Clinical Trial Comparing a Biosimilar Eptacog Alfa With Novoseven, in Patients With Hemophilia With Inhibitors

AryoGen Pharmed Co.48 enrolled

Overview

The purpose of this multicentre, randomized, double-blinded, single dose, two-way cross-over study, is to compare the pharmacokinetics (PK) and pharmacodynamic (PD) of two different doses of the biosimilar eptacog alfa (activated) with Novoseven in 48 patients, adult and children (\>12 years), not bleeding, with hemophilia A or B with inhibitors. Patients will be randomized to receive either a single dose of eptacog alfa biosimilar 90 μg/kg or 270 μg/kg and one single dose of NovoSeven 90 μg/kg or 270 μg/kg, or vice versa, with doses separated by a washout period. All patients will be followed 12 months and will receive biosimilar eptacog alfa, on demand, for every bleeding episode that should occur - or - for prophylaxis, with the aim of monitoring of inhibiting antibody formation, lack of efficacy and collection of safety data.

Forty-eight patients enrolled, not bleeding, will be randomized to receive two injections separated by a washout period of 3 days (t1/2 = 2.3h). Patients are centrally registered and randomized to receive in a 2x2 cross-over setting either a single dose of two for the following products: A: AryoSeven 90 µg/kg and B: NovoSeven 90 µg/kg - or - C: AryoSeven 270 µg/kg and D: NovoSeven 270 µg/kg. Patients will be hospitalized at the time of study medication administration and plasma sampling. Before any treatment, a blood sample will be obtained in all patients for testing for immunogenicity.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hemophilia A or B With Inhibitor

Eligibility

Sex: MALEMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Confirmed diagnosis of congenital hemophilia 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 status * male subjects * adult and children (\>12 years) * 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 the time of study medication administration for plasma sampling (2 times during the study). 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/microliter (at screening visit) * Any clinical sign or known history of an 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 endpoint of the study

Locations (8)

Hemophilia Center - Hematology & Oncology Dept. Shiraz University of Medical Science

Shiraz, Iran

Comprehensive Hemophilia Care Center

Tehran, Iran

Ali Asghar Hospital

Zahedan, Iran

Acibadem Adana Hastanesi, Pediatrik Hematoloji-Onkoloji Bölümü

Adana, Turkey (Türkiye)

Hacettepe Üniversitesi Çocuk Sağlığı ve Hastalıkları Anabilim Dalı Çocuk Hematolojisi Bilim Dalı

Ankara, Turkey (Türkiye)

Uludağ Üniversitesi Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları Anabilim Dalı/Hematoloji Bilim Dalı

Bursa, Turkey (Türkiye)

Istanbul Üniversitesi Cerrahpaşa Tip Fakültesi Çocuk Sağlığı ve Hastalıkları Anabilim Dalı Çocuk Hematoloji-Onkoloji B.D.

Istanbul, Turkey (Türkiye)

Ege Üniversitesi Tip Fakültesi Cocuk Sağliği ve Hastalikari Anabilim Dali ÇocukHematoloji Bilim Dali

Izmir, Turkey (Türkiye)

Outcomes

Primary Outcomes

Area under the plasma concentration time curve from time 0 to infinity, based on the last observed concentration (AUCinf)

Measurement of plasma level of factor VII clotting activity (FVII:C) determined by commercial Staclot® VIIa-recombinant tissue factor assay (Diagnostics Stago, France).