Clinical trial NCT00598442: Safety and Efficacy of Peginesatide for the Treatment of Anemia in Participants With Chronic Renal Failure Not on Dialysis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Renal Failure
Chronic Kidney Disease
Anemia
Keywords: 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
Lead sponsor: Affymax
Sponsor class: INDUSTRY
Collaborators: name: Takeda
First posted: 2008-01-21
Enrollment: 493
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Mean Change in Hemoglobin Between Baseline and the Evaluation Period
timeFrame: Baseline and Weeks 25-36
Secondary outcomes:
measure: Proportion of Participants Who Received Red Blood Cell (RBC) Transfusions During the Correction and Evaluation Periods
timeFrame: Weeks 0 to 36
measure: Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods
timeFrame: Weeks 0 to 36
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Facility
state: Arizona
city: Fayetteville
country: United States
facility: Research Facility
state: Arkansas
city: Fountain Valley
country: United States
facility: Research Facility
state: California
city: Fullerton
country: United States
facility: Research Facility
state: California
city: Granada Hills
country: United States
facility: Research Facility
state: California
city: Los Angeles
country: United States
facility: Research Facility
state: California
city: San Diego
country: United States
facility: Research Facility
state: California
city: Whittier
country: United States
facility: Research Facility
state: California
city: Lauderdale Lakes
country: United States
facility: Research Facility
state: Florida
city: Pembroke Pines
country: United States
facility: Research Facility
state: Florida
city: Pinecrest
country: United States
facility: Research Facility
state: Florida
city: Canton
country: United States
facility: Research Facility
state: Georgia
city: Columbus
country: United States
facility: Research Facility
state: Georgia
city: Marietta
country: United States
facility: Research Facility
state: Georgia
city: Caldwell
country: United States
facility: Research Facility
state: Idaho
city: Meridian
country: United States
facility: Research Facility
state: Idaho
city: Chicago
country: United States
facility: Research Facility
state: Illinois
city: Mishawaka
country: United States
facility: Research Facility
state: Indiana
city: Ames
country: United States
facility: Research Facility
state: Iowa
city: Baton Rouge
country: United States
facility: Research Facility
state: Louisiana
city: Lafayette
country: United States
facility: Research Facility
state: Louisiana
city: Rockville
country: United States
facility: Research Facility
state: Maryland
city: Springfield
country: United States
facility: Research Facility
state: Massachusetts
city: Detroit
country: United States
facility: Research Facility
state: Michigan
city: Detroit
country: United States
facility: Research Facility
state: Michigan
city: Flint
country: United States
facility: Research Facility
state: Michigan
city: Petoskey
country: United States
facility: Research Facility
state: Michigan
city: Troy
country: United States
facility: Research Facility
state: Michigan
city: Washington
country: United States
facility: Research Facility
state: Missouri
city: Flushing
country: United States
facility: Research Facility
state: New York
city: Williamsville
country: United States
facility: Research Facility
state: New York
city: Asheville
country: United States
facility: Research Facility
state: North Carolina
city: Columbus
country: United States
facility: Research Facility
state: Ohio
city: Bend
country: United States
facility: Research Facility
state: Oregon
city: Arlington
country: United States
facility: Research Facility
state: Texas
city: Houston
country: United States
facility: Research Facility
state: Texas
city: San Antonio
country: United States
facility: Research Facility
state: Texas
city: Burlington
country: United States
facility: Research Facility
state: Vermont
city: Fairfax
country: United States
facility: Research Facility
state: Virginia
city: Tacoma
country: United States
facility: Research Facility
state: Washington
city: Morgantown
country: United States
facility: Research Facility
state: West Virginia
city: Neenah
country: United States
facility: Research Facility
state: Wisconsin
city: Sofia
country: Bulgaria
facility: Research Facility
city: Sofia
country: Bulgaria
facility: Research Facility
city: Varna
country: Bulgaria
facility: Research Facility
city: Veliko Tarnovo
country: Bulgaria
facility: Research Facility
city: Prague
country: Czech Republic
facility: Research Facility
city: Tabor
country: Czech Republic
facility: Research Facility
city: Zdar nad Sazavou
country: Czech Republic
facility: Research Facility
city: Demmin
country: Germany
facility: Research Facility
city: Balatonfured
country: Hungary
facility: Research Facility
city: Kistarcsa
country: Hungary
facility: Research Facility
city: Szigetvar
country: Hungary
facility: Research Facility
city: Lecco
country: Italy
facility: Research Facility
city: Pavia
country: Italy
facility: Research Facility
city: Bialystok
country: Poland
facility: Research Facility
city: Gdansk
country: Poland
facility: Research Facility
city: Katowice
country: Poland
facility: Research Facility
city: Zamosc
country: Poland
facility: Research Facility
city: Ponce
country: Puerto Rico
facility: Research Facility
city: Iasi
country: Romania
facility: Research Facility
city: Oradea
country: Romania
facility: Research Facility
city: Timisoara
country: Romania
facility: Research Facility
city: London
country: United Kingdom
facility: Research Facility
Study officials:
affiliation: Affymax
name: Vice President, Clinical Development
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.