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

Clin J Am Soc Nephrol. 2011 Nov;6(11):2579-86. doi: 10.2215/CJN.10831210. Epub 2011 Sep 22.

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.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia / blood
  • Anemia / drug therapy*
  • Anemia / etiology
  • Biomarkers / blood
  • Chronic Disease
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Hematinics / administration & dosage*
  • Hematinics / adverse effects
  • Hemoglobins / metabolism
  • Humans
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Kidney Diseases / blood
  • Kidney Diseases / complications*
  • Male
  • Middle Aged
  • Peptides / administration & dosage*
  • Peptides / adverse effects
  • Poland
  • Regression Analysis
  • Time Factors
  • Treatment Outcome
  • United Kingdom

Substances

  • Biomarkers
  • Hematinics
  • Hemoglobins
  • Peptides
  • peginesatide

Associated data

  • ClinicalTrials.gov/NCT00228436