Safety and Efficacy of Peginesatide for the Treatment of Anemia in Participants With Chronic Renal Failure Not on Dialysis (PEARL 2)

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: NCT00598442
Recruitment Status : Completed
First Posted : January 21, 2008
Results First Posted : July 30, 2012
Last Update Posted : February 12, 2013
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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 : 493 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: AFX01-13: 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 : November 2007
Actual Primary Completion Date : July 2009
Actual Study Completion Date : December 2009

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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
Participants received darbepoetin alfa by subcutaneous injection once every 2 weeks, as prescribed. The starting dose was 0.75 microgram per kilogram (mcg/kg) and 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 Received 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 a 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.

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

Inclusion Criteria:

  1. Chronic renal failure with an estimated glomerular filtration rate < 60 milliliters per minute per 1.73 m^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): NCT00598442

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United States, Arizona
Research Facility
Phoenix, Arizona, United States, 85012
United States, Arkansas
Research Facility
Fayetteville, Arkansas, United States, 72703
United States, California
Research Facility
Fountain Valley, California, United States, 92708
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Fullerton, California, United States, 92835
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Granada Hills, California, United States, 91344
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Los Angeles, California, United States, 90022
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San Diego, California, United States, 92123
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Whittier, California, United States, 90603
United States, Florida
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Lauderdale Lakes, Florida, United States, 33313
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Pembroke Pines, Florida, United States, 33028
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Pinecrest, Florida, United States, 33156
United States, Georgia
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Canton, Georgia, United States, 30114
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Columbus, Georgia, United States, 31904
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Marietta, Georgia, United States, 30060
United States, Idaho
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Caldwell, Idaho, United States, 83605
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Meridian, Idaho, United States, 83642
United States, Illinois
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Chicago, Illinois, United States, 60611
United States, Indiana
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Mishawaka, Indiana, United States, 46545
United States, Iowa
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Ames, Iowa, United States, 50010
United States, Louisiana
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Baton Rouge, Louisiana, United States, 70809
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Lafayette, Louisiana, United States, 70506
United States, Maryland
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Rockville, Maryland, United States, 20852
United States, Massachusetts
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Springfield, Massachusetts, United States, 01107
United States, Michigan
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Detroit, Michigan, United States, 48202
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Detroit, Michigan, United States, 48236
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Flint, Michigan, United States, 48504
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Petoskey, Michigan, United States, 49770
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Troy, Michigan, United States, 48098
United States, Missouri
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Washington, Missouri, United States, 63090
United States, New York
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Flushing, New York, United States, 11355
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Williamsville, New York, United States, 14221
United States, North Carolina
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Asheville, North Carolina, United States, 28801
United States, Ohio
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Columbus, Ohio, United States, 43210
United States, Oregon
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Bend, Oregon, United States, 97701
United States, Texas
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Arlington, Texas, United States, 76015
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Houston, Texas, United States, 77004
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San Antonio, Texas, United States, 78229
United States, Vermont
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Burlington, Vermont, United States, 05401
United States, Virginia
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Fairfax, Virginia, United States, 22030
United States, Washington
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Tacoma, Washington, United States, 98405
United States, West Virginia
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Morgantown, West Virginia, United States, 26506
United States, Wisconsin
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Neenah, Wisconsin, United States, 54956
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Sofia, Bulgaria, 1431
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Sofia, Bulgaria, 1606
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Varna, Bulgaria, 9000
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Veliko Tarnovo, Bulgaria, 5000
Czech Republic
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Prague, Czech Republic, 14021
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Tabor, Czech Republic, 39003
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Zdar nad Sazavou, Czech Republic, 591 01
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Demmin, Germany, 17109
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Balatonfured, Hungary, 8230
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Kistarcsa, Hungary, 2143
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Szigetvar, Hungary, 7900
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Lecco, Italy, 23900
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Pavia, Italy, 27100
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Bialystok, Poland, 15 540
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Gdansk, Poland, 80 952
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Katowice, Poland, 40 027
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Zamosc, Poland, 22 400
Puerto Rico
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Ponce, Puerto Rico, 00717-0634
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Iasi, Romania, 700 503
Research Facility
Oradea, Romania, 410469
Research Facility
Timisoara, Romania, 300 736
United Kingdom
Research Facility
London, United Kingdom, SE5 9RS
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: NCT00598442     History of Changes
Other Study ID Numbers: AFX01-13
2007-004146-32 ( EudraCT Number )
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