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

January 10, 2008
February 6, 2013
November 2007
July 2009   (final data collection date for primary outcome measure)
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.
The primary efficacy endpoint of this study is the mean change in Hgb between baseline and the Evaluation Period. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00598442 on ClinicalTrials.gov Archive Site
  • 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.
Not Provided
Not Provided
Not Provided
 
Safety and Efficacy of Peginesatide for the Treatment of Anemia in Participants With Chronic Renal Failure Not on Dialysis
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Chronic Renal Failure
  • Chronic Kidney Disease
  • Anemia
  • 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
  • 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
  • Experimental: Peginesatide 0.025 mg/kg
    Intervention: Drug: peginesatide
  • Experimental: Peginesatide 0.04 mg/kg
    Intervention: Drug: peginesatide
  • Active Comparator: Darbepoetin alfa
    Intervention: Drug: Darbepoetin alfa

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
493
December 2009
July 2009   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Bulgaria,   Czech Republic,   Germany,   Hungary,   Italy,   Poland,   Puerto Rico,   Romania,   United Kingdom
 
NCT00598442
AFX01-13, 2007-004146-32
Yes
Affymax
Affymax
Takeda
Study Director: Vice President, Clinical Development Affymax
Affymax
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP