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

BMC Nephrology

Anne-Marie Duliege⁷  Krishna R Polu⁷  Carol A Francisco⁷  Martha Mayo⁷  Brigitte Schiller¹  Raja I Zabaneh²  Frederick C Whittier³  Pablo E Pergola⁴  Edouard R Martin⁶  Steven N Zeig⁸  Anatole Besarab⁵ 

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

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

Others  :  1083116
DOI  :  10.1186/1471-2369-13-95

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

【 摘 要 】

Background

Peginesatide 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.

Methods

Chronic 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.

Results

A 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.

Conclusions

The 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 registration

ClinicalTrials.gov registration: NCT00228449

【 授权许可】

   
2012 Besarab et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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