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IRCT2016120231193N1 IRCT 2016-12-25 AryoGen Pharmed The pharmacokinetic study of AryoSeven with Novoseven in Patients with Congenital Factor VII Deficiency A Randomized, Multi-center, Single Dose, Cross over Study Comparing the Pharmacokinetic of Bio-similar EPTACOG Alfa with NOVOSEVEN®, in Patients with Congenital Factor VII Deficiency 2016-12-21 anticipated 24 Complete https://irct.ir/trial/24586 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Not used, Assignment: Crossover, Purpose: Treatment, Randomization description: The eligible patients are administered randomly in a 1:1 manner with either AryoSeven or NovoSeven. Allocation of treatment in this study is performed randomly using block randomization. Randomization sequence is prepared using R-CAN software version 4.0.1 in a blocks of 2 or 4 for 24 patients. Randomization list is prepared by an independent statisticians based on a balanced Latin Square design and the code is allocated to a patient by a third party in the study site based on the order of enrollment, Blinding description: Blinding is performed by an independent third party operator (nurse/pharmacist, unblinded), who will prepared undistinguishable syringes with patient’s dosing and labelling. 3 Hereditary deficiency of factor VII. 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 dose of 30 mcg per kg. Undecided - It is not yet known if there will be a plan to make this available Justification or reason for indecision in sharing IPD is not yet decided
public Amirhossein Saadatirad
No 140, corner of Tajbakhsh street, 24th Km of Tehran Karaj Makhsous road
Garmdareh Iran (Islamic Republic of) 3164819712 +98 26 3610 6480 saadatirada@aryogen.com AryoGen Pharmed scientific Dr. Hasan Abolghasemi
Baqiatallah hospital clinic, Mollasadra st, south Sheykh Bahaii st, Tehran, Iran
Tehran Iran (Islamic Republic of) 1435915371 0098218882742 Abolghasem@bmsu.ac.ir Baqiyatallah Hospital Iran (Islamic Republic of) Iran (Islamic Republic of) Patients with a confirmed diagnosis of congenital, severe Factor VII deficiency (FVII <1%), with >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). 12 years 99 years Both 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. D68.2 Hereditary deficiency of other clotting factors Treatment - Drugs Treatment - Drugs Biosimilar eptacog alfa (AryoSeven) product of AryoGen Pharmed, intravenous, single dose of 30 mcg per kg Novo Nordisk eptacog alfa (Novoseven), intravenous, single dose of 30 mcg per kg 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 Pharmacokinetic parameters: AUCinf, Vd, Thalf, Tmax, Clearance, Mean Residence Time, λz. 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. NCT03079063 clinicaltrials.gov AryoGen Pharmed Approved 2016-09-25 Iran University of Medical science Iran University of Medical Sciences ,Shahid Hemmat Highway Tehran Tehran Iran (Islamic Republic of) Approved 2016-12-14 Added at 2017-01-07: Shiraz University of Medical Sciences Added at 2017-01-07: Shiraz University of Medical Sciences Added at 2017-01-07: Shiraz Fars Iran (Islamic Republic of)