Phase 2 study of avatrombopag in Japanese patients with chronic liver disease and thrombocytopenia.

Abstract

Avatrombopag, a thrombopoietin receptor agonist, can reduce the need for platelet transfusions or rescue interventions for bleeding in patients with chronic liver disease (CLD) and thrombocytopenia undergoing scheduled procedures. A model analysis indicated that the effect of avatrombopag on platelet production was reduced in East Asian versus non-East Asian patients; however, the difference was deemed not clinically significant. Furthermore, a subgroup analysis of pooled Phase 3 trials showed similar avatrombopag efficacy across racial subgroups. The aim of this Phase 2 study was to corroborate the efficacy and safety of avatrombopag in Japanese patients with thrombocytopenia due to CLD. Japanese patients with CLD and thrombocytopenia were randomized to receive placebo or avatrombopag 20, 40, or 60mg daily for 5days. The primary endpoint was responder rate in platelet counts at Visit 4 (10-13days after treatment initiation), defined as the proportion of patients with platelet count ≥50×109 /L and ≥20×109 /L increase from baseline. Thirty-nine patients were randomized and completed the study (placebo, n=11; avatrombopag 20mg, n=7; 40mg, n=11; 60mg, n=10). Avatrombopag treatment was associated with significant increases in responder rate at Visit 4 in the 40mg (63.6%; p=0.004) and 60mg (40%; p=0.024) groups versus placebo (9.1%). Avatrombopag was well tolerated and no new safety signals were detected. Efficacy and safety results from this study were consistent with previous studies in patients with CLD and thrombocytopenia undergoing elective procedures, supporting treatment with avatrombopag in the Japanese population. gov identifier: NCT02227693.