Safety & Efficacy of Peginesatide for the Treatment of Anemia in Participants With Chronic Renal Failure Not on Dialysis

Phase 3

Completed

Conditions: Chronic Kidney Disease
Anemia
Chronic Renal Failure

Interventions: Drug: peginesatide
Drug: Darbepoetin alfa

Registration Number: NCT00598273

Lead Sponsor: Affymax

Brief Summary: The purpose of this study was to evaluate the safety and efficacy of peginesatide for the treatment of anemia in participants with chronic kidney disease, who are not on dialysis and not on erythropoiesis stimulating agent (ESA) treatment.

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 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.

Study participants received doses of peginesatide administered once every 4 weeks or darbepoetin alfa administered once every 2 weeks. Total commitment time for this study was a 4 week screening period followed by a minimum of 52 weeks of study treatment. Eligible participants were randomized in equal proportions to two peginesatide treatment regimens and one control, darbepoetin alfa, treatment regimen.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 490

Inclusion Criteria

Chronic renal failure with an estimated glomerular filtration rate < 60 milliliter per minute per 1.73m^2 and not expected to begin dialysis for at least 12 weeks.
Two consecutive hemoglobin values ≥ 8.0 g/dL and < 11.0 g/dL within 4 weeks prior to randomization.

Exclusion Criteria

Females who are pregnant or breast-feeding.
Treatment with an ESA in the 12 weeks prior to randomization.
Known intolerance to any ESA, parenteral iron supplementation, or pegylated molecule.
Prior chronic hemodialysis or chronic peritoneal dialysis treatment.
Known bleeding or coagulation disorder.
Known hematologic disease or cause of anemia other than renal disease
Poorly controlled hypertension
Evidence of active malignancy within one year prior to randomization.
A scheduled kidney transplant

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Peginesatide 0.025 mg/kg	peginesatide	-
Peginesatide 0.04 mg/kg	peginesatide	-
Darbepoetin Alfa	Darbepoetin alfa	-

Primary Outcome Measures

Name	Time	Method
Mean Change in Hemoglobin Between Baseline and the Evaluation Period	Baseline and Weeks 25-36	The baseline hemoglobin value is defined as the mean of three hemoglobin values: the two most recent hemoglobin values taken prior to the day of randomization and the value obtained on the day of randomization. The mean hemoglobin during the Evaluation Period for each participant is calculated as the mean of the available hemoglobin values during Study Weeks 25 through 36.

Secondary Outcome Measures

Name	Time	Method
Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Correction and Evaluation Periods	Weeks 0 to 36
Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods.	Weeks 0 to 36	A hemoglobin response is defined as hemoglobin increase of ≥ 1.0 gram per deciliter (g/dL) above baseline and a hemoglobin ≥ 11.0 g/dL without RBC transfusion during the previous 8 weeks.