A phase II, open-label, sequential-cohort, dose-escalation study of romiplostim in Japanese patients with chronic immune thrombocytopenic purpura

Abstract

This phase II, multicenter, open-label, sequential-cohort, dose-escalation study was designed to evaluate the safety and efficacy of romiplostim, a novel peptibody that increases platelet production, in Japanese patients with chronic immune thrombocytopenic purpura (ITP). Sequential cohorts of four patients each received romiplostim (1, 3, or 6 microg/kg) subcutaneously on days 1 and 8 of the dose-escalation phase. Patients who achieved platelet responses (doubling of baseline platelet counts to > or =50 x 10(9)/L) continued romiplostim weekly during the treatment-continuation phase. Romiplostim produced dose-dependent increases in mean and peak platelet counts. Five patients received romiplostim during the treatment-continuation phase, with platelet counts > or =50 x 10(9)/L maintained in approximately half of the weekly assessments. Romiplostim was well tolerated. No severe, serious, or life-threatening adverse events were reported. No binding antibodies to romiplostim or thrombopoietin were detected. Romiplostim is safe and well tolerated in Japanese patients with chronic ITP and is effective in producing platelet count increases, consistent with the results from studies in non-Japanese patients. On the basis of these findings, a starting dose of 3 microg/kg was recommended for phase III evaluation of romiplostim in Japanese patients with chronic ITP.

Integrated analysis of long-term safety in patients with chronic immune thrombocytopaenia (ITP) treated with the thrombopoietin (TPO) receptor agonist romiplostim

“…Updated safety data are provided for over 1000 patients with a mean time on study of 76 weeks. The results reported here are similar to those observed in individual studies and in a prior pooled analysis [3,5,[7][8][9][10][11][12][13][14][15][16][17]. There was no increase in the time-adjusted rates of AEs previously designated to be of interest, including bone marrow reticulin, thrombosis, and malignancy, with longer term treatment with romiplostim (up to more than 5 years for some patients), and no new safety signals emerged.…”

“…These studies were conducted in compliance with all regulatory obligations, including institutional review board and informed consent regulations at each investigational site. The parent studies included (with ClinicalTrials.gov identifiers) phase 2 dose-finding studies (NCT00111475 part B [8] and NCT00515203 [9]), phase 3 studies (NCT00102323 [3], NCT00102336 [3], NCT00603642 [10], and NCT00415532 [11]), and singlearm studies (NCT00111475 part A [8], NCT00117143 [12], NCT00305435 [13], NCT00508820 [14], and NCT00907478 [7]). Subsequent extension/followup studies included two open-label extension studies (NCT00116688 [15] and NCT00440037 [16]) and a bone marrow follow-up study (NCT00861224 [17] from the phase 3 studies NCT00102323 and NCT00102336 [3]).…”

Romiplostim for the treatment of chronic immune thrombocytopenia in adult Japanese patients: a double-blind, randomized Phase III clinical trial

“…Romiplostim was previously assessed in phase 1 and 2 dose-escalation studies in Japanese patients with ITP. In these studies, romiplostim was found to be safe, well tolerated, and effective at increasing platelet counts in a dose-dependent manner [31,32]. Results were generally consistent with those from studies on non-Japanese patients.…”

Thrombopoietin Receptor Agonists: A Critical Review

“…Two second generation agents are currently licensed; one is a peptide bound to an Fc molecule, and the other is a small molecule. Both of these agents have been tested in the largest ITP trials ever performed: thus far in published clinical trial results, over 300 ITP patients have received each agent [4][5][6][7][8][9][10][11] . Currently these agents are also being/have been evaluated for other indications.…”