An open‐label, unit dose‐finding study of AMG 531, a novel thrombopoiesis‐stimulating peptibody, in patients with immune thrombocytopenic purpura

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 μ g, administered subcutaneously on days 1 and 15 (or day 22 if the day 15 platelet count was >50 × 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 × 10 9 /l. Sixteen patients (10 women) were enrolled. The 500‐ μ g 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 μ g/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 μ g/kg increased platelet counts.