Center for Pediatric Oncology and Hematology, Children's Hospital, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania.
1st Department of Pediatrics, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
J Thromb Haemost. 2020 Sep;18 Suppl 1(Suppl 1):15-25. doi: 10.1111/jth.15036.
N8-GP (turoctocog alfa pegol; Esperoct , Novo Nordisk A/S, Bagsvaerd, Denmark) is a glycoPEGylated, extended half-life human recombinant factor VIII (FVIII).
Here, we report end-of-trial safety and efficacy results from the completed N8-GP pathfinder5 trial.
pathfinder5 (NCT01731600) was a multi-national, open-label, single-arm, non-randomized, non-controlled trial in previously treated male patients aged <12 years old with severe hemophilia A that comprised a main and an extension phase. During the main phase, patients received twice-weekly N8-GP 60 IU/kg for 50 exposure days (~26 weeks). During the extension phase, patients received the same regimen until the end of trial (first patient in main phase, 20 February 2013; trial end, 28 September 2018).
Sixty-eight patients were exposed to N8-GP for a median time of ~4.9 years on regimen. Of the 63 patients who started in the extension phase, 62 completed the trial. No FVIII inhibitors (≥0.6 BU) or other safety concerns were detected. The overall estimated annualized bleeding rate was 1.08 (median 0.81), and nearly 20% of patients had no bleeds during the entire trial. The proportion of patients with no annual bleeds increased with time, with 56% of patients experiencing no bleeds and 86% experiencing no spontaneous bleeds during the fourth year of exposure. All baseline target joints of patients who participated in both phases of this trial were resolved in slightly over 2 years.
Overall, data from the completed pathfinder5 trial show that long-term (median 4.9 years) N8-GP treatment was efficacious and well tolerated in previously treated pediatric patients with severe hemophilia A.
N8-GP（聚乙二醇化重组人凝血因子 VIII，Novo Nordisk A/S，丹麦巴格斯韦德）是一种糖基化、延长半衰期的人重组凝血因子 VIII（FVIII）。
本研究报告了已完成的 N8-GP 探索者 5 期临床试验的终期安全性和疗效结果。
探索者 5 期（NCT01731600）是一项多中心、开放性、单臂、非随机、非对照的临床试验，纳入了 68 例曾接受治疗的 12 岁以下男性重度 A 型血友病患者，该试验包括主要阶段和扩展阶段。在主要阶段，患者接受每周 2 次、60IU/kg 的 N8-GP 治疗，共 50 个暴露日（约 26 周）。在扩展阶段，患者接受相同的治疗方案，直至试验结束（主阶段首位患者于 2013 年 2 月 20 日入组，试验于 2018 年 9 月 28 日结束）。
68 例患者按方案接受 N8-GP 治疗，中位时间约为 4.9 年。63 例开始进入扩展阶段的患者中，62 例完成了试验。未检测到 FVIII 抑制剂（≥0.6BU）或其他安全性问题。总体估计年化出血率为 1.08（中位数 0.81），近 20%的患者在整个试验期间无出血。随着时间的推移，无出血年的患者比例增加，4 年暴露期间，56%的患者无出血，86%的患者无自发性出血。本试验两阶段所有患者的基线靶关节均在略超过 2 年内得到缓解。
总体而言，探索者 5 期试验的完成数据表明，长期（中位 4.9 年）N8-GP 治疗可有效且耐受良好，适用于曾接受治疗的重度 A 型血友病儿童患者。
