Safety & Efficacy of Peginesatide for the Treatment of Anemia in Participants With Chronic Renal Failure Not on Dialysis

Anemia Clinical Trial

— PEARL 1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00598273
• Other study ID #: AFX01-11
• Status: Completed
• Phase: Phase 3
• First received: January 10, 2008
• Last updated: February 6, 2013
• Start date: October 2007
• Est. completion date: February 2010

Study information

• Verified date: February 2013
• Source: Affymax
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 490
• Est. completion date: February 2010
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Chronic Kidney Disease
• Chronic Renal Failure
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• peginesatide
Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.025 milligram per kilogram (mg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).
• peginesatide
Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.04 mg/kg and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
• Darbepoetin alfa
As prescribed, starting dose of 0.75 microgram per kilogram (mcg/kg) administered by subcutaneous injection once every 2 weeks. The dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Affymax	Takeda

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

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 d — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change in Hemoglobin Between Baseline and the Evaluation Period	The baseline hemoglobin value is defined as the mean of three hemoglobin values: the two most recent hemoglobin values taken prior to the day of randomization and the value obtained on the day of randomization. The mean hemoglobin during the Evaluation Period for each participant is calculated as the mean of the available hemoglobin values during Study Weeks 25 through 36.	Baseline and Weeks 25-36	No
Secondary	Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Correction and Evaluation Periods		Weeks 0 to 36	No
Secondary	Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods.	A hemoglobin response is defined as hemoglobin increase of = 1.0 gram per deciliter (g/dL) above baseline and a hemoglobin = 11.0 g/dL without RBC transfusion during the previous 8 weeks.	Weeks 0 to 36	No

External Links

•   FDA Briefing Document for the Oncologic Drugs Advisory Committee (ODAC) - December 7, 2011 for peginesatide injection