Avatrombopag for adult chronic primary immune thrombocytopenia: a randomized phase 3 trial in China

Heng Mei; Hu Zhou; Ming Hou; Jing Sun; Lei Zhang; Jianmin Luo; Zhongxing Jiang; Xu Ye; Yajing Xu; Jun Lu; Hui Wang; Aimin Hui; Yongchun Zhou; Yu Hu

doi:10.1016/j.rpth.2023.102158

Avatrombopag for adult chronic primary immune thrombocytopenia: a randomized phase 3 trial in China

Res Pract Thromb Haemost. 2023 Jul 26;7(6):102158. doi: 10.1016/j.rpth.2023.102158. eCollection 2023 Aug.

Authors

Heng Mei¹, Hu Zhou², Ming Hou³, Jing Sun⁴, Lei Zhang^{5

6}, Jianmin Luo⁷, Zhongxing Jiang⁸, Xu Ye⁹, Yajing Xu¹⁰, Jun Lu¹¹, Hui Wang¹¹, Aimin Hui¹¹, Yongchun Zhou¹², Yu Hu¹

Affiliations

¹ Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
³ Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, China.
⁴ Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
⁵ State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China.
⁶ Tianjin Institute of Health Science, Tianjin, China.
⁷ Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
⁸ Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁹ Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
¹⁰ Department of Hematology, Xiangya Hospital, Central South University; Hunan Hematology Oncology Clinical Medical Research Center, Changsha, China.
¹¹ R&D Center, Fosun Pharma, Shanghai, China.
¹² Wanbang Biopharmaceuticals, Xuzhou, China.

Abstract

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder with decreased platelet counts and increased bleeding risk.

Objectives: To evaluate the efficacy and safety of avatrombopag, a second-generation oral thrombopoietin receptor agonist, for the treatment of Chinese patients with chronic primary ITP.

Methods: This multicenter, randomized, double-blind, placebo-controlled phase 3 study (CTR20210431) consisted of a 6-week double-blind core treatment phase followed by a 20-week, open-label extension phase. Chinese adults with chronic primary ITP for at least 12 months and a platelet count <30 × 10⁹/L were randomized (2:1) to receive avatrombopag (initial dose of 20 mg/day) or matched placebo. The primary endpoint was the proportion of subjects with a platelet count ≥50 × 10⁹/L at week 6 of the core treatment phase in absence of rescue therapy.

Results: In total, 74 patients were randomized (avatrombopag: N = 48; placebo: N = 26) between March 5, 2021, and August 6, 2021; all of whom entered the extension phase (72 received avatrombopag up to 26 weeks). At week 6 of the core study, the platelet response (≥50 x 10⁹/L) rate was significantly higher in the avatrombopag group (77.1%; 95% CI, 62.7, 88.0) vs placebo (7.7%; 95% CI, 1.0, 25.1); the treatment difference was 69.4% (95% CI, 56.2, 86.3; P < .0001). During the 6-week core study, treatment-emergent adverse events were reported in 41 (85.4%) and 20 (76.9%) patients in the avatrombopag and placebo groups, respectively. The most common avatrombopag-related treatment-emergent adverse events were upper respiratory tract infection (14/48 [29.2%]), increased platelet count (13/48 [27.1%]) and headache (7/48 [14.6%]).

Conclusion: Avatrombopag was efficacious and generally well tolerated in Chinese patients with chronic primary ITP, with comparable efficacy and safety to previous reports in Western patients.

Keywords: China; avatrombopag; immune thrombocytopenia; phase 3; randomized; thrombopoietin receptor.