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

February 6, 2013 updated by: Affymax

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

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.

Study Overview

Status

Completed

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Actual)

493

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Aranesp
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
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
Experimental: Peginesatide 0.04 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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and Weeks 25-36

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants Who Received Red Blood Cell (RBC) Transfusions During the Correction and Evaluation Periods
Time Frame: Weeks 0 to 36
Weeks 0 to 36
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.
Weeks 0 to 36

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Affymax

Collaborators

Takeda

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2007

Primary Completion (Actual)

July 1, 2009

Study Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

January 10, 2008

First Submitted That Met QC Criteria

January 18, 2008

First Posted (Estimate)

January 21, 2008

Study Record Updates

Last Update Posted (Estimate)

February 12, 2013

Last Update Submitted That Met QC Criteria

February 6, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AFX01-13
  • 2007-004146-32 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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