Safety & Efficacy of Peginesatide for Maintenance Treatment of Anemia in Participants With Chronic Kidney Disease on Hemodialysis

NCT ID: NCT00597584

Last Updated: 2013-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 823 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2010-01-31

Brief Summary

The purpose of this study was to evaluate the safety and efficacy of peginesatide in the maintenance treatment of anemia in participants on dialysis.

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 (ESAs) 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.

Eligible participants were randomized in a 2:1 ratio to peginesatide administered once every 4 weeks or to continued treatment with epoetin administered 1-3 times each week, respectively. Total commitment time for this study was 4 weeks of screening followed by a minimum of 52 weeks of study treatment.

To evaluate the cardiovascular safety of peginesatide injection, a composite safety endpoint (CSE) was defined for use in prospectively planned analyses which combined cardiovascular safety data from the four Phase 3 peginesatide injection 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

Group Type: EXPERIMENTAL

peginesatide

Intervention Type: DRUG

Participants received peginesatide by intravenous (IV) or subcutaneous (SC) injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa or beta dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa or beta dose. Participants who received epoetin alfa or beta IV at the time of screening received peginesatide IV during the study, and participants who received epoetin alfa or beta SC at the time of screening received peginesatide SC during the study.

The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.

Epoetin

Group Type: ACTIVE_COMPARATOR

Epoetin alfa or Epoetin beta

Intervention Type: DRUG

Participants continued to receive commercially available epoetin alfa or beta by intravenous or subcutaneous injection, at the same starting dose, frequency and route of administration as received during the last week of the Screening Period, with the first study dose of epoetin alfa or beta administered after randomization at Week 0.

The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.

Interventions

peginesatide

Participants received peginesatide by intravenous (IV) or subcutaneous (SC) injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa or beta dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa or beta dose. Participants who received epoetin alfa or beta IV at the time of screening received peginesatide IV during the study, and participants who received epoetin alfa or beta SC at the time of screening received peginesatide SC during the study.

The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.

Intervention Type: DRUG

Epoetin alfa or Epoetin beta

Participants continued to receive commercially available epoetin alfa or beta by intravenous or subcutaneous injection, at the same starting dose, frequency and route of administration as received during the last week of the Screening Period, with the first study dose of epoetin alfa or beta administered after randomization at Week 0.

The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.

Intervention Type: DRUG

Other Intervention Names

Omontys; Hematide; AF37702 Injection; Epogen; Neorecormon

Eligibility Criteria

Inclusion Criteria

1. Participants with chronic renal failure on hemodialysis for ≥ 3 months prior to randomization.

2. On IV epoetin alfa or beta maintenance therapy continuously prescribed for a minimum of 8 weeks prior to randomization.

3. Four consecutive hemoglobin values with a mean ≥ 10.0 and ≤ 12.0 g/dL during the Screening Period.

Exclusion Criteria

1. Females who are pregnant or breast-feeding.

2. Known intolerance to any erythropoiesis stimulating agent or pegylated molecule or to all parenteral iron supplementation products.

3. Known bleeding or coagulation disorder.

4. Known hematologic disease or cause of anemia other than renal disease

5. Poorly controlled hypertension.

6. Evidence of active malignancy within one year prior to randomization.

7. Temporary (untunneled) dialysis access catheter.

8. A scheduled kidney transplant.

9. A scheduled surgery that may be expected to lead to significant blood loss.

• 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

Hot Springs, Arkansas, United States

Research Facility

McGehee, Arkansas, United States

Research Facility

Pine Bluff, Arkansas, United States

Research Facility

Bakersfield, California, United States

Research Facility

Glendale, California, United States

Research Facility

Los Angeles, California, United States

Research Facility

Los Angeles, California, United States

Research Facility

Los Angeles, California, United States

Research Facility

Riverside, California, United States

Research Facility

Simi Valley, California, United States

Research Facility

Whittier, California, United States

Research Facility

Yuba City, California, United States

Research Facility

Westminster, Colorado, United States

Research Facility

Lauderdale Lakes, Florida, United States

Research Facility

Miami, Florida, United States

Research Facility

Pinecrest, Florida, United States

Research Facility

Flossmoor, Illinois, United States

Research Facility

Hines, Illinois, United States

Research Facility

Louisville, Kentucky, 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

Brookhaven, Mississippi, United States

Research Facility

Brooklyn, New York, United States

Research Facility

Flushing, New York, United States

Research Facility

The Bronx, New York, United States

Research Facility

Asheville, North Carolina, United States

Research Facility

Toledo, Ohio, United States

Research Facility

Oklahoma City, Oklahoma, United States

Research Facility

Erie, Pennsylvania, United States

Research Facility

Philadelphia, Pennsylvania, United States

Research Facility

Providence, Rhode Island, United States

Research Facility

Orangeburg, South Carolina, United States

Research Facility

Arlington, Texas, United States

Research Facility

Houston, Texas, United States

Research Facility

San Antonio, Texas, United States

Research Facility

Fairfax, Virginia, United States

Research Facility

Burgas, , Bulgaria

Research Facility

Pazardzhik, , Bulgaria

Research Facility

Pleven, , Bulgaria

Research Facility

Plovdiv, , Bulgaria

Research Facility

Plovdiv, , Bulgaria

Research Facility

Rousse, , Bulgaria

Research Facility

Sofia, , Bulgaria

Research Facilities (2)

Sofia, , Bulgaria

Research Facility

Sofia, , Bulgaria

Research Facility

Sofia, , Bulgaria

Research Facility

Varna, , Bulgaria

Research Facility

Veliko Tarnovo, , Bulgaria

Research Facility

Amiens, , France

Research Facility

Bordeaux, , France

Research Facility

Montpellier, , France

Research Facility

Vannes, , France

Research Facilities (2)

Bremen, , Germany

Research Facility

Franfurt, , Germany

Research Facility

Hamburg, , Germany

Research Facility

Kaiserslautern, , Germany

Research Facility

Como, , Italy

Research Facility

Cremona, , Italy

Research Facility

Lecco, , Italy

Research Facility

Modena, , Italy

Research Facility

Prato, , Italy

Research Facility

Ciechanów, , Poland

Research Facility

Katowice, , Poland

Research Facility

Pabianice, , Poland

Research Facility

Włocławek, , Poland

Research Facility

Bucharest, , Romania

Research Facility

Bucharest, , Romania

Research Facility

Iași, , Romania

Research Facility

Alicante, , Spain

Research Facility

Barcelona, , Spain

Research Facility

Barcelona, , Spain

Research Facility

Barcelona, , Spain

Research Facility

Ciudad Real, , Spain

Research Facility

Madrid, , Spain

Research Facility

Madrid, , Spain

Research Facility

Santander, , Spain

Research Facility

Carshalton, , United Kingdom

Research Facility

London, , United Kingdom

Research Facility

London, , United Kingdom

Research Facility

London, , United Kingdom

Research Facility

Swansea, , United Kingdom

Countries

United States; Bulgaria; France; Germany; Italy; Poland; Romania; Spain; United Kingdom

References

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: RESULT

PMID: 23343061 (View on PubMed)

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: DERIVED

PMID: 23343062 (View on PubMed)

Other Identifiers

2007-004153-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AFX01-14

Identifier Type: -

Identifier Source: org_study_id