Abstract The objective of this open label, phase 1-2, multicentre trial was to evaluate the safety of AMG 531, a novel thrombopoiesis-stimulating peptibody, and its effect on platelet counts in adults with immune thrombocytopenic purpura. Four patients were assigned to each of four unit-dose cohorts: 30, 100, 300 or 500 microg, administered subcutaneously on days 1 and 15 (or day 22 if the day 15 platelet count was >50 x 10(9)/l). Safety was assessed by adverse event (AE) monitoring, clinical laboratory studies and antibody assays. Platelet response was defined as a platelet count double the baseline value and between 50 and 450 x 10(9)/l. Sixteen patients (10 women) were enrolled. The 500-microg cohort was discontinued because the first patient's platelet count became unacceptably high. AEs were generally expected and mild or moderate; the most frequent was headache (eight of 16 patients). Two patients experienced serious AEs related to AMG 531 (severe headache and elevated serum lactic dehydrogenase; thrombocytopenia). Platelet responses occurred with all doses and with a dose equivalent to >/=1 microg/kg in eight of 11 patients. In summary, patients tolerated AMG 531 well at the doses tested. No anti-AMG or antithrombopoietin antibodies were detected. Doses equivalent to >/=1 microg/kg increased platelet counts.