Safety & Efficacy of Peginesatide for Maintenance Treatment of Anemia in Participants With Chronic Kidney Disease on Hemodialysis

Anemia Clinical Trial

— EMERALD 2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00597584
• Other study ID #: AFX01-14
• Secondary ID: 2007-004153-28
• Status: Completed
• Phase: Phase 3
• First received: January 10, 2008
• Last updated: March 6, 2013
• Start date: October 2007
• Est. completion date: January 2010

Study information

• Verified date: March 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 committeeGermany: Federal Institute for Drugs and Medical DevicesGermany: Ethics CommissionItaly: 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 CommitteeFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Committee for the Protection of PersonnesSpain: Agencia Española de Medicamentos y Productos SanitariosSpain: Comité Ético de Investigación Clínica
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 823
• Est. completion date: January 2010
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

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 intravenous (IV) or subcutaneous (SC) injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa or beta dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa or beta dose. Participants who received epoetin alfa or beta IV at the time of screening received peginesatide IV during the study, and participants who received epoetin alfa or beta SC at the time of screening received peginesatide SC during the study. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.
• Epoetin alfa or Epoetin beta
Participants continued to receive commercially available epoetin alfa or beta by intravenous or subcutaneous injection, at the same starting dose, frequency and route of administration as received during the last week of the Screening Period, with the first study dose of epoetin alfa or beta administered after randomization at Week 0. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.

Locations

Country	Name	City	State
Bulgaria	Research Facility	Burgas
Bulgaria	Research Facility	Pazardzhik
Bulgaria	Research Facility	Pleven
Bulgaria	Research Facility	Plovdiv
Bulgaria	Research Facility	Plovdiv
Bulgaria	Research Facility	Rousse
Bulgaria	Research Facilities (2)	Sofia
Bulgaria	Research Facility	Sofia
Bulgaria	Research Facility	Sofia
Bulgaria	Research Facility	Sofia
Bulgaria	Research Facility	Varna
Bulgaria	Research Facility	Veliko Tarnovo
France	Research Facility	Amiens Cedex 1
France	Research Facility	Bordeaux
France	Research Facility	Montpellier Cedex 5
France	Research Facility	Vannes
Germany	Research Facilities (2)	Bremen
Germany	Research Facility	Franfurt
Germany	Research Facility	Hamburg
Germany	Research Facility	Kaiserslautern
Italy	Research Facility	Como
Italy	Research Facility	Cremona
Italy	Research Facility	Lecco
Italy	Research Facility	Modena
Italy	Research Facility	Prato
Poland	Research Facility	Ciechanow
Poland	Research Facility	Katowice
Poland	Research Facility	Pabianice
Poland	Research Facility	Wloclawek
Romania	Research Facility	Bucuresti
Romania	Research Facility	Bucuresti
Romania	Research Facility	Iasi
Spain	Research Facility	Alicante
Spain	Research Facility	Barcelona
Spain	Research Facility	Barcelona
Spain	Research Facility	Barcelona
Spain	Research Facility	Ciudad Real
Spain	Research Facility	Madrid
Spain	Research Facility	Madrid
Spain	Research Facility	Santander
United Kingdom	Research Facility	Carshalton
United Kingdom	Research Facility	London
United Kingdom	Research Facility	London
United Kingdom	Research Facility	London
United Kingdom	Research Facility	Swansea
United States	Research Facility	Arlington	Texas
United States	Research Facility	Asheville	North Carolina
United States	Research Facility	Bakersfield	California
United States	Research Facility	Bronx	New York
United States	Research Facility	Brookhaven	Mississippi
United States	Research Facility	Brooklyn	New York
United States	Research Facility	Detroit	Michigan
United States	Research Facility	Detroit	Michigan
United States	Research Facility	Erie	Pennsylvania
United States	Research Facility	Fairfax	Virginia
United States	Research Facility	Flossmoor	Illinois
United States	Research Facility	Flushing	New York
United States	Research Facility	Glendale	California
United States	Research Facility	Hines	Illinois
United States	Research Facility	Hot Springs	Arkansas
United States	Research Facility	Houston	Texas
United States	Research Facility	Lauderdale Lakes	Florida
United States	Research Facility	Los Angeles	California
United States	Research Facility	Los Angeles	California
United States	Research Facility	Los Angeles	California
United States	Research Facility	Louisville	Kentucky
United States	Research Facility	McGehee	Arkansas
United States	Research Facility	Miami	Florida
United States	Research Facility	Oklahoma City	Oklahoma
United States	Research Facility	Orangeburg	South Carolina
United States	Research Facility	Philadelphia	Pennsylvania
United States	Research Facility	Phoenix	Arizona
United States	Research Facility	Pine Bluff	Arkansas
United States	Research Facility	Pinecrest	Florida
United States	Research Facility	Providence	Rhode Island
United States	Research Facility	Riverside	California
United States	Research Facility	Rockville	Maryland
United States	Research Facility	San Antonio	Texas
United States	Research Facility	Simi Valley	California
United States	Research Facility	Springfield	Massachusetts
United States	Research Facility	Toledo	Ohio
United States	Research Facility	Westminster	Colorado
United States	Research Facility	Whittier	California
United States	Research Facility	Yuba City	California

Sponsors (2)

Lead Sponsor	Collaborator
Affymax	Takeda

Countries where clinical trial is conducted

United States,  Bulgaria,  France,  Germany,  Italy,  Poland,  Romania,  Spain,  United Kingdom, 

References & Publications (1)

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 Me — 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 five hemoglobin values: the four 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 29 through 36.	Baseline to Weeks 29-36	No
Secondary	Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods		Weeks 0 to 36	No
Secondary	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)		Weeks 29 to 36	No

External Links

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