Descarga: Recombinant FXIII (rFXIII-A 2 ) Prophylaxis Prevents Bleeding and Allows for Surgery in Patients with Congenital FXIII A-Subunit Deficiency
Archivo: ehh/T Hemost 2018 Carcao recombinant FXIII.pdf
Recombinant factor XIII-A 2 (rFXIII-A 2 ) was developed for prophylaxis and treatment of bleeds in patients with congenital FXIII A-subunit de fi ciency. mentor ™ 2 (NCT00978380), a multi- national, open-label, single-arm, multiple-dosing extension to the pivotal mentor ™ 1trial, assessed long-term safety and ef fi cacy of rFXIII-A 2 prophylaxis in eligible patients (patients with severe [ < 0.05 IU/mL] congenital FXIII subunit A de fi ciency) aged 6 years. Patients received35IU/kgrFXIII-A 2 (exactdosing)every28 2daysfor 52weeks.Primaryendpoint was safety (adverse events including immunogenicity); secondary endpoints were rate of bleeds requiring FXIII treatment, haemostatic response after one 35 IU/kg rFXIII-A 2 dose for breakthrough bleeds and withdrawals due to lack of rFXIII-A 2 ef fi cacy. Steady-state pharmacokinetic variables were also summarized. Elective surgery was permitted during the treatment period. Sixty patients were exposed to rFXIII-A 2 ;theirmedianagewas 26.0 years (range: 7.0 – 77.0). rFXIII-A 2 was well tolerated without any safety concerns. No non-neutralizing or neutralizing antibodies (inhibitors) against FXIII were detected. Mean annualized bleeding rate (ABR) was 0.043/patient-year. Mean spontaneous ABR was 0.011/patient-year. No patients withdrew due to lack of ef fi cacy. Geometric mean FXIII trough level was 0.17 IU/mL. Geometric terminal half-life was 13.7 days. rFXIII-A 2 prophylaxis provided suf fi cient haemostatic coverage for 12 minor surgeries without the need for additional FXIII therapy; eight procedures were performed within 7 days of the patient ’ slast scheduled rFXIII-A 2 dose, and four were performed 10 to 21 days after the last dose.
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