Condition 1: Hemophilia A with inhibitor. Condition 2: Hemophilia B with inhibitor. Deficiency factor VIII (with functional defect) Hereditary factor IX deficiency (with functional defect)
Conditions
Interventions
Intervention 1: AryoGen eptacog alfa (AryoSeven 1.2 mg), intravenous 90 microgram per kg single dose. Lyophilized powder for solution with provided solvent. Intervention 2: AryoGen eptacog alfa (AryoS
Sponsors
AryoGen Pharmed
Eligibility
Sex/Gender
Male
Age
12 Years to No maximum
Inclusion criteria
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, non in bleeding episode -Male subjects -Adult and children (>12 years) -Patients to be enrolled must also provide voluntary written informed consent to the protocol to be eligible for the study. For minor patients, parent/legal guardian will provide consent and, when possible, patient assent will also be obtained. For compromised patients, their designated proxy must provide informed consent. -For the PK/PD phase, patients will be hospitalized at time of study medication administration for plasma sampling (2 times during the study).
Exclusion criteria
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 Novoseven or planned to occur during the trial. -Patients who have received routine (prophylactic) treatment with rFVIIa in the period between screening visit (visit 1) and visit 2 of this study (first dose administration). -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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic parameter: the area under the plasma concentration time curve from time 0 to infinity, based on the last observed concentration (AUCinf). Timepoint: 10 min- prior to dose administration and at 10 min, 20 min, 1 h, 3 h, 5 h, 8 h, 12 h, 24 h and 30 h after AryoSeven or NovoSeven injection. Method of measurement: Measurement of plasma level of factor VII clotting activity (FVII:C) determined by commercial Staclot® VIIa–recombinant tissue factor assay (Diagnostica Stago, Asniéres sur Seine, France)performed by a central lab.;Pharmacodynamic parameters:Thrombin Generation Assay (TGA), D-Dimer, F1.2 prothrombin fragments. Timepoint: Thrombin Generation Assay:10 min prior to dose administration and at 10 min,20 min,1h,3 h,5 h,8 h,12 h,24 h and 30 h after AryoSeven or NovoSeven injection.D-dimer and F1.2 prothrombin fragments- 10 min- prior to dose administration and at 20 min, 1 h, 5 h, and 12 h and 24 h after on the same samples obtained for TGA. Method of measurement: Validated analytical method performed by central lab. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary PK parameters:AUClast, Cmax,tmax, AUCextra;First order rate constant associated with the terminal (log-linear) portion of the curve (?z);Elimination half-life; MRT; CL; Vss. Timepoint: 10 min- prior to dose administration and at 10 min, 20 min, 1 h, 3 h, 5 h, 8 h and 12 h, 24 h and 30 h after AryoSeven or NovoSeven injection. Method of measurement: Pharmacokinetic assessment by measurement of plasma level of factor VII clotting activity (FVII:C) determined by commercial Staclot® VIIa–recombinant tissue factor assay (Diagnostica Stago, Asniéres sur Seine, France)., performed by a central lab.;Clinical parameters in controlling acute bleeding after treatment with AryoSeven. Timepoint: 2 h, 6 h and 12 h post infusion (last AryoSeven dose). Method of measurement: 4 point scale (Excellent, Good, Moderate, None) by the investigator.;Immunogenicity assessment. Timepoint: At screening visit, after the second drug administration (visit 3) and then every 3 months for a year. Method of measurement: PT based Bethesda assay.;Adverse events. Timepoint: at any time during the study. Method of measurement: Adverse events grading for severity, seriousness, expected or unexpected, relationship to the study drug, action taken, outcome. | — |
Countries
Iran (Islamic Republic of)
Contacts
Public ContactAmirhossein Saadatirad
AryoGen Pharmed
Outcome results
None listed