Recombinant factor IX Fc fusion protein in children with haemophilia B (Kids B-LONG): results from a multicentre, non-randomised phase 3 study

详细信息    查看全文

• 作者：Kathelijn Fischer ; MD^a ; Roshni Kulkarni ; MD^b ; Beatrice Nolan ; MD^c ; Prof Johnny Mahlangu ; MD^d ; ^e ; Savita Rangarajan ; MD^f ; Giulia Gambino ; MSc^g ; Lei Diao ; PhD^g ; Alejandra Ramirez-Santiago ; MD^g ; Glenn F Pierce ; MD^g ; Dr Geoffrey Allen ; MD^g ; ^{geoff.a.allen@gmail.com}
• 刊名：The Lancet Haematology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：4
• 期：2
• 页码：e75-e82
• 全文大小：810 K
• 卷排序：4

文摘

Kids B-LONG was a multicentre, open-label, phase 3 study assessing the safety, efficacy, and pharmacokinetics of recombinant factor IX Fc fusion protein (rFIXFc) in previously treated paediatric patients younger than 12 years with severe haemophilia B.MethodsThe study enrolled 30 previously treated boys younger than 12 years with haemophilia B (≤2 IU/dL [≤2%] endogenous coagulation factor IX [FIX] activity). All patients were initially given rFIXFc prophylaxis (50–60 IU/kg) once per week with adjustments to dose (≤100 IU/kg per infusion) or dosing frequency (up to two times per week) as needed. The primary outcome measure was development of inhibitors (neutralising antibodies). Secondary outcomes were pharmacokinetics, annual bleeding rate (ABR), spontaneous joint ABR, the number of infusions and dose required to resolve a bleed, time from last infusion of rFIXFc to a bleeding episode, assessment of response to treatment, and total annualised rFIXFc consumption for prevention and treatment of bleeding episodes. All patients underwent sequential pharmacokinetic evaluations of their prestudy FIX and rFIXFc. The completed trial is registered with ClinicalTrials.gov, number NCT01440946.FindingsNo patients developed inhibitors to rFIXFc; in the 30 enrolled patients the most common adverse events were nasopharyngitis (n=7; 23%) and fall (n=6; 20%); four patients (13%) had serious adverse events. Overall, rFIXFc exhibited a prolonged half-life of 68·6 h (95% CI 61·8–76·0), reduced clearance, and similar recovery compared with prestudy FIX. The median ABR was 2·0 (0·0–3·1) overall and 0·0 (0·0–0·0) for spontaneous joint bleeds; ten (33%) of 30 patients reported no bleeding, and 19 (63%) reported no joint bleeding on-study. The median average prophylactic dose of rFIXFc was 58·6 IU/kg (IQR 52·3–64·8) per week. Throughout the study, 29 (97%) of 30 patients remained on once per week infusions.InterpretationWeekly infusions of rFIXFc were well tolerated and resulted in low bleeding rates in children with severe haemophilia B.FundingBiogen, Sobi.