Clinical trial NCT00597753: Safety & Efficacy of Peginesatide for Maintenance Treatment of Anemia in Participants With Chronic Kidney Disease on Hemodialysis
Official title: AFX01-12: A Phase 3, Randomized, Active-controlled, Open-label, Multi-center Study of the Safety and Efficacy of Peginesatide for the Maintenance Treatment of Anemia in Hemodialysis Patients Previously Treated With Epoetin Alfa
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
dialysis
erythropoietin
EPO
erythropoiesis stimulating agent
ESA
Hematide™
hemodialysis
hemoglobin
Hb
Hgb
Omontys
peginesatide
red blood cell
red blood cell production
Lead sponsor: Affymax
Sponsor class: INDUSTRY
Collaborators: name: Takeda
First posted: 2008-01-18
Enrollment: 803
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 the 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 alfa 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, 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. Participants with chronic renal failure on hemodialysis for ≥ 3 months prior to randomization.
2. On intravenous epoetin alfa 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 (ESA) 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.

Primary outcomes:
measure: Mean Change in Hemoglobin Between Baseline and the Evaluation Period
timeFrame: Baseline and Weeks 29-36
Secondary outcomes:
measure: Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods
timeFrame: Weeks 0 to 36
measure: Proportion of Participants Whose Mean Hemoglobin Level During the Evaluation Period is Within the Target Range of 10.0 - 12.0 Grams Per Deciliter (g/dL)
timeFrame: Weeks 29 to 36
Other outcomes:
Locations:
city: Paragould
country: United States
facility: Research Facility
state: Arkansas
city: Fairfield
country: United States
facility: Research Facility
state: California
city: Granada Hills
country: United States
facility: Research Facility
state: California
city: Los Alamitos
country: United States
facility: Research Facility
state: California
city: Los Angeles
country: United States
facility: Research Facility
state: California
city: Los Angeles
country: United States
facility: Research Facility
state: California
city: Los Angeles
country: United States
facility: Research Facility
state: California
city: Lynwood
country: United States
facility: Research Facility
state: California
city: Monterey Park
country: United States
facility: Research Facility
state: California
city: Mountain View
country: United States
facility: Research Facility
state: California
city: Paramount
country: United States
facility: Research Facility
state: California
city: San Diego
country: United States
facility: Research Facilities (2)
state: California
city: San Dimas
country: United States
facility: Research Facility
state: California
city: Whittier
country: United States
facility: Research Facility
state: California
city: Denver
country: United States
facility: Research Facility
state: Colorado
city: Middlebury
country: United States
facility: Research Facility
state: Connecticut
city: Hudson
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: Orlando
country: United States
facility: Research Facility
state: Florida
city: Pembroke Pines
country: United States
facility: Research Facility
state: Florida
city: Augusta
country: United States
facility: Research Facility
state: Georgia
city: Augusta
country: United States
facility: Research Facility
state: Georgia
city: Decatur
country: United States
facility: Research Facility
state: Georgia
city: Marietta
country: United States
facility: Research Facility
state: Georgia
city: Honolulu
country: United States
facility: Research Facility
state: Hawaii
city: Boise
country: United States
facility: Research Facility
state: Idaho
city: Chicago
country: United States
facility: Research Facility
state: Illinois
city: Evergreen Park
country: United States
facility: Research Facility
state: Illinois
city: Gurnee
country: United States
facility: Research Facility
state: Illinois
city: Peoria
country: United States
facility: Research Facility
state: Illinois
city: Evansville
country: United States
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state: Indiana
city: Wichita
country: United States
facility: Research Facility
state: Kansas
city: Lexington
country: United States
facility: Research Facility
state: Kentucky
city: Baton Rouge
country: United States
facility: Research Facility
state: Louisiana
city: Lafayette
country: United States
facility: Research Facility
state: Louisiana
city: New Orleans
country: United States
facility: Research Facility
state: Louisiana
city: Shreveport
country: United States
facility: Research Facility
state: Louisiana
city: Bethesda
country: United States
facility: Research Facility
state: Maryland
city: Rockville
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: Dearborn
country: United States
facility: Research Facility
state: Michigan
city: Kalamazoo
country: United States
facility: Research Facility
state: Michigan
city: Columbus
country: United States
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state: Mississippi
city: Tupelo
country: United States
facility: Research Facility
state: Mississippi
city: St. Louis
country: United States
facility: Research Facility
state: Missouri
city: Las Vegas
country: United States
facility: Research Facility
state: Nevada
city: Eatontown
country: United States
facility: Research Facility
state: New Jersey
city: Bronx
country: United States
facility: Research Facility
state: New York
city: Bronx
country: United States
facility: Research Facility
state: New York
city: Brooklyn
country: United States
facility: Research Facility
state: New York
city: New York
country: United States
facility: Research Facility
state: New York
city: Williamsville
country: United States
facility: Research Facility
state: New York
city: Yonkers
country: United States
facility: Research Facility
state: New York
city: Durham
country: United States
facility: Research Facility
state: North Carolina
city: Raleigh
country: United States
facility: Research Facility
state: North Carolina
city: Canton
country: United States
facility: Research Facility
state: Ohio
city: Cincinnati
country: United States
facility: Research Facility
state: Ohio
city: Columbus
country: United States
facility: Research Facility
state: Ohio
city: Roseburg
country: United States
facility: Research Facility
state: Oregon
city: Allentown
country: United States
facility: Research Facility
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Facility
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Facility
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Facility
state: Pennsylvania
city: Greenville
country: United States
facility: Research Facilities (2)
state: South Carolina
city: Sumter
country: United States
facility: Research Facility
state: South Carolina
city: Dyersburg
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: Arlington
country: United States
facility: Research Facility
state: Texas
city: Fort Worth
country: United States
facility: Research Facility
state: Texas
city: Fort Worth
country: United States
facility: Research Facility
state: Texas
city: Fort Worth
country: United States
facility: Research Facility
state: Texas
city: Grand Prairie
country: United States
facility: Research Facility
state: Texas
city: Houston
country: United States
facility: Research Facilities (2)
state: Texas
city: Houston
country: United States
facility: Research Facility
state: Texas
city: McAllen
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: Tyler
country: United States
facility: Research Facility
state: Texas
city: Alexandria
country: United States
facility: Research Facility
state: Virginia
city: Chesapeake
country: United States
facility: Research Facility
state: Virginia
city: Fairfax
country: United States
facility: Research Facility
state: Virginia
city: Mechanicsville
country: United States
facility: Research Facility
state: Virginia
city: Norfolk
country: United States
facility: Research Facilities (2)
state: Virginia
city: Morgantown
country: United States
facility: Research Facility
state: West Virginia
city: Appleton
country: United States
facility: Research Facility
state: Wisconsin
city: Oshkosh
country: United States
facility: Research Facility
state: Wisconsin
Study officials:
affiliation: Affymax
name: Vice President, Clinical Development
role: STUDY_DIRECTOR
References:
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.
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.