An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients

BMC Nephrology

Research Article

Anne-Marie Duliege¹  Krishna R Polu¹  Carol A Francisco¹  Martha Mayo¹  Frederick C Whittier²  Anatole Besarab³  Raja I Zabaneh⁴  Steven N Zeig⁵  Pablo E Pergola⁶  Brigitte Schiller⁷  Edouard R Martin⁸ 

[1] Affymax, Inc, Palo Alto, CA, USA;Clinical Research Ltd, Canton, OH, USA;Henry Ford Hospital, Detroit, MI, USA;Northwest Louisiana Nephrology, Shreveport, LA, USA;Pines Clinical Research, Pembroke Pines, FL, USA;Renal Associates PA, San Antonio, TX, USA;Satellite Healthcare, San Jose, CA, USA;South Florida Nephrology Associates, Lauderdale Lakes, FL, USA;

关键词: Anemia;    Chronic kidney disease;    Erythropoiesis-stimulating agent;    Epoetin alfa;    Hemodialysis;    Peginesatide;   

DOI  :  10.1186/1471-2369-13-95

 received in 2012-02-19, accepted in 2012-08-27,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundPeginesatide is a peptide-based erythropoiesis-stimulating agent that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. The primary objective of this phase 2 dose-finding study was to determine the once-monthly peginesatide dosing strategy that would maintain hemoglobin within ±1.0 g/dL of baseline values after conversion from epoetin alfa; the safety of peginesatide was evaluated concurrently.MethodsChronic hemodialysis patients on stable regimens of epoetin alfa were sequentially assigned to cohorts that differed on (1) how the peginesatide starting dose was determined (using a single epoetin alfa–to-peginesatide dose conversion ratio or a tiered, weight-based or absolute-dose conversion table) and on (2) whether or not a 1-week erythropoiesis-stimulating agent-free interval was used. Peginesatide doses were titrated to maintain hemoglobin levels within ±1.0 g/dL from baseline.ResultsA total of 164 patients were enrolled and received intravenous peginesatide every 4 weeks for up to 6 doses; the duration of the study including follow-up was ≤29 weeks. Overall, the proportion of patients with hemoglobin levels within ±1.0 g/dL of baseline increased over the course of the study from 39% (Weeks 2–13) to 54% (Weeks 18–25). Cohorts that used tiered dose conversion tables trended towards having more stable peginesatide doses than did those cohorts that used a single dose conversion ratio. Moreover, cohorts that used an erythropoiesis-stimulating agent-free interval did not have the substantial initial increase in hemoglobin levels that was seen in those cohorts that did not use such an interval. In this study, the safety profile of peginesatide was consistent with those of marketed erythropoiesis-stimulating agents.ConclusionsThe results of this study were used to guide the dosing regimens used subsequently in phase 3 studies. Once-monthly peginesatide is feasible in hemodialysis patients.Trial registrationClinicalTrials.gov registration: NCT00228449

【 授权许可】

CC BY   
© Besarab et al.; licensee BioMed Central Ltd. 2012