CC BY-NC-ND 4.0 · Thromb Haemost 2020; 120(04): 599-606
DOI: 10.1055/s-0040-1705116
Coagulation and Fibrinolysis
Georg Thieme Verlag KG Stuttgart · New York

Long-Term Safety and Efficacy of Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Previously Treated Pediatric Patients with Hemophilia B: Results from a Phase 3b Extension Study

Gili Kenet
1   The Israeli National Hemophilia Center, Sheba Medical Center, Tel Hashomer, Sackler Medical School, Tel Aviv University, Israel
,
Hervé Chambost
2   APHM, Pediatric Hematology Oncology Department, Children Hospital La Timone & Aix Marseille University, INSERM, INRA, C2VN, Marseille, France
,
Christoph Male
3   Department of Pediatrics, Medical University of Vienna, Vienna, Austria
,
Susan Halimeh
4   CRC Coagulation Research Centre GmbH, Duisburg, Germany
,
Thierry Lambert
5   Centre de Traitment des Hémophiles, Hôpital Bicetre, Paris, France
,
Yanyan Li
6   CSL Behring, King of Prussia, United States
,
Wilfried Seifert
7   CSL Behring, Marburg, Germany
,
Elena Santagostino
8   Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
› Author Affiliations
Funding This study was sponsored by CSL Behring.
Further Information

Publication History

10 September 2019

15 January 2020

Publication Date:
17 March 2020 (online)

Abstract

Introduction A phase 3b extension study evaluated the long-term safety and efficacy of a recombinant fusion protein-linking coagulation factor IX (FIX) with albumin (rIX-FP) for the routine prophylaxis and on-demand treatment of bleeding in pediatric hemophilia B patients.

Methods Previously treated patients aged <12 years with moderate to severe hemophilia B enrolled in a 3-year extension study following a phase 3 pivotal study in which they received weekly rIX-FP prophylaxis. In the extension study, they could maintain or extend their prophylaxis interval to every 10 or 14 days if they were well controlled on the 7-day regimen.

Results Compared with their initial regimen, by the end of the study, dosing intervals were the same, extended, and shortened in 16, 4, and 4 patients, respectively. Very low annualized spontaneous bleeding rates (AsBRs) were observed; median AsBR was 0.0 for the 7- and 10-day regimens, and 1.1 for the 14-day regimen. The 7- and 14-day regimens were comparable in preventing spontaneous bleeds; mean (95% confidence interval) difference in AsBR of −1.2 (−2.6 to 0.3) bleeding episodes/year/subject. Overall, 96% of bleeding episodes were successfully treated with one or two injections of rIX-FP. Patients on a 14-day regimen maintained a mean steady-state trough FIX level of >7.2 IU/dL. No patient developed an inhibitor.

Conclusion This extension study demonstrated the long-term safety and efficacy of weekly rIX-FP in pediatric patients. Additionally, it showed that adequate bleed protection can be achieved with 10- or 14-day rIX-FP regimens in selected pediatric patients while maintaining safety.

Note

Editorial support for the writing of this manuscript was provided by Jessica Jackson of Meridian HealthComms in accordance with good publication practice (GPP3) and was funded by CSL Behring. CSL Behring reviewed and provided feedback on the paper. The authors had full editorial control of the paper and provided their final approval of all content.


Members of the PROLONG-9FP Investigators Study Group

Australia: Christopher Barnes, Royal Children's Hospital, Victoria; Julie Curtin, The Children's Hospital Westmead, NSW; Canada: Anthony Chan, McMaster Children's Hospital, Hamilton, ON; Czech Republic: Jan Blatny, Children's University Hospital, Masaryk University, Brno; Bohumir Blazek, University Hospital Ostrava, Ostrava-Poruba; Vladimir Komrska, University Hospital Motol, Prague; Germany: Hans-Jürgen Laws, Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich-Heine Universitaet, Dusseldorf; Spain: Maria-Teresa Álvarez Román, Hospital Universitario La Paz, Madrid.