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

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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 μg/kg) subcutaneously on days 1 and 8 of the dose-escalation phase. Patients who achieved platelet responses (doubling of baseline platelet counts to ≥50 × 109/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 ≥50 × 109/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 μg/kg was recommended for phase III evaluation of romiplostim in Japanese patients with chronic ITP.

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Acknowledgments

This study was sponsored by Amgen KK (Japan). The authors would like to thank Yoshiaki Ogawa, Tokai University; and Kiyoshi Kitamura for providing for study support. M. Ohkura and Y. Sonehara, former employees of Amgen KK, provided biostatistical and study management support, respectively. Editorial support for the manuscript was provided by B. Weichman, PhD, and PAREXEL, and was funded by Amgen Inc.

Conflict of interest statement

D. P. Berger is an employee of Amgen Inc. T. Ohtsu is a former employee of Amgen KK. Y. Shirasugi, K. Ando, S. Hashino, T. Nagasawa, Y. Kurata, Y., Kishimoto, and K. Iwato received research funding from Amgen.

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Authors and Affiliations

  1. Tokai University Hospital, Isehara, Japan

    Yukari Shirasugi & Kiyoshi Ando

  2. Hokkaido University Hospital, Sapporo, Japan

    Satoshi Hashino

  3. Tsukuba University Hospital, Tsukuba, Japan

    Toshiro Nagasawa

  4. Osaka University Hospital, Suita, Japan

    Yoshiyuki Kurata

  5. Kansai Medical University Takii Hospital, Moriguchi, Japan

    Yuji Kishimoto

  6. Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan

    Koji Iwato

  7. Amgen KK, Tokyo, Japan

    Tomoko Ohtsu

  8. Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320-1799, USA

    Dietmar P. Berger

Authors
  1. Yukari Shirasugi
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  2. Kiyoshi Ando
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  3. Satoshi Hashino
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  4. Toshiro Nagasawa
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  5. Yoshiyuki Kurata
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  6. Yuji Kishimoto
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  7. Koji Iwato
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  8. Tomoko Ohtsu
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  9. Dietmar P. Berger
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Correspondence to Dietmar P. Berger.

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Shirasugi, Y., Ando, K., Hashino, S. et al. A phase II, open-label, sequential-cohort, dose-escalation study of romiplostim in Japanese patients with chronic immune thrombocytopenic purpura. Int J Hematol 90, 157–165 (2009). https://doi.org/10.1007/s12185-009-0361-y

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  • DOI: https://doi.org/10.1007/s12185-009-0361-y

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