A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia

作者：Heng Mei, Xiaofan Liu, Yan Li, Hu Zhou, Ying Feng, Guangxun Gao, Cheng Peng, Ruibin Huang, Linhua Yang, Jianda Hu, Ming Hou, Yazhou Yao, Li Liu, Yi Wang, Depei Wu, Liansheng Zhang, Changcheng Zheng, Xuliang Shen, Qi Hu, Jing Liu, Jie Jin, Jianmin Luo, Yun Zeng, Sujun Gao, Xiaohui Zhang, Xin Zhou, Qingzhi Shi, Ruixiang Xia, Xiaobao Xie, Zhongxing Jiang, Li Gao, Yuansong Bai, Yan Li, Junye Xiong, Runzi Li, Jianjun Zou, Ting Niu, Renchi Yang, Yu Hu · 发表于：Journal of Hematology & Oncology · 年份：2021 · DOI：10.1186/s13045-021-01047-9 · 被引用次数：73 · 研究领域：Platelet Disorders and Treatments、Cell Adhesion Molecules Research、Heparin-Induced Thrombocytopenia and Thrombosis

Abstract 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 9 /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 week...