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

This study has been completed.
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
Affymax
ClinicalTrials.gov Identifier:
NCT00598442
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: AFX01-13: 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

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 Received 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 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.


Enrollment: 493
Study Start Date: November 2007
Study Completion Date: December 2009
Primary Completion Date: July 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
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

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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00598442

  Show 64 Study Locations
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: NCT00598442     History of Changes
Other Study ID Numbers: AFX01-13, 2007-004146-32
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
Bulgaria: Bulgarian Drug Agency
Bulgaria: Ethics committee
Czech Republic: State Institute for Drug Control
Czech Republic: Ethics Committee
Germany: Federal Institute for Drugs and Medical Devices
Germany: Ethics Commission
Hungary: National Institute of Pharmacy
Hungary: Scientific and Medical Research Council Ethics Committee
Italy: The Italian Medicines Agency
Italy: Ethics Committee
Poland: The Central Register of Clinical Trials
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Poland: Ethics Committee
Romania: National Medicines Agency
Romania: Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

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 August 27, 2014