Condition 1: Congenital Hemophilia A with inhibitors. Condition 2: Congenital Hemophilia B with inhibitors. Hereditary factor VIII deficiency Hereditary factor IX deficiency
Conditions
Interventions
Intervention 1: Intervention group: Single dose Infusion of Biosimilar Eptacog alpha, activated (AryoSeven) 10 ug/kg in the arm that blood sampling has not taken place (after reconstitution of lyophil
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 adult and adolescents (>12 years) Patients 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
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 judgment of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Pharmacodynamic Parameter: TGA. 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: Thrombin Generation will be measured using the ST-Genesia® Thrombin Generation System (Diagnostica Stago, Asniéres sur Seine, France). Genesia® is a fully automated TG analyzer. In comparison to the CAT assay, ST Genesia® provides a normalization of each TG parameter based on a reference plasma for each test aiming to reduce the interlaboratory variability as well as the variability between differed measurement runs. | — |
Secondary
| Measure | Time frame |
|---|---|
| PD Parameters: D-Dimer, F1.2. Timepoint: 10 min prior to dose administration and at 20 min, 1 h, 5 h, and 12 h and 24 h after. Method of measurement: Validated analytical method performed by central lab.;Measurement of plasma level of factor VII clotting activity (FVII:C). 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: Pharmacokinetic assessment of plasma level of factor VII clotting activity. (FVII:C) will be determined by commercial Staclot® VIIa–recombinant tissue factor assay (Diagnostica Stago, Asniéres sur Seine, France). | — |
Countries
Iran (Islamic Republic of)
Contacts
Public ContactAmirhossein Saadatirad
AryoGen Pharmed
Outcome results
None listed