Safety & Efficacy of Peginesatide for the Treatment of Anemia in Participants With Chronic Renal Failure Not on Dialysis (PEARL 1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00598273
Recruitment Status : Completed
First Posted : January 21, 2008
Results First Posted : July 30, 2012
Last Update Posted : February 12, 2013
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Chronic Renal Failure Chronic Kidney Disease Anemia Drug: peginesatide Drug: Darbepoetin alfa Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 490 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : October 2007
Actual Primary Completion Date : March 2009
Actual Study Completion Date : February 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Peginesatide 0.025 mg/kg Drug: peginesatide
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).
Other Names:
  • Omontys
  • Hematide
  • AF37702 Injection

Experimental: Peginesatide 0.04 mg/kg Drug: peginesatide
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.
Other Names:
  • Omontys
  • Hematide
  • AF37702 Injection

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

Primary Outcome Measures :
  1. Mean Change in Hemoglobin Between Baseline and the Evaluation Period [ Time Frame: 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 :
  1. Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Correction and Evaluation Periods [ Time Frame: Weeks 0 to 36 ]
  2. Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods. [ Time Frame: 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 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.
  2. Two consecutive hemoglobin values ≥ 8.0 g/dL and < 11.0 g/dL within 4 weeks prior to randomization.

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00598273

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Montgomery, Alabama, United States, 36106
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Tempe, Arizona, United States, 85306
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Hot Springs, Arkansas, United States, 71901
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Charlotte, North Carolina, United States, 28208
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Salem, Virginia, United States, 24153
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Bluefield, West Virginia, United States, 24701
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Caguas, Puerto Rico, 00725
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Ponce, Puerto Rico, 00716
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San Juan, Puerto Rico, 00909
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San Juan, Puerto Rico, 00918
Sponsors and Collaborators
Study Director: Vice President, Clinical Development Affymax

Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Affymax Identifier: NCT00598273     History of Changes
Other Study ID Numbers: AFX01-11
First Posted: January 21, 2008    Key Record Dates
Results First Posted: July 30, 2012
Last Update Posted: February 12, 2013
Last Verified: February 2013

Keywords provided by Affymax:
chronic kidney disease
chronic renal failure
erythropoiesis stimulating agent
red blood cell
red blood cell production

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Kidney Failure, Chronic
Hematologic Diseases
Urologic Diseases
Darbepoetin alfa