Institute of Blood Pathology and Transfusion Medicine, National Academy of Medical Sciences of Ukraine, Lviv, Ukraine.
Lebanon Department of Pediatrics, Hotel Dieu de France Hospital, Beirut, Lebanon.
J Thromb Haemost. 2017 Apr;15(4):636-644. doi: 10.1111/jth.13647. Epub 2017 Mar 21.
Essentials rVIII-SingleChain is a novel recombinant factor VIII with covalently bonded heavy and light chains. Efficacy, safety and pharmacokinetics were studied in pediatric patients with severe hemophilia A. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00. rVIII-SingleChain showed excellent hemostatic efficacy and a favorable safety profile.
Background rVIII-SingleChain is a novel B-domain truncated recombinant factor VIII (rFVIII) comprised of covalently bonded FVIII heavy and light chains, demonstrating a high binding affinity to von Willebrand factor. Objectives This phase III study investigated the safety, efficacy and pharmacokinetics of rVIII-SingleChain in previously treated pediatric patients < 12 years of age with severe hemophilia A. Patients/Methods Patients could be assigned to prophylaxis or on-demand therapy by the investigator. For patients assigned to prophylaxis, the treatment regimen and dose were based on the bleeding phenotype. For patients receiving on-demand therapy, dosing was guided by World Federation of Hemophilia recommendations. The primary endpoint was treatment success, defined as a rating of 'excellent' or 'good' on the investigator's clinical assessment of hemostatic efficacy for all treated bleeding events. Results The study enrolled 84 patients (0 to < 6 years, n = 35; ≥ 6 to < 12 years, n = 49); 81 were assigned to prophylaxis and three to an on-demand regimen. Patients accumulated a total of 5239 exposure days (EDs), with 65 participants reaching > 50 EDs. In the 347 bleeds treated and evaluated by the investigator, hemostatic efficacy was rated as excellent or good in 96.3%. The median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.00, 2.20), and the median annualized bleeding rate was 3.69 (Q1, Q3: 0.00, 7.20) across all prophylaxis regimens. No participant developed an inhibitor. Conclusions rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy and a favorable safety profile in a clinical study in children < 12 years of age with severe hemophilia A.
Essentials rVIII-SingleChain 是一种新型的重组因子 VIII（rFVIII），其重链和轻链通过共价键连接。在患有严重血友病 A 的儿科患者中研究了其疗效、安全性和药代动力学。在所有预防方案中，年化自发性出血率中位数为 0.00。rVIII-SingleChain 显示出优异的止血疗效和良好的安全性。
背景：Essentials rVIII-SingleChain 是一种新型的 B 结构域截断重组因子 VIII（rFVIII），由共价键连接的 FVIII 重链和轻链组成，与血管性血友病因子具有高结合亲和力。目的：本 III 期研究调查了先前接受过治疗的 < 12 岁患有严重血友病 A 的儿科患者中 rVIII-SingleChain 的安全性、疗效和药代动力学。
患者可由研究者分配至预防或按需治疗。对于分配至预防治疗的患者，治疗方案和剂量基于出血表型。对于接受按需治疗的患者，剂量由世界血友病联盟建议指导。主要终点是治疗成功，定义为研究者对所有治疗出血事件的止血疗效进行临床评估时的评分“优秀”或“良好”。
该研究共纳入 84 名患者（0 至 < 6 岁，n = 35；≥ 6 至 < 12 岁，n = 49）；81 名患者被分配至预防组，3 名患者被分配至按需治疗组。患者总共累积了 5239 个暴露日（ED），其中 65 名患者达到了 > 50 ED。在由研究者评估和治疗的 347 例出血中，96.3%的止血疗效评为优秀或良好。年化自发性出血率中位数为 0.00（Q1，Q3：0.00，2.20），所有预防方案的年化出血率中位数为 3.69（Q1，Q3：0.00，7.20）。没有患者产生抑制剂。
rVIII-SingleChain 是一种新型 rFVIII 分子，在一项针对 < 12 岁患有严重血友病 A 的儿童的临床研究中，显示出优异的止血疗效和良好的安全性。
