一项多中心、随机 III 期临床试验：新型促血小板生成素受体激动剂治疗免疫性血小板减少症。
A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia.
机构信息
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
Thrombosis and Hemostasis Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, 300020, China.
出版信息
J Hematol Oncol. 2021 Feb 25;14(1):37. doi: 10.1186/s13045-021-01047-9.
BACKGROUND
Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients.
METHODS
Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 10/L) after 8 weeks of treatment.
RESULTS
The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83-68.63; p < 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39-86.87; p < 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment.
CONCLUSIONS
In ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile. Trial registration Clinical trials.gov NCT03222843 , registered July 19, 2017, retrospectively registered.
背景
在 ITP 患者中，Hetrombopag 是一种新型的血小板生成素受体激动剂，在 I 期研究中发现可增加血小板计数并降低出血风险。这项 III 期研究旨在评估 Hetrombopag 在 ITP 患者中的疗效和安全性。
方法
未对先前治疗无反应或复发的患者接受每日一次 2.5 或 5mg Hetrombopag 的初始剂量治疗（定义为 HETROM-2.5 或 HETROM-5 组）或随机接受匹配安慰剂双盲治疗，为期 10 周。接受安慰剂并完成 10 周治疗的患者转换为接受 Eltrombopag 治疗，双盲期间接受 Hetrombopag 治疗的患者在随后的 14 周开放标签治疗期间继续接受 Hetrombopag 治疗。主要终点是治疗 8 周后应答者的比例（定义为血小板计数≥50×10/L 的患者）。
结果
HETROM-2.5（58.9%；优势比[OR]25.97，95%置信区间[CI]9.83-68.63；p<0.0001）和 HETROM-5（64.3%；OR 32.81，95%CI 12.39-86.87；p<0.0001）组的主要终点显著高于安慰剂组（5.9%）。在治疗的 8 周内，Hetrombopag 在实现血小板反应以及降低出血风险和使用抢救治疗方面也优于安慰剂。Hetrombopag 的持久血小板反应在 24 周内得以维持。最常见的不良事件是上呼吸道感染（42.2%）、尿路感染（17.1%）、免疫性血小板减少性紫癜（17.1%）和血尿（15%），接受 24 周 Hetrombopag 治疗。
结论
在 ITP 患者中，Hetrombopag 有效且耐受性良好，安全性可管理。试验注册临床试验.gov NCT03222843，2017 年 7 月 19 日注册，回顾性注册。
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