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Previous Volume 355:1672-1681 October 19, 2006 Number 16 Next

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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 [ClinicalTrials.gov] .)

Source Information

From the New York Presbyterian Hospital, New York (J.B.B.); Massachusetts General Hospital, Boston (D.J.K.); University of Oklahoma Medical Center, Oklahoma City (J.N.G.); Scripps Cancer Center, La Jolla, CA (R.M., J.N.); Mount Sinai Medical Center, New York (L.M.A.); Diagnostic Clinic of Houston, Houston (G.T.C.); Cleveland Clinic Foundation, Cleveland (A.E.L.); Hematology–Oncology Associates of South Texas, San Antonio, TX (R.M.L.); DeQuattro Community Cancer Center, Manchester, CT (J.S.W.); Broward General Medical Center, Fort Lauderdale, FL (I.W.); and Amgen, Thousand Oaks, CA (R.K., C.-F.C., J.L.N.).

Address reprint requests to Dr. Bussel at Weill Cornell University, Division of Pediatric Hematology, Payson 609, 525 E. 68th St., New York, NY 10021, or at jbussel{at}med.cornell.edu.

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AMG 531 for Chronic ITP
Tauro S., Prasad K., Bussel J. B., Kuter D. J., Nichol J. L.
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N Engl J Med 2007; 356:307-308, Jan 18, 2007. Correspondence

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