First-in-patient study of hetrombopag in patients with chronic idiopathic thrombocytopenic purpura.

Background Idiopathic thrombocytopenic purpura (ITP) especially refractory and (or) relapsed ITP, is a serious and global health burden and its clinical treatment is far from being satisfied. Hetrombopag is a novel small-molecule thrombopoietin receptor agonist for the treatment of chronic idiopathic thrombocytopenic purpura (CITP). Objectives This first-in-patient study aimed to investigate the safety, pharmacokinetics, and anticipated therapeutic dose of hetrombopag in CITP patients. Methods In this multicenter, first-in-patient study, CITP patients received hetrombopag in a dose escalation (2,5mg, 5mg, or 7.5 mg/day) cohort. All patients received hetrombopag in fasting condition once daily for two weeks. Results Of 44 patients screened, 32 were enrolled and treated. Most adverse events were graded 1-2 (i.e. mild to moderate), and the incidence and severity were similar for three study cohorts. The pharmacokinetics of hetrombopag were found to be nonlinear with greater than dose-proportional. 12.5% of patients (1/8) in the 2.5 mg/ day cohort, 58.3% of patients (7/12) in the 5 mg/day cohort, 66.7% of patients (8/12) in the 7.5 mg/day cohort reached the primary study endpoint of a platelet count exceeding 50 × 109 /L on day 28. Conclusion Hetrombopag was well tolerated and preliminary efficacious. Efficacy, safety and PK data suggested that 7.5 mg hetrombopag once daily was the anticipated therapeutic dose of hetrombopag in CITP patients and have been recommended to investigate in the later confirmatory clinical study of hetrombopag.