Safety & Efficacy of Peginesatide for Maintenance Treatment of Anemia in Participants With Chronic Kidney Disease on Hemodialysis (EMERALD 2)

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

The purpose of this study was to evaluate the safety and efficacy of peginesatide in the maintenance treatment of anemia in participants on dialysis.

Study Overview

• Status: Completed
• Conditions: Anemia; Chronic Kidney Disease; Chronic Renal Failure
• Intervention / Treatment: Drug: peginesatide; Drug: Epoetin alfa or Epoetin beta

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.

• Study Type: Interventional
• Enrollment (Actual): 823
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Burgas, Bulgaria, 8000
    • Research Facility
  • Pazardzhik, Bulgaria, 4400
    • Research Facility
  • Pleven, Bulgaria, 5800
    • Research Facility
  • Plovdiv, Bulgaria, 4003
    • Research Facility
  • Plovdiv, Bulgaria, 4000
    • Research Facility
  • Rousse, Bulgaria, 7002
    • Research Facility
  • Sofia, Bulgaria, 1527
    • Research Facility
  • Sofia, Bulgaria, 1606
    • Research Facility
  • Sofia, Bulgaria, 1309
    • Research Facility
  • Sofia, Bulgaria, 1431
    • Research Facilities (2)
  • Varna, Bulgaria, 9010
    • Research Facility
  • Veliko Tarnovo, Bulgaria, 5000
    • Research Facility
• France
  • Amiens Cedex 1, France, 80054
    • Research Facility
  • Bordeaux, France, 33000
    • Research Facility
  • Montpellier Cedex 5, France, 34295
    • Research Facility
  • Vannes, France, 56017
    • Research Facility
• Germany
  • Bremen, Germany, 28359
    • Research Facilities (2)
  • Franfurt, Germany, 60528
    • Research Facility
  • Hamburg, Germany, 22297
    • Research Facility
  • Kaiserslautern, Germany, 67655
    • Research Facility
• Italy
  • Como, Italy, 22100
    • Research Facility
  • Cremona, Italy, 26100
    • Research Facility
  • Lecco, Italy, 23900
    • Research Facility
  • Modena, Italy, 41100
    • Research Facility
  • Prato, Italy, 59100
    • Research Facility
• Poland
  • Ciechanow, Poland, 06-400
    • Research Facility
  • Katowice, Poland, 40-027
    • Research Facility
  • Pabianice, Poland, 95-200
    • Research Facility
  • Wloclawek, Poland, 87-800
    • Research Facility
• Romania
  • Bucuresti, Romania, 014461
    • Research Facility
  • Bucuresti, Romania, 050098
    • Research Facility
  • Iasi, Romania, 700503
    • Research Facility
• Spain
  • Alicante, Spain, 03010
    • Research Facility
  • Barcelona, Spain, 08025
    • Research Facility
  • Barcelona, Spain, 08902
    • Research Facility
  • Barcelona, Spain, 08907
    • Research Facility
  • Ciudad Real, Spain, 13005
    • Research Facility
  • Madrid, Spain, 28041
    • Research Facility
  • Madrid, Spain, 28922
    • Research Facility
  • Santander, Spain, 39008
    • Research Facility
• United Kingdom
  • Carshalton, United Kingdom, SM5 1AA
    • Research Facility
  • London, United Kingdom, SE5 9RS
    • Research Facility
  • London, United Kingdom, E1 1BB
    • Research Facility
  • London, United Kingdom, SW17 0QT
    • Research Facility
  • Swansea, United Kingdom, SA6 6NL
    • Research Facility
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Research Facility
  • Arkansas
    • Hot Springs, Arkansas, United States, 71901
      • Research Facility
    • McGehee, Arkansas, United States, 71654
      • Research Facility
    • Pine Bluff, Arkansas, United States, 71603
      • Research Facility
  • California
    • Bakersfield, California, United States, 93309
      • Research Facility
    • Glendale, California, United States, 91205
      • Research Facility
    • Los Angeles, California, United States, 90033
      • Research Facility
    • Los Angeles, California, United States, 90048
      • Research Facility
    • Los Angeles, California, United States, 90073
      • Research Facility
    • Riverside, California, United States, 92505
      • Research Facility
    • Simi Valley, California, United States, 93065
      • Research Facility
    • Whittier, California, United States, 90602
      • Research Facility
    • Yuba City, California, United States, 95991
      • Research Facility
  • Colorado
    • Westminster, Colorado, United States, 80031
      • Research Facility
  • Florida
    • Lauderdale Lakes, Florida, United States, 33313
      • Research Facility
    • Miami, Florida, United States, 33173
      • Research Facility
    • Pinecrest, Florida, United States, 33156
      • Research Facility
  • Illinois
    • Flossmoor, Illinois, United States, 60422
      • Research Facility
    • Hines, Illinois, United States, 60141
      • Research Facility
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Research Facility
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Research Facility
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Research Facility
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Research Facility
    • Detroit, Michigan, United States, 48236
      • Research Facility
  • Mississippi
    • Brookhaven, Mississippi, United States, 39601
      • Research Facility
  • New York
    • Bronx, New York, United States, 10461
      • Research Facility
    • Brooklyn, New York, United States, 11238
      • Research Facility
    • Flushing, New York, United States, 11355
      • Research Facility
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Research Facility
  • Ohio
    • Toledo, Ohio, United States, 43606
      • Research Facility
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Research Facility
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Research Facility
    • Philadelphia, Pennsylvania, United States, 19141
      • Research Facility
  • Rhode Island
    • Providence, Rhode Island, United States, 02904
      • Research Facility
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • Research Facility
  • Texas
    • Arlington, Texas, United States, 76015
      • Research Facility
    • Houston, Texas, United States, 77099
      • Research Facility
    • San Antonio, Texas, United States, 78215
      • Research Facility
  • Virginia
    • Fairfax, Virginia, United States, 22033
      • Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Peginesatide	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.; Other Names: Omontys; Hematide; AF37702 Injection
Active Comparator: Epoetin	Drug: 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.; Other Names: Epogen; Neorecormon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods	Weeks 0 to 36
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

Collaborators and Investigators

• Sponsor: Affymax
• Collaborators: Takeda

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: January 10, 2008
• First Submitted That Met QC Criteria: January 17, 2008
• First Posted (Estimate): January 18, 2008

Study Record Updates

• Last Update Posted (Estimate): March 8, 2013
• Last Update Submitted That Met QC Criteria: March 6, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: hemoglobin; anemia; chronic kidney disease; erythropoiesis stimulating agent; dialysis; CKD; CRF; Hgb; erythropoietin; hemodialysis; chronic renal failure; EPO; ESA; Hematide™; Hb; Omontys; peginesatide; red blood cell; red blood cell production
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: AFX01-14; 2007-004153-28 (EudraCT Number)