B 结构域缺失重组凝血因子 VIII（SCT800）用于预防治疗青少年和成年重型 A 型血友病患者的药代动力学、疗效和安全性评估。
Pharmacokinetic, efficacy and safety evaluation of B-domain-deleted recombinant FVIII (SCT800) for prophylactic treatment in adolescent and adult patients with severe haemophilia A.
机构信息
State Key Laboratory of Experimental Hematology, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, National Clinical Research Center for Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Hematology & Blood Diseases Hospital, Tianjin, China.
Department of Hematology, Xiangya Hospital, Central South University, Changsha, China.
出版信息
Haemophilia. 2021 Sep;27(5):814-822. doi: 10.1111/hae.14350. Epub 2021 Jun 5.
INTRODUCTION
SCT800 is a recombinant human B-domain-deleted coagulation factor VIII (BDDrFVIII) developed in China.
AIM
To evaluate the repeat pharmacokinetics (PKs), efficacy, and safety of SCT800 in previously treated Chinese adolescent and adult patients with severe haemophilia A.
METHODS
A phase III, multicentre, prospective, open-label, single-arm trial was conducted at 12 medical centres. Subjects received treatment for 24 weeks. PKs were assessed at the initial and repeated dosing 24 weeks later. The primary endpoint was annualized bleeding rate (ABR). Breakthrough bleeding episodes and inhibitor development were assessed.
RESULTS
A total of 71 of 73 patients completed the study, and 18 were enrolled for the repeat PK investigation. Total exposure was 5643 exposure days. Overall, SCT800 showed comparable repeat PK profiles. The total ABR was 2.82 (95% confidence interval 2.01-3.96). During prophylaxis, 43.8% of patients had no bleeding episodes. The majority (89.4%) of bleeding episodes were controlled with 1-2 injections of SCT800, the success rate (defined as 'excellent' or 'good' haemostatic response) for the treatment of bleeding episodes was 92.6%. The incidence of treatment-related adverse events was 53.4%. Drug-related AE incidence was 4.1%. The observed AEs were similar to those of other coagulation factor VIII, but lower in frequency. No subject developed an inhibitor, and no other safety concerns were identified.
CONCLUSIONS
SCT800 has robust PK characteristics, and is safe and efficacious for the prophylaxis and treatment of bleeding episodes in previously treated adolescent and adult patients with severe haemophilia A.
简介
SCT800 是一种在中国开发的重组人 B 结构域缺失凝血因子 VIII（BDDrFVIII）。
目的
评估 SCT800 在既往接受治疗的中国青少年和成年重度 A 型血友病患者中的重复药代动力学（PK）、疗效和安全性。
方法
一项在中国 12 家医学中心进行的、为期 24 周的、多中心、前瞻性、开放性、单臂 III 期临床试验。受试者接受治疗 24 周。在初始剂量和重复剂量 24 周后评估 PKs。主要终点是年化出血率（ABR）。评估突破性出血事件和抑制剂的发展。
结果
共有 73 例患者中的 71 例完成了研究，18 例患者入组重复 PK 研究。总暴露天数为 5643 天。总体而言，SCT800 表现出可重复的 PK 特征。总 ABR 为 2.82（95%置信区间 2.01-3.96）。在预防治疗中，43.8%的患者无出血事件。大多数（89.4%）出血事件用 1-2 次 SCT800 注射即可控制，出血事件的治疗成功率（定义为“优秀”或“良好”的止血反应）为 92.6%。治疗相关不良事件的发生率为 53.4%。药物相关 AE 发生率为 4.1%。观察到的 AE 与其他凝血因子 VIII 相似，但频率较低。无患者发生抑制剂，未发现其他安全性问题。
结论
SCT800 具有稳健的 PK 特征，用于预防和治疗既往接受治疗的青少年和成年重度 A 型血友病患者的出血事件是安全有效的。
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