Clinical trial NCT00597584: Safety & Efficacy of Peginesatide for Maintenance Treatment of Anemia in Participants With Chronic Kidney Disease on Hemodialysis
Official title: AFX01-14: 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
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: 823
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 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.

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.

Primary outcomes:
measure: Mean Change in Hemoglobin Between Baseline and the Evaluation Period
timeFrame: Baseline to 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: Phoenix
country: United States
facility: Research Facility
state: Arizona
city: Hot Springs
country: United States
facility: Research Facility
state: Arkansas
city: McGehee
country: United States
facility: Research Facility
state: Arkansas
city: Pine Bluff
country: United States
facility: Research Facility
state: Arkansas
city: Bakersfield
country: United States
facility: Research Facility
state: California
city: Glendale
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: Riverside
country: United States
facility: Research Facility
state: California
city: Simi Valley
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: Westminster
country: United States
facility: Research Facility
state: Colorado
city: Lauderdale Lakes
country: United States
facility: Research Facility
state: Florida
city: Miami
country: United States
facility: Research Facility
state: Florida
city: Pinecrest
country: United States
facility: Research Facility
state: Florida
city: Flossmoor
country: United States
facility: Research Facility
state: Illinois
city: Hines
country: United States
facility: Research Facility
state: Illinois
city: Louisville
country: United States
facility: Research Facility
state: Kentucky
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: Brookhaven
country: United States
facility: Research Facility
state: Mississippi
city: Bronx
country: United States
facility: Research Facility
state: New York
city: Brooklyn
country: United States
facility: Research Facility
state: New York
city: Flushing
country: United States
facility: Research Facility
state: New York
city: Asheville
country: United States
facility: Research Facility
state: North Carolina
city: Toledo
country: United States
facility: Research Facility
state: Ohio
city: Oklahoma City
country: United States
facility: Research Facility
state: Oklahoma
city: Erie
country: United States
facility: Research Facility
state: Pennsylvania
city: Philadelphia
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: 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: Fairfax
country: United States
facility: Research Facility
state: Virginia
city: Burgas
country: Bulgaria
facility: Research Facility
city: Pazardzhik
country: Bulgaria
facility: Research Facility
city: Pleven
country: Bulgaria
facility: Research Facility
city: Plovdiv
country: Bulgaria
facility: Research Facility
city: Plovdiv
country: Bulgaria
facility: Research Facility
city: Rousse
country: Bulgaria
facility: Research Facility
city: Sofia
country: Bulgaria
facility: Research Facility
city: Sofia
country: Bulgaria
facility: Research Facilities (2)
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: Amiens Cedex 1
country: France
facility: Research Facility
city: Bordeaux
country: France
facility: Research Facility
city: Montpellier Cedex 5
country: France
facility: Research Facility
city: Vannes
country: France
facility: Research Facility
city: Bremen
country: Germany
facility: Research Facilities (2)
city: Franfurt
country: Germany
facility: Research Facility
city: Hamburg
country: Germany
facility: Research Facility
city: Kaiserslautern
country: Germany
facility: Research Facility
city: Como
country: Italy
facility: Research Facility
city: Cremona
country: Italy
facility: Research Facility
city: Lecco
country: Italy
facility: Research Facility
city: Modena
country: Italy
facility: Research Facility
city: Prato
country: Italy
facility: Research Facility
city: Ciechanow
country: Poland
facility: Research Facility
city: Katowice
country: Poland
facility: Research Facility
city: Pabianice
country: Poland
facility: Research Facility
city: Wloclawek
country: Poland
facility: Research Facility
city: Bucuresti
country: Romania
facility: Research Facility
city: Bucuresti
country: Romania
facility: Research Facility
city: Iasi
country: Romania
facility: Research Facility
city: Alicante
country: Spain
facility: Research Facility
city: Barcelona
country: Spain
facility: Research Facility
city: Barcelona
country: Spain
facility: Research Facility
city: Barcelona
country: Spain
facility: Research Facility
city: Ciudad Real
country: Spain
facility: Research Facility
city: Madrid
country: Spain
facility: Research Facility
city: Madrid
country: Spain
facility: Research Facility
city: Santander
country: Spain
facility: Research Facility
city: Carshalton
country: United Kingdom
facility: Research Facility
city: London
country: United Kingdom
facility: Research Facility
city: London
country: United Kingdom
facility: Research Facility
city: London
country: United Kingdom
facility: Research Facility
city: Swansea
country: United Kingdom
facility: Research Facility
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.