]>
IRCT20161202031193N3 IRCT 2021-02-01 AryoGen Pharmed The Study of Dose Response Relationship Evaluation of AryoSeven in Hemophilia Patients UGA 2020-01 An Exploratory Study to Evaluate the Dose Response Relationship of Pharmacodynamic Parameters of Aryoseven in Patients with Hemophilia A and B with Inhibitors 2020-12-29 anticipated 12 Complete https://irct.ir/trial/53611 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Not used, Assignment: Crossover, Purpose: Other, Other design features: An exploratory study to evaluate dose-response relationship of PD markers as surrogate efficacy endpoints, Randomization description: Randomization will be performed using a randomization list prepared by an independent statisticians. The patient will be assigned to a specific treatment sequence. Possible sequence are planned on a balanced Latin Square design in 1:1 manner using Interactive Web Response System (IWRS), Blinding description: Blinding will be performed by an independent third-party operator (nurse/pharmacist, unblinded), who will prepare undistinguishable syringes with patient’s dosing and labelling. All people involved in the study are blind except the nurse or pharmacist who is responsible of preparing patient's treatment and an unblind CRA who is responsible for monitoring the blinding procedure. 2 Condition 1: Congenital Hemophilia A with inhibitors. Condition 2: Congenital Hemophilia B with inhibitors. 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 lyophilized powder provided)/ Product of AryoGen Pharmed. Intervention 2: Intervention group: Single dose Infusion of Biosimilar Eptacog alpha, activated (AryoSeven) 30 ug/kg in the arm that blood sampling has not taken place (after reconstitution of lyophilized powder provided)/ Product of AryoGen Pharmed. Intervention 3: Intervention group: Single dose Infusion of Biosimilar Eptacog alpha, activated (AryoSeven) 90 ug/kg in the arm that blood sampling has not taken place (after reconstitution of lyophilized powder provided)/ Product of AryoGen Pharmed. Intervention 4: Intervention group: Single dose Infusion of Biosimilar Eptacog alpha, activated (AryoSeven) 270 ug/kg in the arm that blood sampling has not taken place (after reconstitution of lyophilized powder provided)/ Product of AryoGen Pharmed. Intervention 5: Control group: Single dose Infusion of Eptacog alpha, activated (NovoSeven) 30 ug/kg in the arm that blood sampling has not taken place (after reconstitution of lyophilized powder provided)/ Product of Novo Nordisk. 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 No other information is available
public Amirhossein Saadatirad
No. 140, Cross Tajbakhsh st, 24th Km Tehran Karaj Makhsous road
Tehran Iran (Islamic Republic of) 3164819711 +98 26 3610 6480 saadatirada@aryogen.com AryoGen Pharmed scientific Dr. Hasan Abolghasemi
Nosrati st, Mollasadra str, south Sheykh Bahaii str, Tehran
Tehran Iran (Islamic Republic of) 8174673461 +98 21 8248 3131 h.abolghasemi.ha@gmail.com Bagheiat-allah University of Medical Sciences Iran (Islamic Republic of) 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). 12 years no limit Male 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. D66 D67 Hereditary factor VIII deficiency Hereditary factor IX deficiency Treatment - Drugs Treatment - Drugs Treatment - Drugs Treatment - Drugs Treatment - Drugs 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 lyophilized powder provided)/ Product of AryoGen Pharmed Intervention group: Single dose Infusion of Biosimilar Eptacog alpha, activated (AryoSeven) 30 ug/kg in the arm that blood sampling has not taken place (after reconstitution of lyophilized powder provided)/ Product of AryoGen Pharmed Intervention group: Single dose Infusion of Biosimilar Eptacog alpha, activated (AryoSeven) 90 ug/kg in the arm that blood sampling has not taken place (after reconstitution of lyophilized powder provided)/ Product of AryoGen Pharmed Intervention group: Single dose Infusion of Biosimilar Eptacog alpha, activated (AryoSeven) 270 ug/kg in the arm that blood sampling has not taken place (after reconstitution of lyophilized powder provided)/ Product of AryoGen Pharmed Control group: Single dose Infusion of Eptacog alpha, activated (NovoSeven) 30 ug/kg in the arm that blood sampling has not taken place (after reconstitution of lyophilized powder provided)/ Product of Novo Nordisk 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. 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). AryoGen Pharmed Approved 2020-12-09 Baqiyatallah University of Medical Sciences Shahid Nosrati st, South Sheykh Bahaee st, Mollasadra st, Vanak sq, Tehran Tehran Iran (Islamic Republic of)