Young Guy, Collins Peter W, Colberg Torben, Chuansumrit Ampaiwan, Hanabusa Hideji, Lentz Steven R, Mahlangu Johnny, Mauser-Bunschoten Evelien P, Négrier Claude, Oldenburg Johannes, Patiroglu Turkan, Santagostino Elena, Tehranchi Ramin, Zak Marek, Karim Faraizah Abdul
Hemostasis and Thrombosis Center, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, United States.
Arthur Bloom Haemophilia Centre, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Thromb Res. 2016 May;141:69-76. doi: 10.1016/j.thromres.2016.02.030. Epub 2016 Mar 2.
Paradigm™4 was an international extension trial investigating the safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in haemophilia B patients (FIX activity ≤2%; aged 13-70years) who had previously participated in phase III pivotal (paradigm™2) or surgery (paradigm™3) trials.
Patients chose to continue treatment with nonacog beta pegol in either one of two once-weekly prophylaxis arms (10IU/kg or 40IU/kg), or an on-demand arm (40IU/kg for mild/moderate bleeds; 80IU/kg for severe bleeds). The primary objective was to evaluate immunogenicity; key secondary objectives included assessing safety and haemostatic efficacy in the treatment and prevention of bleeds.
Seventy-one patients received prophylaxis or on-demand treatment. No patient developed an inhibitor and no safety concerns were identified. The success rate for the treatment of reported bleeds was 94.6%; most (87.9%) resolved with one injection. The median annualised bleeding rate for patients on prophylaxis was 1.36 (interquartile range [IQR] 0.00-2.23) and 1.00 (IQR 0.00-2.03) for the 10 and 40IU/kg treatment arms, respectively. The mean FIX activity trough achieved for 10 and 40IU once weekly was 9.8% and 21.3%, respectively. Fourteen patients on prophylaxis underwent 23 minor surgical procedures; haemostatic perioperative outcomes for all of those evaluated were 'excellent' or 'good'.
Nonacog beta pegol showed a favourable tolerability profile (with no safety issues identified) with good prophylactic protection and control of bleeding in previously treated adult and adolescent haemophilia B patients.
Paradigm™4是一项国际扩展试验，旨在研究非阿糖苷β聚乙二醇（一种半衰期延长的重组糖基化聚乙二醇化因子IX（FIX））在曾参与III期关键试验（Paradigm™2）或手术试验（Paradigm™3）的B型血友病患者（FIX活性≤2%；年龄13 - 70岁）中的安全性和有效性。
患者选择在两个每周一次的预防治疗组（10IU/kg或40IU/kg）之一或按需治疗组（轻度/中度出血时40IU/kg；重度出血时80IU/kg）中继续接受非阿糖苷β聚乙二醇治疗。主要目标是评估免疫原性；关键次要目标包括评估治疗和预防出血时的安全性和止血效果。
71例患者接受了预防治疗或按需治疗。没有患者产生抑制剂，也未发现安全问题。报告出血的治疗成功率为94.6%；大多数（87.9%）经一次注射后出血停止。预防治疗患者的年化出血率中位数在10IU/kg和40IU/kg治疗组分别为1.36（四分位间距[IQR] 0.00 - 2.23）和1.00（IQR 0.00 - 2.03）。每周一次10IU和40IU治疗达到的平均FIX活性谷值分别为9.8%和21.3%。14例接受预防治疗的患者进行了23次小手术；所有接受评估患者的围手术期止血结果均为“优秀”或“良好”。
非阿糖苷β聚乙二醇显示出良好的耐受性（未发现安全问题），对先前接受治疗的成年和青少年B型血友病患者具有良好的预防保护作用和出血控制效果。
