | Up to 30 hours after AryoSeven and NovoSeven injection | Peak height (micg/L) |
| AUCinf (PK parameter) | Up to 30 hours after AryoSeven and NovoSeven injection | Area under the plasma concentration time curve from time 0 to infinity, based on the last observed concentration; |
Countries
Iran
Outcome results
None listed