TY - JOUR
T1 - Recombinant factor IX Fc fusion protein in children with haemophilia B (Kids B-LONG)
T2 - results from a multicentre, non-randomised phase 3 study
AU - Fischer, Kathelijn
AU - Kulkarni, Roshni
AU - Nolan, Beatrice
AU - Mahlangu, Johnny
AU - Rangarajan, Savita
AU - Gambino, Giulia
AU - Diao, Lei
AU - Ramirez-Santiago, Alejandra
AU - Pierce, Glenn F.
AU - Allen, Geoffrey
N1 - Copyright © 2017 Elsevier Ltd. All rights reserved.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Background 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. Methods The 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. Findings No 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. Interpretation Weekly infusions of rFIXFc were well tolerated and resulted in low bleeding rates in children with severe haemophilia B. Funding Biogen, Sobi.
AB - Background 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. Methods The 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. Findings No 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. Interpretation Weekly infusions of rFIXFc were well tolerated and resulted in low bleeding rates in children with severe haemophilia B. Funding Biogen, Sobi.
UR - http://www.scopus.com/inward/record.url?scp=85011116061&partnerID=8YFLogxK
U2 - 10.1016/S2352-3026(16)30193-4
DO - 10.1016/S2352-3026(16)30193-4
M3 - Article
C2 - 28159192
AN - SCOPUS:85011116061
SN - 2352-3026
VL - 4
SP - e75-e82
JO - Lancet haematology
JF - Lancet haematology
IS - 2
ER -