Safety & Efficacy of Peginesatide for the Treatment of Anemia in Participants With Chronic Renal Failure Not on Dialysis (PEARL 1)
Chronic Renal Failure
Chronic Kidney Disease
Drug: Darbepoetin alfa
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||AFX01-11: A Phase 3, Randomized, Active-controlled, Open-label, Multi-center Study of the Safety and Efficacy of Peginesatide for the Correction of Anemia in Patients With Chronic Renal Failure (CRF) Not on Dialysis and Not on Erythropoiesis Stimulating Agent (ESA) Treatment|
- Mean Change in Hemoglobin Between Baseline and the Evaluation Period [ Time Frame: Baseline and Weeks 25-36 ] [ Designated as safety issue: No ]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.
- Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Correction and Evaluation Periods [ Time Frame: Weeks 0 to 36 ] [ Designated as safety issue: No ]
- Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods. [ Time Frame: Weeks 0 to 36 ] [ Designated as safety issue: No ]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.
|Study Start Date:||October 2007|
|Study Completion Date:||February 2010|
|Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
|Experimental: Peginesatide 0.025 mg/kg||
Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.025 milligram per kilogram (mg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).
|Experimental: Peginesatide 0.04 mg/kg||
Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.04 mg/kg and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
|Active Comparator: Darbepoetin Alfa||
Drug: Darbepoetin alfa
As prescribed, starting dose of 0.75 microgram per kilogram (mcg/kg) administered by subcutaneous injection once every 2 weeks. The dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
Other Name: Aranesp
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00598273
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|Study Director:||Vice President, Clinical Development||Affymax|