Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children

Gili Kenet; Hervé Chambost; Christoph Male; Thierry Lambert; Susan Halimeh; Tatiana Chernova; Maria Elisa Mancuso; Julie Curtin; Christine Voigt; Yanyan Li; Iris Jacobs; Elena Santagostino; the PROLONG-9FP Investigator Study Group

doi:10.1160/TH16-03-0179

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2016; 116(04): 659-668
DOI: 10.1160/TH16-03-0179

Coagulation and Fibrinolysis

Schattauer GmbH

Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children

Results of a phase 3 trial

Gili Kenet

¹The Israeli National Hemophilia Center, Sheba Medical Center, Tel Hashomer, Sackler Medical School, Tel Aviv University, Israel

,

Hervé Chambost

²Pediatric Hematology Oncology Department, Children Hospital La Timone, APHM, Aix Marseille University, Marseille, France

,

Christoph Male

³Department of Pediatrics, Medical University of Vienna, Vienna, Austria

,

Thierry Lambert

⁴Centre de Traitement des ‘Hemophilies, Hopital Bicetre, Paris, France

,

Susan Halimeh

⁵CRC Coagulation Research Centre GmbH, Duisburg, Germany

,

Tatiana Chernova

⁶Kirov Research Institute of Hematology and Blood Transfusion, Kirov, Russia

,

Maria Elisa Mancuso

⁷Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

,

Julie Curtin

⁸Children’s Hospital at Westmead, Sydney Children’s Hospital Network, Sydney, Australia

⁹Discipline of Paediatrics and Child Health, University of Sydney, Australia

,

Christine Voigt

¹⁰CSL Behring, CRD, King of Prussia, Pennsylvania, USA

,

Yanyan Li

¹⁰CSL Behring, CRD, King of Prussia, Pennsylvania, USA

,

Iris Jacobs

¹⁰CSL Behring, CRD, King of Prussia, Pennsylvania, USA

,

Elena Santagostino

⁷Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

,

the PROLONG-9FP Investigator Study Group

› Institutsangaben

Abstract

Summary

A global phase 3 study evaluated the pharmacokinetics, efficacy and safety of a recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 27 previously treated male children (1–11 years) with severe and moderately severe haemophilia B (factor IX [FIX] activity ≤2 IU/dl). All patients received routine prophylaxis once every seven days for up to 77 weeks, and treated any bleeding episodes on-demand. The mean terminal half-life of rIX-FP was 91.4 hours (h), 4.3-fold longer than previous FIX treatment and clearance was 1.11 ml/h/kg, 6.4-fold slower than previous FIX treatment. The median (Q1, Q3) annualised spontaneous bleeding rate was 0.00 (0.00, 0.91) and was similar between the <6 years and ≥6 years age groups, with a weekly median prophylactic dose of 46 IU/kg. In addition, patients maintained a median trough level of 13.4 IU/dl FIX activity on weekly prophylaxis. Overall, 97.2 % of bleeding episodes were successfully treated with one or two injections of rIX-FP (95 % CI: 92 % to 99 %), 88.7 % with one injection, and 96 % of the treatments were rated effective (excellent or good) by the Investigator. No patient developed FIX inhibitors and no safety concerns were identified. These results indicate that rIX-FP is safe and effective for preventing and treating bleeding episodes in children with haemophilia B with weekly prophylaxis. Routine prophylaxis with rIX-FP at treatment intervals of up to 14 days are currently being investigated in children with severe and moderately severe haemophilia B. Clinicaltrials.gov (NCT01662531)

Keywords

Haemophilia B - factor IX - on-demand treatment - prophylactic regimen - rIX-FP

Volltext

Referenzen

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