Phase 3 randomised study of avatrombopag, a novel thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia

Abstract

Avatrombopag, an oral thrombopoietin receptor agonist, was compared with placebo in a 6-month, multicentre, randomised, double-blind, parallel-group Phase 3 study, with an open-label extension phase, to assess the efficacy and safety of avatrombopag (20 mg/day) in adults with chronic immune thrombocytopenia (ITP) and a platelet count <30 × 109 /l (ClinicalTrials.gov identifier NCT01438840). The primary endpoint was the cumulative number of weeks of platelet response (platelet count ≥50 × 109 /l) without rescue therapy for bleeding; secondary endpoints included platelet response rate at day 8 and reductions in the use of concomitant medications. Amongst the 49 patients randomised, avatrombopag (N = 32) was superior to placebo (N = 17) in the median cumulative number of weeks of platelet response (12·4 vs. 0·0 weeks, respectively; P < 0·0001). At day 8, a greater platelet response rate was also observed for patients treated with avatrombopag compared with placebo (65·63% vs. 0·0%; P < 0·0001), and use of concomitant ITP medications was also reduced amongst patients receiving avatrombopag. The safety profile of avatrombopag was consistent with Phase 2 studies; the most common adverse events were headache and contusion. Overall, avatrombopag was well tolerated and efficacious for the treatment of chronic ITP.

Keywords: bleeding disorders; platelet count; platelet disorders; thrombocytopenia; thrombopoietin.

© 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd and British Society for Haematology.

Figures

Figure 1

Study design. (A) Core study. (B) Extension phase. AVA, avatrombopag; CONMED, concomitant medication; E, extension; EOT, end‐of‐treatment; ITP, immune thrombocytopenia; PBO, placebo; qd, once‐daily; R, randomised. *At EOT visit (visit 22), patients could enter the extension phase and receive open‐label avatrombopag therapy. Patients who did not continue into the extension phase entered the dose‐tapering and follow‐up phase. †Only for patients who did not enter the extension phase. ‡Optional entry into the open‐label extension phase. §The screening visit and day 1 baseline/randomisation visit platelet counts were averaged to obtain the baseline platelet count value. The two samples were obtained ≥48 h and ≤2 weeks apart and the results were available prior to randomisation. Therefore, an additional screening platelet count may have been required due to issues with scheduling. ‖Patients who discontinued early who met the criteria for a lack of treatment effect may have moved directly into the open‐label extension phase. [Colour figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Subject disposition. (A) Core study. (B) Extension phase. N/n, number of patients. [Colour figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Median (Q1, Q3) platelet count over time. (A) Core study (FAS). (B) Extension phase (modified FAS). FAS, full analysis set; ITP, immune thrombocytopenia; Med, medication; n, number of patients; Q1/3, quartile 1/3. [Colour figure can be viewed at http://wileyonlinelibrary.com]