Clinical trial NCT00598273: Safety & Efficacy of Peginesatide for the Treatment of Anemia in Participants With Chronic Renal Failure Not on Dialysis
Official title: AFX01-11: 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: 490
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 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

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 Receive 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: Montgomery
country: United States
facility: Research Facility
state: Alabama
city: Tempe
country: United States
facility: Research Facility
state: Arizona
city: Hot Springs
country: United States
facility: Research Facility
state: Arkansas
city: Bakersfield
country: United States
facility: Research Facility
state: California
city: Chula Vista
country: United States
facility: Research Facility
state: California
city: Glendale
country: United States
facility: Research Facility
state: California
city: Huntington Beach
country: United States
facility: Research Facility
state: California
city: Los Angeles
country: United States
facility: Research Facility
state: California
city: Orange
country: United States
facility: Research Facility
state: California
city: Paramount
country: United States
facility: Research Facility
state: California
city: Pasadena
country: United States
facility: Research Facility
state: California
city: Riverside
country: United States
facility: Research Facility
state: California
city: San Dimas
country: United States
facility: Research Facility
state: California
city: Stanford
country: United States
facility: Research Facility
state: California
city: Whittier
country: United States
facility: Research Facility
state: California
city: Whittier
country: United States
facility: Research Facility
state: California
city: Yuba City
country: United States
facility: Research Facility
state: California
city: Thornton
country: United States
facility: Research Facility
state: Colorado
city: Washington
country: United States
facility: Research Facility
state: District of Columbia
city: Holly Hill
country: United States
facility: Research Facility
state: Florida
city: Hudson
country: United States
facility: Research Facility
state: Florida
city: Miami
country: United States
facility: Research Facility
state: Florida
city: Ocala
country: United States
facility: Research Facility
state: Florida
city: Orlando
country: United States
facility: Research Facility
state: Florida
city: Tampa
country: United States
facility: Research Facility
state: Florida
city: Augusta
country: United States
facility: Research Facility
state: Georgia
city: Honolulu
country: United States
facility: Research Facility
state: Hawaii
city: Chicago
country: United States
facility: Research Facility
state: Illinois
city: Evergreen Park
country: United States
facility: Research Facility
state: Illinois
city: Hines
country: United States
facility: Research Facility
state: Illinois
city: Evansville
country: United States
facility: Research Facility
state: Indiana
city: Lafayette
country: United States
facility: Research Facility
state: Indiana
city: Wichita
country: United States
facility: Research Facility
state: Kansas
city: Shreveport
country: United States
facility: Research Facility
state: Louisiana
city: Bethesda
country: United States
facility: Research Facility
state: Maryland
city: Fall River
country: United States
facility: Research Facility
state: Massachusetts
city: Worcester
country: United States
facility: Research Facility
state: Massachusetts
city: Midland
country: United States
facility: Research Facility
state: Michigan
city: Columbus
country: United States
facility: Research Facility
state: Mississippi
city: Kansas City
country: United States
facility: Research Facility
state: Missouri
city: Northfield
country: United States
facility: Research Facility
state: New Jersey
city: Toms River
country: United States
facility: Research Facility
state: New Jersey
city: Binghamton
country: United States
facility: Research Facility
state: New York
city: Great Neck
country: United States
facility: Research Facility
state: New York
city: Mineola
country: United States
facility: Research Facility
state: New York
city: Charlotte
country: United States
facility: Research Facility
state: North Carolina
city: Oklahoma City
country: United States
facility: Research Facility
state: Oklahoma
city: Bend
country: United States
facility: Research Facility
state: Oregon
city: Portland
country: United States
facility: Research Facility
state: Oregon
city: Allentown
country: United States
facility: Research Facility
state: Pennsylvania
city: Erie
country: United States
facility: Research Facility
state: Pennsylvania
city: Johnstown
country: United States
facility: Research Facility
state: Pennsylvania
city: Providence
country: United States
facility: Research Facility
state: Rhode Island
city: Orangeburg
country: United States
facility: Research Facility
state: South Carolina
city: Rock Hill
country: United States
facility: Research Facility
state: South Carolina
city: Clarksville
country: United States
facility: Research Facility
state: Tennessee
city: Knoxville
country: United States
facility: Research Facility
state: Tennessee
city: Nashville
country: United States
facility: Research Facility
state: Tennessee
city: Austin
country: United States
facility: Research Facility
state: Texas
city: Corpus Christi
country: United States
facility: Research Facility
state: Texas
city: Corsicana
country: United States
facility: Research Facility
state: Texas
city: Edinburg
country: United States
facility: Research Facility
state: Texas
city: Houston
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: San Antonio
country: United States
facility: Research Facility
state: Texas
city: Salem
country: United States
facility: Research Facility
state: Virginia
city: Bluefield
country: United States
facility: Research Facility
state: West Virginia
city: Caguas
country: Puerto Rico
facility: Research Facility
city: Ponce
country: Puerto Rico
facility: Research Facility
city: San Juan
country: Puerto Rico
facility: Research Facility
city: San Juan
country: Puerto Rico
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.