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Open Access Highly Accessed Research article

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

Anatole Besarab1*, Steven N Zeig2, Edouard R Martin3, Pablo E Pergola4, Frederick C Whittier5, Raja I Zabaneh6, Brigitte Schiller7, Martha Mayo8, Carol A Francisco8, Krishna R Polu8 and Anne-Marie Duliege8

Author Affiliations

1 Henry Ford Hospital, Detroit, MI, USA

2 Pines Clinical Research, Pembroke Pines, FL, USA

3 South Florida Nephrology Associates, Lauderdale Lakes, FL, USA

4 Renal Associates PA, San Antonio, TX, USA

5 Clinical Research Ltd, Canton, OH, USA

6 Northwest Louisiana Nephrology, Shreveport, LA, USA

7 Satellite Healthcare, San Jose, CA, USA

8 Affymax, Inc, Palo Alto, CA, USA

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BMC Nephrology 2012, 13:95  doi:10.1186/1471-2369-13-95

Published: 30 August 2012

Abstract

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

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