Dose-finding study of peginesatide for anemia correction in chronic kidney disease patients

Abstract

Background and objectives: Peginesatide is a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent. We report the first assessment of its efficacy and safety in correcting renal anemia in a population of 139 nondialysis chronic kidney disease patients.

Design, setting, participants, & measurements: Chronic kidney disease patients who were not on dialysis and not receiving treatment with erythropoiesis-stimulating agents in the 12 weeks before study drug administration were sequentially assigned to one of 10 cohorts; cohorts differed in starting peginesatide dose (different body weight-based or absolute doses), route of administration (intravenous or subcutaneous), and frequency of administration (every 4 or 2 weeks).

Results: Across all cohorts, 96% of patients achieved a hemoglobin response. A dose-response relationship was evident for hemoglobin increase. Comparable subcutaneous and intravenous peginesatide doses produced similar hemoglobin responses. Rapid rates of hemoglobin rise and hemoglobin excursions >13 g/dl tended to occur more frequently with every-2-weeks dosing than they did with every-4-weeks dosing. The range of final median doses in the every-4-weeks dosing groups was 0.019 to 0.043 mg/kg. Across all cohorts, 20% of patients reported serious adverse events (one patient had a possibly drug-related serious event) and 81% reported adverse events (11.5% reported possibly drug-related events); these events were consistent with those routinely observed in this patient population.

Conclusions: This study suggests that peginesatide administered every 4 weeks can increase and maintain hemoglobin in nondialysis chronic kidney disease patients. Additional long-term data in larger groups of patients are required to further elucidate the efficacy and safety of this peptide-based erythropoiesis-stimulating agent.

Trial registration: ClinicalTrials.gov NCT00228436.

Figures

Figure 1.

Patient disposition.

Figure 2.

Mean hemoglobin change from baseline. (A) In SC Q4W Cohorts. (B) With matched peginesatide starting doses delivered subcutaneously (Cohort A) or intravenously (Cohort D). (C) With equivalent (i.e., the same dose over a 4-week time period) peginesatide starting doses delivered Q4W (Cohort A) or Q2W (Cohort E). Q2W, every 2 weeks; Q4w, every 4 weeks.

Figure 3.

Median peginesatide doses in the every-4-weeks cohorts, by injection.