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 lg, 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-lg 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 lg/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 lg/kg increased platelet counts.

Romiplostim safety and efficacy for immune thrombocytopenia in clinical practice: 2-year results of 72 adults in a romiplostim compassionate-use program

“…8 It has been reported to be a highly effective treatment for both splenectomized and nonsplenectomized patients in pivotal clinical studies [9][10][11][12] and has been accorded Food and Drug Administration approval for the treatment of ITP patients in the United States, after failure of a first-line therapy (either corticosteroids or intravenous immunoglobulins [IVIg]). More recently, romiplostim was licensed in Europe after splenectomy failure or contraindication.…”

Moving towards a new era in the management of chronic immune thrombocytopenia

“…Platelet numbers peaked at 12-16 days, returning to baseline at 28 days [40]. Platelet response in adults with ITP and low platelet counts were first reported in a dose-finding assessment of romiplostim given as two injections separated by a 15-day interval [43].…”

“…Patients who had been enrolled in the phase III studies [45], and other studies assessing romiplostim for treatment of ITP [43,44], were eligible for a long-term extension open-label trial, irrespective of whether they had received romiplostim or placebo [49]. The most recent reported data, (July 2008) is based on an Intent to Treat population of 223 patients; 99 of whom (44%) were splenectomised, and 34 patients (15%) were on concurrent ITP therapy at study entry [50,51].…”

“…The most recent reported data, (July 2008) is based on an Intent to Treat population of 223 patients; 99 of whom (44%) were splenectomised, and 34 patients (15%) were on concurrent ITP therapy at study entry [50,51]. Previous treatment with romiplostim varied from no exposure to 24 weeks [43][44][45]. Dose adjustment was made according to platelet count, to a maximum of 10 μg/kg, weekly.…”

Romiplostim: an alternative treatment option besides rituximab for the management of steroid refractory idiopathic thrombocytopenic purpura

“…A slightly higher response rate was noted in non-splenectomized patients in comparison to splenectomized patients. Overall, the side effect profile of romiplostim is very good, with the most frequent side effect being headaches which are noted in 50% of the patients [3]. Other serious side effects include a temporary exacerbation of the thrombocytopenia following the cessation of therapy.…”