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

This study has been completed.
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
Affymax
ClinicalTrials.gov Identifier:
NCT00598273
First received: January 10, 2008
Last updated: February 6, 2013
Last verified: February 2013
  Purpose

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 Intervention Phase
Chronic Renal Failure
Chronic Kidney Disease
Anemia
Drug: peginesatide
Drug: Darbepoetin alfa
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Affymax:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 490
Study Start Date: October 2007
Study Completion Date: February 2010
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00598273

  Hide Study Locations
Locations
United States, Alabama
Research Facility
Montgomery, Alabama, United States, 36106
United States, Arizona
Research Facility
Tempe, Arizona, United States, 85306
United States, Arkansas
Research Facility
Hot Springs, Arkansas, United States, 71901
United States, California
Research Facility
Bakersfield, California, United States, 93309
Research Facility
Chula Vista, California, United States, 91910
Research Facility
Glendale, California, United States, 91204
Research Facility
Huntington Beach, California, United States, 92646
Research Facility
Los Angeles, California, United States, 90095
Research Facility
Orange, California, United States, 92868
Research Facility
Paramount, California, United States, 90723
Research Facility
Pasadena, California, United States, 91106
Research Facility
Riverside, California, United States, 92505
Research Facility
San Dimas, California, United States, 91773
Research Facility
Stanford, California, United States, 94305-6203
Research Facility
Whittier, California, United States, 90606
Research Facility
Whittier, California, United States, 90603
Research Facility
Yuba City, California, United States, 95991
United States, Colorado
Research Facility
Thornton, Colorado, United States, 80031
United States, District of Columbia
Research Facility
Washington, District of Columbia, United States, 20037
United States, Florida
Research Facility
Holly Hill, Florida, United States, 32117
Research Facility
Hudson, Florida, United States, 34667
Research Facility
Miami, Florida, United States, 33173
Research Facility
Ocala, Florida, United States, 34471
Research Facility
Orlando, Florida, United States, 32804
Research Facility
Tampa, Florida, United States, 33614
United States, Georgia
Research Facility
Augusta, Georgia, United States, 30901
United States, Hawaii
Research Facility
Honolulu, Hawaii, United States, 96817
United States, Illinois
Research Facility
Chicago, Illinois, United States, 60616
Research Facility
Evergreen Park, Illinois, United States, 60805
Research Facility
Hines, Illinois, United States, 60141
United States, Indiana
Research Facility
Evansville, Indiana, United States, 47714
Research Facility
Lafayette, Indiana, United States, 47904
United States, Kansas
Research Facility
Wichita, Kansas, United States, 67214
United States, Louisiana
Research Facility
Shreveport, Louisiana, United States, 71101
United States, Maryland
Research Facility
Bethesda, Maryland, United States, 20814
United States, Massachusetts
Research Facility
Fall River, Massachusetts, United States, 02720
Research Facility
Worcester, Massachusetts, United States, 01608
United States, Michigan
Research Facility
Midland, Michigan, United States, 48640
United States, Mississippi
Research Facility
Columbus, Mississippi, United States, 39705
United States, Missouri
Research Facility
Kansas City, Missouri, United States, 64128
United States, New Jersey
Research Facility
Northfield, New Jersey, United States, 08225
Research Facility
Toms River, New Jersey, United States, 08755
United States, New York
Research Facility
Binghamton, New York, United States, 13903
Research Facility
Great Neck, New York, United States, 11021
Research Facility
Mineola, New York, United States, 11501
United States, North Carolina
Research Facility
Charlotte, North Carolina, United States, 28208
United States, Oklahoma
Research Facility
Oklahoma City, Oklahoma, United States, 73116
United States, Oregon
Research Facility
Bend, Oregon, United States, 97701
Research Facility
Portland, Oregon, United States, 97210
United States, Pennsylvania
Research Facility
Allentown, Pennsylvania, United States, 18103
Research Facility
Erie, Pennsylvania, United States, 16507
Research Facility
Johnstown, Pennsylvania, United States, 15905
United States, Rhode Island
Research Facility
Providence, Rhode Island, United States, 02904
United States, South Carolina
Research Facility
Orangeburg, South Carolina, United States, 29118
Research Facility
Rock Hill, South Carolina, United States, 29732
United States, Tennessee
Research Facility
Clarksville, Tennessee, United States, 37043
Research Facility
Knoxville, Tennessee, United States, 37923
Research Facility
Nashville, Tennessee, United States, 37205
United States, Texas
Research Facility
Austin, Texas, United States, 78705
Research Facility
Corpus Christi, Texas, United States, 78404
Research Facility
Corsicana, Texas, United States, 75110
Research Facility
Edinburg, Texas, United States, 78539
Research Facility
Houston, Texas, United States, 77030
Research Facility
Houston, Texas, United States, 77099
Research Facility
San Antonio, Texas, United States, 78229
Research Facility
San Antonio, Texas, United States, 78215
United States, Virginia
Research Facility
Salem, Virginia, United States, 24153
United States, West Virginia
Research Facility
Bluefield, West Virginia, United States, 24701
Puerto Rico
Research Facility
Caguas, Puerto Rico, 00725
Research Facility
Ponce, Puerto Rico, 00716
Research Facility
San Juan, Puerto Rico, 00918
Research Facility
San Juan, Puerto Rico, 00909
Sponsors and Collaborators
Affymax
Takeda
Investigators
Study Director: Vice President, Clinical Development Affymax
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Affymax
ClinicalTrials.gov Identifier: NCT00598273     History of Changes
Other Study ID Numbers: AFX01-11
Study First Received: January 10, 2008
Results First Received: April 26, 2012
Last Updated: February 6, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Affymax:
anemia
chronic kidney disease
CKD
chronic renal failure
CRF
erythropoietin
EPO
erythropoiesis stimulating agent
ESA
Hematide™
hemoglobin
Hb
Hgb
Omontys
peginesatide
red blood cell
red blood cell production

Additional relevant MeSH terms:
Anemia
Kidney Diseases
Kidney Failure, Chronic
Renal Insufficiency
Renal Insufficiency, Chronic
Hematologic Diseases
Urologic Diseases
Darbepoetin alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014