title: An open-label, unit dose-finding study of AMG 531, a novel thrombopoiesis-stimulating peptibody, in patients with immune thrombocytopenic purpura.
abstract: 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 microg, administered subcutaneously on days 1 and 15 (or day 22 if the day 15 platelet count was >50 x 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 x 10(9)/l. Sixteen patients (10 women) were enrolled. The 500-microg 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 microg/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 microg/kg increased platelet counts.
authors.affiliation: Barts and the London School of Medicine and Dentistry, Queen Mary, London, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Newland
authors.forename: Marie T
authors.initials: MT
authors.lastname: Caulier
authors.forename: Mies
authors.initials: M
authors.lastname: Kappers-Klunne
authors.forename: Martin R
authors.initials: MR
authors.lastname: Schipperus
authors.forename: Francois
authors.initials: F
authors.lastname: Lefrere
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: Zwaginga
authors.forename: Jenny
authors.initials: J
authors.lastname: Christal
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Chen
authors.forename: Janet L
authors.initials: JL
authors.lastname: Nichol
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000188:drug therapy*; D011961:Receptors, Fc / Q000008:administration & dosage* / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins; D034061:Thrombopoiesis / Q000187:drug effects*; D013926:Thrombopoietin; D016896:Treatment Outcome
chemical_list: D002352:Carrier Proteins; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim