Safety & Efficacy of Peginesatide for Treatment of Anemia in Participants on Dialysis Not Receiving an ESA

AFX01-15: A Phase 2, 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) Undergoing Hemodialysis and Not on Erythropoiesis Stimulating Agent (ESA) Treatment

The purpose of this study is to evaluate the safety and efficacy of peginesatide for the treatment of anemia in participants with chronic kidney disease who are on dialysis and are not taking any treatment to increase their red blood cell production.

Study Overview

• Status: Completed
• Conditions: Anemia; Chronic Kidney Disease; Chronic Renal Failure
• Intervention / Treatment: Drug: peginesatide; Drug: peginesatide; Drug: Epoetin 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 (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 equal proportions to two peginesatide treatment regimens, in which participants received peginesatide once every 4 weeks, and one control, epoetin alfa, treatment regimen, in which participants received epoetin alfa three times per week. Total commitment time of this study was a 4 week screening period followed by a minimum of 7 months of treatment.

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Irkutsk, Russian Federation
    • Research Facility
  • Krasnodar, Russian Federation
    • Research Facility
  • Krasnoyarsk, Russian Federation
    • Research Facility
  • Moscow, Russian Federation
    • Research Facility
  • Nizhniy Novgorod, Russian Federation
    • Research Facility
  • Omsk, Russian Federation
    • Research Facility
  • Petrozavodsk, Russian Federation
    • Research Facility
  • Saratov, Russian Federation
    • Research Facility
  • St. Petersburg, Russian Federation
    • Research Facility
  • Tver, Russian Federation
    • Research Facility
  • Volzhsk, Russian Federation
    • 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. On hemodialysis for chronic renal failure for at least 2 weeks prior to randomization.
2. Two consecutive hemoglobin values of ≥ 8.0 g/dL and < 11.0 g/dL within the 4 weeks prior to randomization.

Exclusion Criteria

1. Females who are pregnant or breast-feeding.
2. Prior treatment with an erythropoiesis stimulating agent (ESA) in the 12 weeks prior to randomization.
3. Known intolerance to any ESA, parenteral iron supplementation, or pegylated molecule.
4. Known bleeding or coagulation disorder.
5. Known hematologic disease or cause for anemia other than renal disease
6. Poorly controlled hypertension.
7. Evidence of active malignancy within one year.
8. 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
Experimental: Peginesatide 0.04 mg/kg	Drug: peginesatide; Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.04 milligram per kilogram (mg/kg); the dose 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 intravenous injection once every 4 weeks at the starting dose of 0.08 mg/kg; the dose 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 0.08 mg/kg	Drug: peginesatide; Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.04 milligram per kilogram (mg/kg); the dose 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 intravenous injection once every 4 weeks at the starting dose of 0.08 mg/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.; Other Names: Omontys; Hematide; AF37702 Injection
Active Comparator: Epoetin Alfa	Drug: Epoetin Alfa; Participants received Epoetin alfa by intravenous injection three times a week at the starting dose of 50 Units/kg. The dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.; Other Names: Eprex

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 the two most recent hemoglobin values taken prior to the day of randomization plus the value obtained on the day of randomization prior to Dose 1. The mean hemoglobin during the Evaluation period for each participant is calculated as the mean of the available hemoglobin values during Study Weeks 21 through 28.	Baseline and Weeks 21-28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Who Receive Red Blood Cell (RBC) or Whole Blood Transfusions During the Correction and Evaluation Periods		Weeks 1 to 28
Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods	A hemoglobin response is defined as a hemoglobin increase of ≥ 1.0 g/dL above baseline and a hemoglobin ≥ 11.0 g/dL without RBC or whole blood transfusion during the previous 8 weeks.	Weeks 1 to 28

Collaborators and Investigators

• Sponsor: Affymax
• Collaborators: Takeda

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: May 15, 2008
• First Submitted That Met QC Criteria: May 16, 2008
• First Posted (Estimate): May 19, 2008

Study Record Updates

• Last Update Posted (Estimate): June 29, 2012
• Last Update Submitted That Met QC Criteria: June 22, 2012
• Last Verified: June 1, 2012

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; Epoetin Alfa
• Other Study ID Numbers: AFX01-15