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

NCT ID: NCT00598442

Last Updated: 2013-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 493 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2009-12-31

Brief Summary

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

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

Chronic Renal Failure; Chronic Kidney Disease; Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Interventions

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

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.

Intervention Type: DRUG

Other Intervention Names

Omontys; Hematide; AF37702 Injection; Omontys; Hematide; AF37702 Injection; Aranesp

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: collaborator

Affymax

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vice President, Clinical Development

Role: STUDY_DIRECTOR

Affymax

Locations

Research Facility

Phoenix, Arizona, United States

Research Facility

Fayetteville, Arkansas, United States

Research Facility

Fountain Valley, California, United States

Research Facility

Fullerton, California, United States

Research Facility

Granada Hills, California, United States

Research Facility

Los Angeles, California, United States

Research Facility

San Diego, California, United States

Research Facility

Whittier, California, United States

Research Facility

Lauderdale Lakes, Florida, United States

Research Facility

Pembroke Pines, Florida, United States

Research Facility

Pinecrest, Florida, United States

Research Facility

Canton, Georgia, United States

Research Facility

Columbus, Georgia, United States

Research Facility

Marietta, Georgia, United States

Research Facility

Caldwell, Idaho, United States

Research Facility

Meridian, Idaho, United States

Research Facility

Chicago, Illinois, United States

Research Facility

Mishawaka, Indiana, United States

Research Facility

Ames, Iowa, United States

Research Facility

Baton Rouge, Louisiana, United States

Research Facility

Lafayette, Louisiana, United States

Research Facility

Rockville, Maryland, United States

Research Facility

Springfield, Massachusetts, United States

Research Facility

Detroit, Michigan, United States

Research Facility

Detroit, Michigan, United States

Research Facility

Flint, Michigan, United States

Research Facility

Petoskey, Michigan, United States

Research Facility

Troy, Michigan, United States

Research Facility

Washington, Missouri, United States

Research Facility

Flushing, New York, United States

Research Facility

Williamsville, New York, United States

Research Facility

Asheville, North Carolina, United States

Research Facility

Columbus, Ohio, United States

Research Facility

Bend, Oregon, United States

Research Facility

Arlington, Texas, United States

Research Facility

Houston, Texas, United States

Research Facility

San Antonio, Texas, United States

Research Facility

Burlington, Vermont, United States

Research Facility

Fairfax, Virginia, United States

Research Facility

Tacoma, Washington, United States

Research Facility

Morgantown, West Virginia, United States

Research Facility

Neenah, Wisconsin, United States

Research Facility

Sofia, , Bulgaria

Research Facility

Sofia, , Bulgaria

Research Facility

Varna, , Bulgaria

Research Facility

Veliko Tarnovo, , Bulgaria

Research Facility

Prague, , Czechia

Research Facility

Tábor, , Czechia

Research Facility

Zdar, , Czechia

Research Facility

Demmin, , Germany

Research Facility

Balatonfüred, , Hungary

Research Facility

Kistarcsa, , Hungary

Research Facility

Szigetvár, , Hungary

Research Facility

Lecco, , Italy

Research Facility

Pavia, , Italy

Research Facility

Bialystok, , Poland

Research Facility

Gdansk, , Poland

Research Facility

Katowice, , Poland

Research Facility

Zamość, , Poland

Research Facility

Ponce, , Puerto Rico

Research Facility

Iași, , Romania

Research Facility

Oradea, , Romania

Research Facility

Timișoara, , Romania

Research Facility

London, , United Kingdom

Countries

United States; Bulgaria; Czechia; Germany; Hungary; Italy; Poland; Puerto Rico; Romania; United Kingdom

References

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

2007-004146-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AFX01-13

Identifier Type: -

Identifier Source: org_study_id