HAEMOPHILIA A OR B WITH INHIBITORS MedDRA version: 20.0 Level: LLT Classification code 10053752 Term: Hemophilia B with anti factor IX System Organ Class: 100000004850 MedDRA version: 20.0 Level: LLT Classification code 10053751 Term: Hemophilia A with anti factor VIII System Organ Class: 100000004850
Conditions
Interventions
Product Name: AryoSeven
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: EPTACOG ALFA (ACTIVATED)
CAS Number: 102786-61-8
Concentration unit: µg/kg microgram(s)/
Sponsors
Aryogen Pharmed
Eligibility
Sex/Gender
Male
Inclusion criteria
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). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 48 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 |
|---|---|
| Main Objective: To demonstrate bioequivalence of biosimilar Eptacog alfa compared with NovoSeven based on primary pharmacokinetic and pharmacodynamic parameters.;Secondary Objective: ? To demonstrate similar pharmacokinetic profile of the biosimilar eptacog alfa AryoSeven and NovoSeven with regards to other PK parameters. ? Clinical response in controlling acute bleeding. and safety: - to evaluate immunogenicity of biosimilar eptacog alfa (formation of neutralizing antibodies) - adverse events;Primary end point(s): Primary Parameters: • Primary PK-parameters: the area under the plasma concentration time curve from time 0 to infinity, based on the last observed concentration (AUCinf) • Pharmacodynamic parameters: Treatment response to Thrombin Generation Assay (TGA), D-Dimer, F1.2 prothrombin fragments;Timepoint(s) of evaluation of this end point: 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 for D-dimer and F 1.2: 10 min- prior to dose administration and at 20 min, 1 h, 5 h, 12 h and 24 h after | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Pharmacokinetic parameters include comparison of: • Area under the plasma concentration-time curve from 0 to the last measurable time point tlast (AUClast) • Observed maximum plasma concentration (Cmax) • Time of Cmax (tmax); • Fraction of the total AUCinf that was derived by extrapolation beyond tlast (AUCextra); • First order rate constant associated with the terminal (log-linear) portion of the curve (?z); • Elimination half-life; calculated as ln(2)/?z (t½); • Mean residence time (MRT); • Clearance and CL/Dose (CL); • Volume of distribution (Vss) AUCinf, AUClast, Cmax and CL will also be evaluated dose normalized as secondary PK parameters (AUClast-norm, AUCinf-norm, Cmax-norm, Cl-norm). This will be done for each patient by dividing the respective parameter though the individual dose given.;Timepoint(s) of evaluation of this end point: 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 | — |
Countries
Belarus, Bulgaria, Iran, Islamic Republic of, Serbia, Turkey
Contacts
Public ContactAmirhossein Saadatirad
Aryogen Pharmed
Outcome results
None listed