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

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

  • J Hematol Oncol. 2021 Feb 25;14(1):37. doi: 10.1186/s13045-021-01047-9.
Heng Mei  # 1,  Xiaofan Liu  # 2,  Yan Li  # 3,  Hu Zhou 4,  Ying Feng 5,  Guangxun Gao 6,  Peng Cheng 7,  Ruibin Huang 8,  Linhua Yang 9,  Jianda Hu 10,  Ming Hou 11,  Yazhou Yao 12,  Li Liu 13,  Yi Wang 14,  Depei Wu 15,  Liansheng Zhang 16,  Changcheng Zheng 17,  Xuliang Shen 18,  Qi Hu 19,  Jing Liu 20,  Jie Jin 21,  Jianmin Luo 22,  Yun Zeng 23,  Sujun Gao 24,  Xiaohui Zhang 25,  Xin Zhou 26,  Qingzhi Shi 27,  Ruixiang Xia 28,  Xiaobao Xie 29,  Zhongxing Jiang 30,  Li Gao 31,  Yuansong Bai 32,  Yan Li 33,  Junye Xiong 34,  Runzi Li 34,  Jianjun Zou 34,  Ting Niu 35,  Renchi Yang 36,  Yu Hu 37
Affiliations

Affiliations

  • 1 Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
  • 2 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.
  • 3 Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
  • 4 Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
  • 5 Department of Hematopathology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 6 The Blood Internal Medicine, The First Affiliated Hospital of Air Force Medical University, Xi'an, China.
  • 7 Hematology Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • 8 Hematology Department, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 9 Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
  • 10 Fujian Medical University Union Hospital, Fuzhou, China.
  • 11 Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
  • 12 Hematology Department, Baoji Central Hospital, Baoji, China.
  • 13 Department of Hematopathology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, China.
  • 14 Department of Hematopathology, Shaanxi Provincial People's Hospital, Xi'an, China.
  • 15 Hematology Department, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • 16 Hematology Department, Lanzhou University Second Hospital, Lanzhou, China.
  • 17 Hematology Department, The First Affiliated Hospital of USTC, Hefei, China.
  • 18 Department of Hematology, Heping Hospital Affiliated To Changzhi Medical College, Changzhi, China.
  • 19 Department of Hematology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai, China.
  • 20 The Third Xiangya Hospital of Central South University, Changsha, China.
  • 21 Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China.
  • 22 Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
  • 23 Department of Hematology, First Affiliated Hospital of Kunming Medical University, KunMing, China.
  • 24 The First Hospital of Jilin University, Changchun, China.
  • 25 Department of Hematology, Peking University People's Hospital, Beijing, China.
  • 26 Hematology Department, Wuxi People's Hospital, Wuxi, China.
  • 27 Hematology Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
  • 28 Hematology Department, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 29 Hematology Department, The First People's Hospital of Changzhou, Changzhou, China.
  • 30 Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 31 Department of Hematology, The Second Affiliated Hospital of Military Medical University PLA, Chongqing, China.
  • 32 Hematology and Oncology, China-Japan Union Hospital of Jilin University, Changchun, China.
  • 33 Hematology Department, The First Hospital of China Medical University, Shenyang, China.
  • 34 Clinical Research & Development, Jiangsu Hengrui Medicine Co., Ltd, Shanghai, China.
  • 35 Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. dr_huyu@126.com.
  • 36 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. rcyang@ihcams.ac.cn.
  • 37 Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China. tingniu@sina.com.
  • # Contributed equally.
PMID: 33632264 DOI: 10.1186/s13045-021-01047-9
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.

Keywords

Hetrombopag; Immune thrombocytopenia; Platelet response; Thrombopoietin receptor agonists.

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