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DOI: 10.1055/s-0038-1624581
Recombinant FXIII (rFXIII-A2) Prophylaxis Prevents Bleeding and Allows for Surgery in Patients with Congenital FXIII A-Subunit Deficiency
Publication History
21 September 2017
11 December 2017
Publication Date:
15 February 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201803/lookinside/thumbnails/10-1055-s-0038-1624581_170655-1.jpg)
Abstract
Recombinant factor XIII-A2 (rFXIII-A2) was developed for prophylaxis and treatment of bleeds in patients with congenital FXIII A-subunit deficiency. mentor™2 (NCT00978380), a multinational, open-label, single-arm, multiple-dosing extension to the pivotal mentor™1 trial, assessed long-term safety and efficacy of rFXIII-A2 prophylaxis in eligible patients (patients with severe [<0.05 IU/mL] congenital FXIII subunit A deficiency) aged ≥6 years. Patients received 35 IU/kg rFXIII-A2 (exact dosing) every 28 ± 2 days for ≥52 weeks. Primary endpoint was safety (adverse events including immunogenicity); secondary endpoints were rate of bleeds requiring FXIII treatment, haemostatic response after one 35 IU/kg rFXIII-A2 dose for breakthrough bleeds and withdrawals due to lack of rFXIII-A2 efficacy. Steady-state pharmacokinetic variables were also summarized. Elective surgery was permitted during the treatment period. Sixty patients were exposed to rFXIII-A2; their median age was 26.0 years (range: 7.0–77.0). rFXIII-A2 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 efficacy. Geometric mean FXIII trough level was 0.17 IU/mL. Geometric terminal half-life was 13.7 days. rFXIII-A2 prophylaxis provided sufficient haemostatic coverage for 12 minor surgeries without the need for additional FXIII therapy; eight procedures were performed within 7 days of the patient's last scheduled rFXIII-A2 dose, and four were performed 10 to 21 days after the last dose.
Financial Support
This trial was sponsored by Novo Nordisk A/S (Bagsværd, Denmark).
Author Contributions
M.-L. Garly and A. Rosholm: representing Novo Nordisk A/S study concept and protocol. A. Rosholm: statistical analyses. M. Carcao, C. Altisent, G. Castaman, K. Fukutake, B. Kerlin, C. Kessler, R. Lassila, D. Nugent, J. Oldenburg and A. Inbal: data acquisition. M. Carcao, C. Altisent, G. Castaman, K. Fukutake, B. Kerlin, C. Kessler, R. Lassila, D. Nugent, J. Oldenburg, M.-L. Garly, A. Rosholm and A. Inbal: analysis and interpretation of data. M. Carcao: manuscript drafting. M. Carcao, C. Altisent, G. Castaman, K. Fukutake, B. Kerlin, C. Kessler, R. Lassila, D. Nugent, J. Oldenburg, M.-L. Garly, A. Rosholm and A. Inbal: critical revision and final draft of manuscript.
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