AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP

James B. Bussel, David J. Kuter, James N. George, Robert McMillan, Louis M. Aledort, George T. Conklin, Alan E. Lichtin, Roger M. Lyons, Jorge Nieva, Jeffrey S. Wasser, Israel Wiznitzer, Reggie Kelly, Chien Feng Chen, Janet L. Nichol

Research output: Contribution to journalArticle

389 Citations (Scopus)

Abstract

BACKGROUND: Most current treatments for chronic immune thrombocytopenic purpura (ITP) act by decreasing platelet destruction. In a phase 1-2 study, we administered a thrombopoiesis-stimulating protein, AMG 531, to patients with ITP. METHODS: In phase 1, 24 patients who had received at least one treatment for ITP were assigned to escalating-dose cohorts of 4 patients each and given two identical doses of AMG 531 (0.2 to 10 μg per kilogram of body weight). In phase 2, 21 patients were randomly assigned to receive six weekly subcutaneous injections of AMG 531 (1, 3, or 6 μg per kilogram) or placebo. The primary objective was to assess the safety of AMG 531; the secondary objective was to evaluate platelet counts during and after treatment. RESULTS: No major adverse events that could be attributed directly to AMG 531 occurred during the treatment period; 4 of 41 patients had transient post-treatment worsening of thrombocytopenia. In phase 1, a platelet count that was within the targeted range (50,000 to 450,000 per cubic millimeter) and at least twice the baseline count was achieved in 4 of 12 patients given 3, 6, or 10 μg of AMG 531 per kilogram. Overall, a platelet count of at least 50,000 per cubic millimeter was achieved in 7 of 12 patients, including 3 with counts exceeding 450,000 per cubic millimeter. Increases in the platelet count were dose-dependent; mean peak counts were 163,000, 309,000, and 746,000 per cubic millimeter with 3, 6, and 10 μg of AMG 531 per kilogram, respectively. In phase 2, the targeted platelet range was achieved in 10 of 16 patients treated with 1 or 3 μg of AMG 531 per kilogram per week for 6 weeks. Mean peak counts were 135,000, 241,000, and 81,000 per cubic millimeter in the groups that received the 1-μg dose, the 3-μg dose, and placebo, respectively. CONCLUSIONS: AMG 531 caused no major adverse events and increased platelet counts in patients with ITP. (ClinicalTrials.gov number, NCT00111475.)

Original languageEnglish
Pages (from-to)1672-1681
Number of pages10
JournalNew England Journal of Medicine
Volume355
Issue number16
DOIs
StatePublished - Oct 19 2006
Externally publishedYes

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Thrombopoiesis
Idiopathic Thrombocytopenic Purpura
Platelet Count
Proteins
Blood Platelets
Placebos
Therapeutics
Subcutaneous Injections
Thrombocytopenia
Body Weight
Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bussel, J. B., Kuter, D. J., George, J. N., McMillan, R., Aledort, L. M., Conklin, G. T., ... Nichol, J. L. (2006). AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. New England Journal of Medicine, 355(16), 1672-1681. https://doi.org/10.1056/NEJMoa054626

AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. / Bussel, James B.; Kuter, David J.; George, James N.; McMillan, Robert; Aledort, Louis M.; Conklin, George T.; Lichtin, Alan E.; Lyons, Roger M.; Nieva, Jorge; Wasser, Jeffrey S.; Wiznitzer, Israel; Kelly, Reggie; Chen, Chien Feng; Nichol, Janet L.

In: New England Journal of Medicine, Vol. 355, No. 16, 19.10.2006, p. 1672-1681.

Research output: Contribution to journalArticle

Bussel, JB, Kuter, DJ, George, JN, McMillan, R, Aledort, LM, Conklin, GT, Lichtin, AE, Lyons, RM, Nieva, J, Wasser, JS, Wiznitzer, I, Kelly, R, Chen, CF & Nichol, JL 2006, 'AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP', New England Journal of Medicine, vol. 355, no. 16, pp. 1672-1681. https://doi.org/10.1056/NEJMoa054626
Bussel JB, Kuter DJ, George JN, McMillan R, Aledort LM, Conklin GT et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. New England Journal of Medicine. 2006 Oct 19;355(16):1672-1681. https://doi.org/10.1056/NEJMoa054626
Bussel, James B. ; Kuter, David J. ; George, James N. ; McMillan, Robert ; Aledort, Louis M. ; Conklin, George T. ; Lichtin, Alan E. ; Lyons, Roger M. ; Nieva, Jorge ; Wasser, Jeffrey S. ; Wiznitzer, Israel ; Kelly, Reggie ; Chen, Chien Feng ; Nichol, Janet L. / AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. In: New England Journal of Medicine. 2006 ; Vol. 355, No. 16. pp. 1672-1681.
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abstract = "BACKGROUND: Most current treatments for chronic immune thrombocytopenic purpura (ITP) act by decreasing platelet destruction. In a phase 1-2 study, we administered a thrombopoiesis-stimulating protein, AMG 531, to patients with ITP. METHODS: In phase 1, 24 patients who had received at least one treatment for ITP were assigned to escalating-dose cohorts of 4 patients each and given two identical doses of AMG 531 (0.2 to 10 μg per kilogram of body weight). In phase 2, 21 patients were randomly assigned to receive six weekly subcutaneous injections of AMG 531 (1, 3, or 6 μg per kilogram) or placebo. The primary objective was to assess the safety of AMG 531; the secondary objective was to evaluate platelet counts during and after treatment. RESULTS: No major adverse events that could be attributed directly to AMG 531 occurred during the treatment period; 4 of 41 patients had transient post-treatment worsening of thrombocytopenia. In phase 1, a platelet count that was within the targeted range (50,000 to 450,000 per cubic millimeter) and at least twice the baseline count was achieved in 4 of 12 patients given 3, 6, or 10 μg of AMG 531 per kilogram. Overall, a platelet count of at least 50,000 per cubic millimeter was achieved in 7 of 12 patients, including 3 with counts exceeding 450,000 per cubic millimeter. Increases in the platelet count were dose-dependent; mean peak counts were 163,000, 309,000, and 746,000 per cubic millimeter with 3, 6, and 10 μg of AMG 531 per kilogram, respectively. In phase 2, the targeted platelet range was achieved in 10 of 16 patients treated with 1 or 3 μg of AMG 531 per kilogram per week for 6 weeks. Mean peak counts were 135,000, 241,000, and 81,000 per cubic millimeter in the groups that received the 1-μg dose, the 3-μg dose, and placebo, respectively. CONCLUSIONS: AMG 531 caused no major adverse events and increased platelet counts in patients with ITP. (ClinicalTrials.gov number, NCT00111475.)",
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AU - Kuter, David J.

AU - George, James N.

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AU - Aledort, Louis M.

AU - Conklin, George T.

AU - Lichtin, Alan E.

AU - Lyons, Roger M.

AU - Nieva, Jorge

AU - Wasser, Jeffrey S.

AU - Wiznitzer, Israel

AU - Kelly, Reggie

AU - Chen, Chien Feng

AU - Nichol, Janet L.

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N2 - BACKGROUND: Most current treatments for chronic immune thrombocytopenic purpura (ITP) act by decreasing platelet destruction. In a phase 1-2 study, we administered a thrombopoiesis-stimulating protein, AMG 531, to patients with ITP. METHODS: In phase 1, 24 patients who had received at least one treatment for ITP were assigned to escalating-dose cohorts of 4 patients each and given two identical doses of AMG 531 (0.2 to 10 μg per kilogram of body weight). In phase 2, 21 patients were randomly assigned to receive six weekly subcutaneous injections of AMG 531 (1, 3, or 6 μg per kilogram) or placebo. The primary objective was to assess the safety of AMG 531; the secondary objective was to evaluate platelet counts during and after treatment. RESULTS: No major adverse events that could be attributed directly to AMG 531 occurred during the treatment period; 4 of 41 patients had transient post-treatment worsening of thrombocytopenia. In phase 1, a platelet count that was within the targeted range (50,000 to 450,000 per cubic millimeter) and at least twice the baseline count was achieved in 4 of 12 patients given 3, 6, or 10 μg of AMG 531 per kilogram. Overall, a platelet count of at least 50,000 per cubic millimeter was achieved in 7 of 12 patients, including 3 with counts exceeding 450,000 per cubic millimeter. Increases in the platelet count were dose-dependent; mean peak counts were 163,000, 309,000, and 746,000 per cubic millimeter with 3, 6, and 10 μg of AMG 531 per kilogram, respectively. In phase 2, the targeted platelet range was achieved in 10 of 16 patients treated with 1 or 3 μg of AMG 531 per kilogram per week for 6 weeks. Mean peak counts were 135,000, 241,000, and 81,000 per cubic millimeter in the groups that received the 1-μg dose, the 3-μg dose, and placebo, respectively. CONCLUSIONS: AMG 531 caused no major adverse events and increased platelet counts in patients with ITP. (ClinicalTrials.gov number, NCT00111475.)

AB - BACKGROUND: Most current treatments for chronic immune thrombocytopenic purpura (ITP) act by decreasing platelet destruction. In a phase 1-2 study, we administered a thrombopoiesis-stimulating protein, AMG 531, to patients with ITP. METHODS: In phase 1, 24 patients who had received at least one treatment for ITP were assigned to escalating-dose cohorts of 4 patients each and given two identical doses of AMG 531 (0.2 to 10 μg per kilogram of body weight). In phase 2, 21 patients were randomly assigned to receive six weekly subcutaneous injections of AMG 531 (1, 3, or 6 μg per kilogram) or placebo. The primary objective was to assess the safety of AMG 531; the secondary objective was to evaluate platelet counts during and after treatment. RESULTS: No major adverse events that could be attributed directly to AMG 531 occurred during the treatment period; 4 of 41 patients had transient post-treatment worsening of thrombocytopenia. In phase 1, a platelet count that was within the targeted range (50,000 to 450,000 per cubic millimeter) and at least twice the baseline count was achieved in 4 of 12 patients given 3, 6, or 10 μg of AMG 531 per kilogram. Overall, a platelet count of at least 50,000 per cubic millimeter was achieved in 7 of 12 patients, including 3 with counts exceeding 450,000 per cubic millimeter. Increases in the platelet count were dose-dependent; mean peak counts were 163,000, 309,000, and 746,000 per cubic millimeter with 3, 6, and 10 μg of AMG 531 per kilogram, respectively. In phase 2, the targeted platelet range was achieved in 10 of 16 patients treated with 1 or 3 μg of AMG 531 per kilogram per week for 6 weeks. Mean peak counts were 135,000, 241,000, and 81,000 per cubic millimeter in the groups that received the 1-μg dose, the 3-μg dose, and placebo, respectively. CONCLUSIONS: AMG 531 caused no major adverse events and increased platelet counts in patients with ITP. (ClinicalTrials.gov number, NCT00111475.)

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