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

NCT ID: NCT00598273

Last Updated: 2013-02-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

490 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-10-31

Study Completion Date

2010-02-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Chronic Renal Failure Chronic Kidney Disease Anemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Peginesatide 0.025 mg/kg

Group Type EXPERIMENTAL

peginesatide

Intervention Type DRUG

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).

Peginesatide 0.04 mg/kg

Group Type EXPERIMENTAL

peginesatide

Intervention Type DRUG

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.

Darbepoetin Alfa

Group Type ACTIVE_COMPARATOR

Darbepoetin alfa

Intervention Type DRUG

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.

Interventions

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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).

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Omontys Hematide AF37702 Injection Omontys Hematide AF37702 Injection Aranesp

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Takeda

INDUSTRY

Sponsor Role collaborator

Affymax

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Vice President, Clinical Development

Role: STUDY_DIRECTOR

Affymax

Locations

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Montgomery, Alabama, United States

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Tempe, Arizona, United States

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Hot Springs, Arkansas, United States

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Bakersfield, California, United States

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Chula Vista, California, United States

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Glendale, California, United States

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Huntington Beach, California, United States

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Los Angeles, California, United States

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Orange, California, United States

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Paramount, California, United States

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Pasadena, California, United States

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Riverside, California, United States

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San Dimas, California, United States

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Stanford, California, United States

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Whittier, California, United States

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Whittier, California, United States

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Yuba City, California, United States

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Thornton, Colorado, United States

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Washington D.C., District of Columbia, United States

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Holly Hill, Florida, United States

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Hudson, Florida, United States

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Miami, Florida, United States

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Ocala, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Augusta, Georgia, United States

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Honolulu, Hawaii, United States

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Chicago, Illinois, United States

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Evergreen Park, Illinois, United States

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Hines, Illinois, United States

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Evansville, Indiana, United States

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Lafayette, Indiana, United States

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Wichita, Kansas, United States

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Shreveport, Louisiana, United States

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Bethesda, Maryland, United States

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Fall River, Massachusetts, United States

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Worcester, Massachusetts, United States

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Midland, Michigan, United States

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Columbus, Mississippi, United States

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Kansas City, Missouri, United States

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Northfield, New Jersey, United States

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Toms River, New Jersey, United States

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Binghamton, New York, United States

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Great Neck, New York, United States

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Mineola, New York, United States

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Charlotte, North Carolina, United States

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Oklahoma City, Oklahoma, United States

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Bend, Oregon, United States

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Portland, Oregon, United States

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Allentown, Pennsylvania, United States

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Erie, Pennsylvania, United States

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Johnstown, Pennsylvania, United States

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Providence, Rhode Island, United States

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Orangeburg, South Carolina, United States

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Rock Hill, South Carolina, United States

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Clarksville, Tennessee, United States

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Knoxville, Tennessee, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

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Corpus Christi, Texas, United States

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Corsicana, Texas, United States

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Edinburg, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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Salem, Virginia, United States

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Bluefield, West Virginia, United States

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Caguas, , Puerto Rico

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Ponce, , Puerto Rico

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San Juan, , Puerto Rico

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San Juan, , Puerto Rico

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Countries

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United States Puerto Rico

References

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Macdougall IC, Provenzano R, Sharma A, Spinowitz BS, Schmidt RJ, Pergola PE, Zabaneh RI, Tong-Starksen S, Mayo MR, Tang H, Polu KR, Duliege AM, Fishbane S; PEARL Study Groups. Peginesatide for anemia in patients with chronic kidney disease not receiving dialysis. N Engl J Med. 2013 Jan 24;368(4):320-32. doi: 10.1056/NEJMoa1203166.

Reference Type RESULT
PMID: 23343062 (View on PubMed)

Fishbane S, Schiller B, Locatelli F, Covic AC, Provenzano R, Wiecek A, Levin NW, Kaplan M, Macdougall IC, Francisco C, Mayo MR, Polu KR, Duliege AM, Besarab A; EMERALD Study Groups. Peginesatide in patients with anemia undergoing hemodialysis. N Engl J Med. 2013 Jan 24;368(4):307-19. doi: 10.1056/NEJMoa1203165.

Reference Type DERIVED
PMID: 23343061 (View on PubMed)

Other Identifiers

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AFX01-11

Identifier Type: -

Identifier Source: org_study_id

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