A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia
Abstrak
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 × 109/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.
Topik & Kata Kunci
Penulis (39)
Heng Mei
Xiaofan Liu
Yan Li
Hu Zhou
Ying Feng
Guangxun Gao
Peng Cheng
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
Akses Cepat
- Tahun Terbit
- 2021
- Sumber Database
- DOAJ
- DOI
- 10.1186/s13045-021-01047-9
- Akses
- Open Access ✓