Clinical trial NCT00752609: 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.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Keywords: Anemia
Drug Therapy
Hemodialysis
Kidney Failure
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Affymax
First posted: 2008-09-15
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Mean Change in Hemoglobin Between Baseline and the Evaluation Period
timeFrame: Baseline and Week 19 to Week 24.
Secondary outcomes:
measure: Percentage of Participants With Hemoglobin Within the Target Range of 10.0 to 12.0 g/dL During the Evaluation Period
timeFrame: Week 19 to Week 24
measure: Percentage of Participants With a Change in Hemoglobin From Baseline to the Evaluation Period Within 1 g/dL
timeFrame: Baseline and Week 19 to Week 24.
measure: Percentage of Participants With Red Blood Cell Transfusions
timeFrame: Up to 24 weeks.
measure: Mean Hemoglobin During 4-week Intervals
timeFrame: Up to 24 weeks.
measure: Percentage of Participants With Target Hemoglobin of 10.0 to 12.0 g/dL by 4-week Intervals.
timeFrame: Up to 24 weeks.
measure: Percentage of Participants With Dose Adjustments During the Study
timeFrame: From Week 4 to Week 20
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: Middlebury
country: United States
state: Connecticut
city: Lauderdale Lakes
country: United States
state: Florida
city: Shreveport
country: United States
state: Louisiana
city: Dearborn
country: United States
state: Michigan
city: Columbus
country: United States
state: Mississippi
city: Mineola
country: United States
state: New York
city: Arlington
country: United States
state: Texas
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: