Safety and Efficacy of Peginesatide Injection for the Maintenance of Anemia in Chronic Renal Failure Participants Who Are on Hemodialysis or Do Not Require Dialysis and Previously Treated With Darbepoetin Alfa.

A Phase 2 Study of the Safety and Efficacy of Hematide Injection for the Maintenance Treatment of Anemia in Subjects With Chronic Renal Failure Who Are on Hemodialysis or Do Not Require Dialysis and Previously Treated With Darbepoetin Alfa

Sponsors

Lead Sponsor: Takeda

Collaborator: Affymax

Source Takeda
Brief Summary

The purpose of this study is to determine the efficacy and safety of Peginesatide Injection for the maintenance of anemia in patients with chronic renal failure who are on hemodialysis or do not require dialysis and who were previously treated with Darbepoetin Alfa.

Detailed Description

Anemia, resulting primarily from insufficient production of erythropoietin to support erythropoiesis, is a common consequence of chronic renal failure. Both North America and Europe have established clinical practice guidelines for the treatment and hemoglobin targets in chronic renal failure/chronic kidney disease patients. These guidelines recommend the use of erythropoiesis-stimulating agents (ESAs). The benefits of ESA therapy include reduced fatigue, improved quality of life, decreased cardiovascular mortality risk and improved cardiovascular function. An increased risk of death and serious cardiovascular and thromboembolic events, including myocardial infarction, stroke, congestive heart failure, and hemodialysis graft occlusion have been observed in controlled clinical trials of ESAs when administered to target hemoglobin levels of ≥13.5 g/dL. The vast majority of patients receiving hemodialysis receive ESA therapy to treat their anemia and most patients begin ESA therapy prior to any requirement for dialysis.

Anemia of chronic renal failure is due to several factors, primarily the inability of the diseased kidneys to produce adequate amounts of endogenous erythropoietin. Ancillary factors also include the shortened lifespan of red blood cells, iron and other nutritional deficiencies, infection, and inflammation. The prevalence of anemia increases with progressive deterioration of renal function, and affects more than 90% of patients with chronic renal failure Stage 5 (End Stage Renal Disease). Anemia is associated with increased mortality, increased likelihood of hospitalization, reduced cognitive function and exercise capacity, increased left ventricular hypertrophy and heart failure. Treatment of anemia reduces morbidity and mortality risks and may improve quality of life.

Erythropoiesis stimulating agents have been established as a treatment for anemia in chronic renal failure participants, and have improved the management of anemia over alternatives such as transfusion. Peginesatide (hematide) is a parenteral formulation being developed for the correction of anemia in patients with chronic renal failure, and 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.

Participants in this study received variable doses of peginesatide injection once every four weeks. Total commitment time for this study was about 30 weeks.

Overall Status Completed
Start Date September 2008
Completion Date December 2009
Primary Completion Date December 2009
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Mean Change in Hemoglobin Between Baseline and the Evaluation Period Baseline and Week 19 to Week 24.
Secondary Outcome
Measure Time Frame
Percentage of Participants With Hemoglobin Within the Target Range of 10.0 to 12.0 g/dL During the Evaluation Period Week 19 to Week 24
Percentage of Participants With a Change in Hemoglobin From Baseline to the Evaluation Period Within 1 g/dL Baseline and Week 19 to Week 24.
Percentage of Participants With Red Blood Cell Transfusions Up to 24 weeks.
Mean Hemoglobin During 4-week Intervals Up to 24 weeks.
Percentage of Participants With Target Hemoglobin of 10.0 to 12.0 g/dL by 4-week Intervals. Up to 24 weeks.
Percentage of Participants With Dose Adjustments During the Study From Week 4 to Week 20
Enrollment 102
Condition
Intervention

Intervention Type: Drug

Intervention Name: Peginesatide

Description: Peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.

Arm Group Label: Peginesatide

Eligibility

Criteria:

Inclusion Criteria:

1. The patient was a man or woman 18 to 90 years of age, inclusive.

2. The patient had CKD and met 1 of the following criteria:

1. Had been on dialysis for ≥6 months prior to enrollment, or

2. Had not yet begun dialysis (hemodialysis or peritoneal dialysis) and was not anticipated to require initiation of dialysis during participation in the study.

3. The patient was on stable darbepoetin alfa maintenance therapy (either SC or IV) continuously for a minimum of 8 weeks prior to enrollment.

4. The patient had 4 consecutive Hb values with a mean ≥10.0 and ≤12.0 g/dL during screening period, with the difference between the mean of the first 2 consecutive Hb values and the mean of the last 2 consecutive values being ≤1.0 g/dL.

Exclusion Criteria:

1. The patient had known bleeding or coagulation disorder.

2. The patient had known hematologic disease or cause of anemia other than renal disease (i.e., pure red cell aplasia, homozygous sickle-cell disease, thalassemia, multiplemyeloma, hemolytic anemia, and myelodysplastic syndrome).

3. The patient had received a recent course of intensive iron replacement (i.e., more than 500 mg IV in the 28 days prior to enrollment).

4. The patient had advanced chronic CKD defined by New York Heart Association Class III or IV.

5. The patient had a known history of seizure disorder or received antiepileptic medication for a seizure disorder within 6 months prior to enrollment.

6. The patient had a scheduled kidney transplant. Patients currently on a transplant waiting list were not excluded, unless there was an identified donor.

Gender: All

Minimum Age: 18 Years

Maximum Age: 90 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Medical Director Study Director Takeda
Location
Facility:
| Los Angeles, California, United States
| Sacramento, California, United States
| San Diego, California, United States
| Middlebury, Connecticut, United States
| Lauderdale Lakes, Florida, United States
| Shreveport, Louisiana, United States
| Dearborn, Michigan, United States
| Columbus, Mississippi, United States
| Mineola, New York, United States
| Arlington, Texas, United States
Location Countries

United States

Verification Date

June 2012

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Peginesatide

Type: Experimental

Study Design Info

Allocation: Non-Randomized

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov