Safety and efficacy of hetrombopag in patients with chronic immune thrombocytopenia: a single-arm, open-label, multi-center phase 1 study

Abstract

BACKGROUND Thrombopoietin receptor agonists (TPO-RAs) are promising therapeutic strategy for patients with immune thrombocytopenia (ITP). We conducted this phase 1 trial (NCT02614846) to evaluate the preliminary efficacy and safety of hetrombopag (a TPO-RA) in patients with ITP. METHODS Patients with ITP who had an insufficient response or had progressed on at least one standard treatment for ITP were given hetrombopag orally at an initial dose of 5 mg once daily for up to 6 weeks. The primary endpoint was the proportion of patients who achieved platelet counts of ≥50×109/L at week 6. RESULTS A total of 37 eligible patients received hetrombopag treatment. This study met its primary endpoint, 22 (59.5%, 95% CI: 42.1-75.3) patients responded to hetrombopag, achieving platelet counts ≥50×109/L at week 6. Of the 29 (78.4%, 95% CI: 61.8-90.2%) patients who responded at least once during the study, the median time from treatment initiation to first response was 2.1 weeks (95% CI: 1.3-4.1 weeks). The median accumulative response duration was 3.1 weeks [interquartile range (IQR), 2.1-4.1 weeks]. The incidence of bleeding was reduced with hetrombopag treatment compared to the baseline. Adverse events (AEs) occurred in 32 (86.5%) patients and treatment-related AEs occurred in 13 (35.1%) patients. Two (5.4%) serious AEs were reported, but neither were treatment related. The dose was modified in one (2.7%) patient due to an AE. There were no incidences of treatment discontinuation/interruption or death. CONCLUSIONS Hetrombopag showed preliminary activity in elevating platelet counts and reducing bleeding in patients with chronic ITP who had received at least one standard therapy. It was well-tolerated.