Aflac Cancer and Blood Disorders Center, Emory University, Atlanta, GA, USA.
Division of Hematology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
Expert Rev Hematol. 2023 Jul-Dec;16(10):793-801. doi: 10.1080/17474086.2023.2247160. Epub 2023 Sep 7.
To determine the immunogenicity, safety, and efficacy of rurioctocog alfa pegol in previously untreated patients (PUPs) with severe hemophilia A (HA).
This prospective, phase 3 study (NCT02615691) was conducted in PUPs, or patients with ≤2 exposure days (EDs) prior to screening, aged <6 years with severe HA. The primary endpoint was incidence of factor VIII (FVIII) inhibitor development. This protocol-specified interim analysis was conducted after 50 patients had completed ≥50 EDs without developing FVIII inhibitors or had developed a confirmed inhibitor at any time.
Of the enrolled patients, 59/80 (73.8%) received ≥1 dose of rurioctocog alfa pegol; 54 received prophylaxis, and 35 on-demand treatment. Incidence of inhibitor development was 0.19 (10/52). Total annualized bleeding rate (95% CIs) was 3.2 (2.0-5.0) for patients receiving prophylaxis and 3.2 (1.6-6.3) for on-demand treatment. Hemostatic efficacy of most bleedings was rated as 'excellent' or 'good' after 24 hours (122/131 [93.1%]) and at resolution (161/170 [94.7%]). Five patients received ≥1 dose of rurioctocog alfa pegol for immune tolerance induction (ITI) and 1 patient was defined as having ITI success. Thirteen patients experienced 14 treatment-related adverse events, including 10 cases of FVIII inhibitor development.
This is the first prospective study of rurioctocog alfa pegol for the treatment of PUPs with severe HA.
This trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02615691).
评估在未曾接受治疗的重度 A 型血友病（HA）患者（PUP）中，聚乙二醇化重组八因子（rurioctocog alfa pegol）的免疫原性、安全性和疗效。
这是一项前瞻性的 3 期研究（NCT02615691），共纳入 80 名 PUP 患者，这些患者在筛选前的暴露天数（ED）≤2 岁，且患有重度 HA。主要终点为凝血因子 VIII（FVIII）抑制剂的发生率。在 50 名患者完成≥50 个 ED 且未发生 FVIII 抑制剂或在任何时间发生确认的抑制剂后，进行了本方案规定的中期分析。
在入组的患者中，59/80（73.8%）名患者接受了≥1 剂 rurioctocog alfa pegol；54 名患者接受了预防治疗，35 名患者按需治疗。抑制剂的发生率为 0.19（10/52）。接受预防治疗的患者年化出血率（95%CI）为 3.2（2.0-5.0），按需治疗为 3.2（1.6-6.3）。24 小时后（131 例中的 122 例[93.1%]）和出血解决时（170 例中的 161 例[94.7%]），大多数出血的止血效果被评为“优秀”或“良好”。5 名患者接受了≥1 剂 rurioctocog alfa pegol 进行免疫耐受诱导（ITI），1 名患者被定义为 ITI 成功。13 名患者经历了 14 次治疗相关的不良事件，包括 10 例 FVIII 抑制剂的发展。
这是首例前瞻性研究，评估了聚乙二醇化重组八因子治疗重度 A 型血友病的 PUP 患者。
该试验在 ClinicalTrials.gov 注册（CT.gov 标识符：NCT02615691）。
