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

Anemia Clinical Trial

— PEARL 2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00598442
• Other study ID #: AFX01-13
• Secondary ID: 2007-004146-32
• Status: Completed
• Phase: Phase 3
• First received: January 10, 2008
• Last updated: February 6, 2013
• Start date: November 2007
• Est. completion date: December 2009

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 BoardBulgaria: Bulgarian Drug AgencyBulgaria: Ethics committeeCzech Republic: State Institute for Drug ControlCzech Republic: Ethics CommitteeGermany: Federal Institute for Drugs and Medical DevicesGermany: Ethics CommissionHungary: National Institute of PharmacyHungary: Scientific and Medical Research Council Ethics CommitteeItaly: The Italian Medicines AgencyItaly: Ethics CommitteePoland: The Central Register of Clinical TrialsPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsPoland: Ethics CommitteeRomania: National Medicines AgencyRomania: Ethics CommitteeUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics Committee
• 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: 493
• Est. completion date: December 2009
• Est. primary completion date: July 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 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.

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
Participants received darbepoetin alfa by subcutaneous injection once every 2 weeks, as prescribed. The starting dose was 0.75 microgram per kilogram (mcg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.

Locations

Country	Name	City	State
Bulgaria	Research Facility	Sofia
Bulgaria	Research Facility	Sofia
Bulgaria	Research Facility	Varna
Bulgaria	Research Facility	Veliko Tarnovo
Czech Republic	Research Facility	Prague
Czech Republic	Research Facility	Tabor
Czech Republic	Research Facility	Zdar nad Sazavou
Germany	Research Facility	Demmin
Hungary	Research Facility	Balatonfured
Hungary	Research Facility	Kistarcsa
Hungary	Research Facility	Szigetvar
Italy	Research Facility	Lecco
Italy	Research Facility	Pavia
Poland	Research Facility	Bialystok
Poland	Research Facility	Gdansk
Poland	Research Facility	Katowice
Poland	Research Facility	Zamosc
Puerto Rico	Research Facility	Ponce
Romania	Research Facility	Iasi
Romania	Research Facility	Oradea
Romania	Research Facility	Timisoara
United Kingdom	Research Facility	London
United States	Research Facility	Ames	Iowa
United States	Research Facility	Arlington	Texas
United States	Research Facility	Asheville	North Carolina
United States	Research Facility	Baton Rouge	Louisiana
United States	Research Facility	Bend	Oregon
United States	Research Facility	Burlington	Vermont
United States	Research Facility	Caldwell	Idaho
United States	Research Facility	Canton	Georgia
United States	Research Facility	Chicago	Illinois
United States	Research Facility	Columbus	Georgia
United States	Research Facility	Columbus	Ohio
United States	Research Facility	Detroit	Michigan
United States	Research Facility	Detroit	Michigan
United States	Research Facility	Fairfax	Virginia
United States	Research Facility	Fayetteville	Arkansas
United States	Research Facility	Flint	Michigan
United States	Research Facility	Flushing	New York
United States	Research Facility	Fountain Valley	California
United States	Research Facility	Fullerton	California
United States	Research Facility	Granada Hills	California
United States	Research Facility	Houston	Texas
United States	Research Facility	Lafayette	Louisiana
United States	Research Facility	Lauderdale Lakes	Florida
United States	Research Facility	Los Angeles	California
United States	Research Facility	Marietta	Georgia
United States	Research Facility	Meridian	Idaho
United States	Research Facility	Mishawaka	Indiana
United States	Research Facility	Morgantown	West Virginia
United States	Research Facility	Neenah	Wisconsin
United States	Research Facility	Pembroke Pines	Florida
United States	Research Facility	Petoskey	Michigan
United States	Research Facility	Phoenix	Arizona
United States	Research Facility	Pinecrest	Florida
United States	Research Facility	Rockville	Maryland
United States	Research Facility	San Antonio	Texas
United States	Research Facility	San Diego	California
United States	Research Facility	Springfield	Massachusetts
United States	Research Facility	Tacoma	Washington
United States	Research Facility	Troy	Michigan
United States	Research Facility	Washington	Missouri
United States	Research Facility	Whittier	California
United States	Research Facility	Williamsville	New York

Sponsors (2)

Lead Sponsor	Collaborator
Affymax	Takeda

Countries where clinical trial is conducted

United States,  Bulgaria,  Czech Republic,  Germany,  Hungary,  Italy,  Poland,  Puerto Rico,  Romania,  United Kingdom, 

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 Received 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 a 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