An open-label, unit dose-finding study of AMG 531, a novel thrombopoiesis-stimulating peptibody, in patients with immune thrombocytopenic purpura.
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.
Newland
Adrian
A
Barts and the London School of Medicine and Dentistry, Queen Mary, London, UK.
Caulier
Marie T
MT
Kappers-Klunne
Mies
M
Schipperus
Martin R
MR
Lefrere
Francois
F
Zwaginga
Jaap J
JJ
Christal
Jenny
J
Chen
Chien-Feng
CF
Nichol
Janet L
JL
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
D002352:Carrier Proteins; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim