Hereditary deficiency of factor VII. Hereditary deficiency of other clotting factors
Conditions
Interventions
Intervention 1: Biosimilar eptacog alfa (AryoSeven) product of AryoGen Pharmed, intravenous, single dose of 30 mcg per kg. Intervention 2: Novo Nordisk eptacog alfa (Novoseven), intravenous, single do
Sponsors
AryoGen Pharmed
Eligibility
Sex/Gender
All
Age
12 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patients with a confirmed diagnosis of congenital, severe Factor VII deficiency (FVII 2 episodes of bleeding/year requiring treatment with FVII infusions, in non-bleeding status. Male and female 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. Patients in the Pharmacokinetic (PK) phase will be hospitalized at time of study medication administration and plasma sampling (2 times during the study).
Exclusion criteria
Exclusion criteria: Any other type of congenital or acquired coagulopathy (except congenital Factor VII deficiency), such as: liver disease (hepatitis), vitamin k deficiency, uremia, malignancy. Antibodies against Factor VII Patients entering the PK Phase who have not suspended prophylactic regime with Novoseven or AryoSeven 3 days before starting the trial (receiving first dose of study medication). Platelet count less than 100.000 platelets/mcL (at screening visit) 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) 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 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 |
|---|---|
| PK-parameters: the area under the plasma activity-time curve from time 0 to last quantifiable activity (AUClast). Timepoint: 10 min before drug administration,10 min, 20 min, 1 h, 3 h, 6 h, 8 h and 12 h and 24 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 blinded to the patient’s treatment.;PK-parameters: maximum plasma activity Cmax. Timepoint: 10 min before drug administration,10 min, 20 min, 1 h, 3 h, 6 h, 8 h and 12 h and 24 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 blinded to the patient’s treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Pharmacokinetic parameters: AUCinf, Vd, Thalf, Tmax, Clearance, Mean Residence Time, ?z. Timepoint: For secondary PK parameters:10 min before drug administration,10 min, 20 min, 1 h, 3 h, 6 h, 8 h and 12 h and 24 h after AryoSeven or NovoSeven injection. Method of measurement: PK Parameters: Measurement of plasma level of factor VII clotting activity (FVII:C) performed by a central lab.;Immunogenicity assessment. Timepoint: At screening visit, after the second dose/second drug administration (visit 3) and then every 3 months for a year. Method of measurement: Immunogenicity by PT-based bethesda assay by local lab and confirmatory test by the modified Nijmegen method of the Bethesda assay by central lab.;Clinical response in treatment of bleeding. Timepoint: 2h , 6h and 12 h after last dose of Aryoseven injection at every bleeding. Method of measurement: 4 point scale (Excellent, Good, Moderate, None) by investigator.;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