NCT00597753

Safety & Efficacy of Peginesatide for Maintenance Treatment of Anemia in Participants With Chronic Kidney Disease on Hemodialysis

AFX01-12: A Phase 3, Randomized, Active-controlled, Open-label, Multi-center Study of the Safety and Efficacy of Peginesatide for the Maintenance Treatment of Anemia in Hemodialysis Patients Previously Treated With Epoetin Alfa

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 803 (actual)
• Sponsor: Affymax · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of the study was to evaluate the safety and efficacy of peginesatide in the maintenance treatment of anemia in participants on dialysis.

Detailed description

Anemia associated with chronic kidney disease is due to several factors, primarily the inability of the diseased kidneys to produce adequate amounts of endogenous erythropoietin. Ancillary factors include the shortened lifespan of red blood cells, iron and other nutritional deficiencies, infection, and inflammation. The presence and severity of anemia are related to the duration and extent of kidney failure. Anemia is associated with increased mortality, increased likelihood of hospitalization, reduced cognitive function, and increased left ventricular hypertrophy and heart failure. Erythropoiesis stimulating agents (ESAs) have been established as a treatment for anemia in chronic renal failure subjects, and have improved the management of anemia over alternatives such as transfusion. Peginesatide is a parenteral formulation developed for the treatment of anemia in patients with chronic kidney disease. Peginesatide binds to and activates the human erythropoietin receptor, and stimulates erythropoiesis in human red cell precursors in a manner similar to other known erythropoiesis-stimulating agents. Eligible participants were randomized in a 2:1 ratio to peginesatide administered once every 4 weeks or to continued treatment with epoetin alfa administered 1-3 times each week, respectively. Total commitment time for this study was 4 weeks of screening followed by a minimum of 52 weeks of study treatment. To evaluate the cardiovascular safety of peginesatide, a cardiovascular composite safety endpoint (CSE) was defined for use in prospectively planned analyses which combined cardiovascular safety data from the four Phase 3 peginesatide studies (NCT00598273, NCT00597753, NCT00598442, and NCT00597584). The CSE consisted of six events: death, stroke, myocardial infarction, and serious adverse events of congestive heart failure, unstable angina, and arrhythmia. An independent Event Review Committee (ERC) was used to provide blinded adjudication of potential CSE events.

Conditions

• Chronic Renal Failure
• Chronic Kidney Disease
• Anemia

Interventions

Type	Name	Description
DRUG	peginesatide	Participants received peginesatide by intravenous injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa dose. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 grams per deciliter (g/dL) and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.
DRUG	Epoetin Alfa	Participants continued to receive commercially available epoetin alfa by intravenous injection, at the same starting dose and frequency as received during the last week of the Screening Period, with the first study dose of epoetin alfa administered after randomization at Week 0. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.

Timeline

• Start date: 2007-09-01
• Primary completion: 2009-07-01
• Completion: 2010-01-01
• First posted: 2008-01-18
• Last updated: 2013-02-12
• Results posted: 2012-07-30

Locations

89 sites across 1 country: United States