评价人凝血酶原复合物治疗乙型血友病患者的安全性和有效性

To evaluate the safety and effectiveness of human prothrombin complex in the treatment of hemophilia B patients

目的:评价博雅生物制药集团股份有限公司研制的人凝血酶原复合物治疗乙型血友病患者的有效性和安全性。方法:采用多中心、开放、单组设计开展Ⅲ期临床研究,5家研究中心共入组36例乙型血友病受试者,根据受试者出血的严重程度及凝血因子Ⅸ的需求输注人凝血酶原复合物,以第一次输注结束后30 min凝血因子Ⅸ活性输注效率值为主要疗效指标,以每次出血首次输注后24 h出血症状和体征改善情况及第一次输注结束后30 min凝血因子Ⅸ活性的升高幅度为次要疗效指标。结果:36例受试者均纳入安全性分析集(SS)、全分析集(FAS)和符合方案分析集(PPS),第一次输注结束后30 min凝血因子Ⅸ活性输注效率值为(104.600±21.518)%。第一次输注结束后24 h的出血症状和体征改善评分,基线出血(受试者百分比)和基线后出血(事件百分比)评分优良率分别为83.3%和94.6%,改善率分别为16.7%和5.4%,有效率(优良率+改善率)均为100%。第一次输注结束后30 min凝血因子Ⅸ活性的升高幅度为(29.300±9.254)%。未出现严重不良事件,未见人凝血因子Ⅱ,Ⅶ,Ⅸ和Ⅹ抗体及新增病毒感染。结论:输注人凝血酶原复合物能够显著提高乙型血友病患者体内的凝血因子Ⅸ活性水平,人凝血酶原复合物总体安全性良好。

Objective:To evaluate the effectiveness and safety of human prothrombin complex developed by our company in the treatment of patients with hemophilia B.Methods:A multi-center,open,single-group design was used to carry out a phase III clinical study.A total of 36 subjects with hemophilia B were enrolled in five research centers,and the human prothrombin complex was infused according to the severity of the bleeding and the level of factorⅨrequired,30 minutes after the end of the first infusion.The value of factorⅨactivity infusion efficiency is the main efficacy index.The improvement in bleeding symptoms and signs 24 hours after the first infusion of each bleeding and the increase in factorⅨactivity 30 minutes after the end of the first infusion are secondary efficacy index.Results:The 36 subjects in this study were included in the safety analysis set(SS),full analysis set(FAS),and protocol analysis set(PPS).The factorⅨactive infusion efficiency value was(104.600±21.518)%30 minutes after the end of the first infusion.The improvement score of bleeding symptoms and signs 24 hours after the end of the first infusion,baseline bleeding(percent of participants)and post-baseline bleeding(percentage of events)scores were:excellent was 83.3%and 94.6%,improved was 16.7%and 5.4%,effective rate(excellent+improved)100.0%.The increase in factorⅨactivity 30 minutes after the end of the first infusion was(29.300±9.254)%.No serious adverse events occurred.No human coagulation factorⅡ,Ⅶ,Ⅸ,Ⅹantibodies and no new virus infection occurred.Conclusion:Infusion of the human prothrombin complex produced by our company can significantly increase the activity level of coagulation factor IX in patients with hemophilia B,and the overall safety of the human prothrombin complex is good.