Safety & Efficacy of Peginesatide for the Treatment of Anemia in Participants With Chronic Renal Failure Not on Dialysis (PEARL 1)

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

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.

Study Overview

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

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 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.

• Study Type: Interventional
• Enrollment (Actual): 490
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Caguas, Puerto Rico, 00725
    • Research Facility
  • Ponce, Puerto Rico, 00716
    • Research Facility
  • San Juan, Puerto Rico, 00909
    • Research Facility
  • San Juan, Puerto Rico, 00918
    • Research Facility
• United States
  • Alabama
    • Montgomery, Alabama, United States, 36106
      • Research Facility
  • Arizona
    • Tempe, Arizona, United States, 85306
      • Research Facility
  • Arkansas
    • Hot Springs, Arkansas, United States, 71901
      • Research Facility
  • California
    • Bakersfield, California, United States, 93309
      • Research Facility
    • Chula Vista, California, United States, 91910
      • Research Facility
    • Glendale, California, United States, 91204
      • Research Facility
    • Huntington Beach, California, United States, 92646
      • Research Facility
    • Los Angeles, California, United States, 90095
      • Research Facility
    • Orange, California, United States, 92868
      • Research Facility
    • Paramount, California, United States, 90723
      • Research Facility
    • Pasadena, California, United States, 91106
      • Research Facility
    • Riverside, California, United States, 92505
      • Research Facility
    • San Dimas, California, United States, 91773
      • Research Facility
    • Stanford, California, United States, 94305-6203
      • Research Facility
    • Whittier, California, United States, 90603
      • Research Facility
    • Whittier, California, United States, 90606
      • Research Facility
    • Yuba City, California, United States, 95991
      • Research Facility
  • Colorado
    • Thornton, Colorado, United States, 80031
      • Research Facility
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Research Facility
  • Florida
    • Holly Hill, Florida, United States, 32117
      • Research Facility
    • Hudson, Florida, United States, 34667
      • Research Facility
    • Miami, Florida, United States, 33173
      • Research Facility
    • Ocala, Florida, United States, 34471
      • Research Facility
    • Orlando, Florida, United States, 32804
      • Research Facility
    • Tampa, Florida, United States, 33614
      • Research Facility
  • Georgia
    • Augusta, Georgia, United States, 30901
      • Research Facility
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Research Facility
  • Illinois
    • Chicago, Illinois, United States, 60616
      • Research Facility
    • Evergreen Park, Illinois, United States, 60805
      • Research Facility
    • Hines, Illinois, United States, 60141
      • Research Facility
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Research Facility
    • Lafayette, Indiana, United States, 47904
      • Research Facility
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Research Facility
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Research Facility
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • Research Facility
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Research Facility
    • Worcester, Massachusetts, United States, 01608
      • Research Facility
  • Michigan
    • Midland, Michigan, United States, 48640
      • Research Facility
  • Mississippi
    • Columbus, Mississippi, United States, 39705
      • Research Facility
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Research Facility
  • New Jersey
    • Northfield, New Jersey, United States, 08225
      • Research Facility
    • Toms River, New Jersey, United States, 08755
      • Research Facility
  • New York
    • Binghamton, New York, United States, 13903
      • Research Facility
    • Great Neck, New York, United States, 11021
      • Research Facility
    • Mineola, New York, United States, 11501
      • Research Facility
  • North Carolina
    • Charlotte, North Carolina, United States, 28208
      • Research Facility
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Research Facility
  • Oregon
    • Bend, Oregon, United States, 97701
      • Research Facility
    • Portland, Oregon, United States, 97210
      • Research Facility
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Research Facility
    • Erie, Pennsylvania, United States, 16507
      • Research Facility
    • Johnstown, Pennsylvania, United States, 15905
      • Research Facility
  • Rhode Island
    • Providence, Rhode Island, United States, 02904
      • Research Facility
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • Research Facility
    • Rock Hill, South Carolina, United States, 29732
      • Research Facility
  • Tennessee
    • Clarksville, Tennessee, United States, 37043
      • Research Facility
    • Knoxville, Tennessee, United States, 37923
      • Research Facility
    • Nashville, Tennessee, United States, 37205
      • Research Facility
  • Texas
    • Austin, Texas, United States, 78705
      • Research Facility
    • Corpus Christi, Texas, United States, 78404
      • Research Facility
    • Corsicana, Texas, United States, 75110
      • Research Facility
    • Edinburg, Texas, United States, 78539
      • Research Facility
    • Houston, Texas, United States, 77030
      • Research Facility
    • Houston, Texas, United States, 77099
      • Research Facility
    • San Antonio, Texas, United States, 78215
      • Research Facility
    • San Antonio, Texas, United States, 78229
      • Research Facility
  • Virginia
    • Salem, Virginia, United States, 24153
      • Research Facility
  • West Virginia
    • Bluefield, West Virginia, United States, 24701
      • 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. 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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Darbepoetin Alfa	Drug: 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.; Other Names: Aranesp
Experimental: Peginesatide 0.025 mg/kg	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).; Other Names: Omontys; Hematide; AF37702 Injection; Drug: 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.; Other Names: Omontys; Hematide; AF37702 Injection
Experimental: Peginesatide 0.04 mg/kg	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).; Other Names: Omontys; Hematide; AF37702 Injection; Drug: 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.; Other Names: Omontys; Hematide; AF37702 Injection

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 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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Affymax
• Collaborators: Takeda

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: January 10, 2008
• First Submitted That Met QC Criteria: January 18, 2008
• First Posted (Estimate): January 21, 2008

Study Record Updates

• Last Update Posted (Estimate): February 12, 2013
• Last Update Submitted That Met QC Criteria: February 6, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: hemoglobin; anemia; chronic kidney disease; erythropoiesis stimulating agent; CKD; CRF; Hgb; erythropoietin; 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; Darbepoetin alfa
• Other Study ID Numbers: AFX01-11