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.

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Anemia

Intervention / Treatment
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* Drug: Peginesatide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient was a man or woman 18 to 90 years of age, inclusive. The patient had CKD and met 1 of the following criteria: Had been on dialysis for ≥6 months prior to enrollment, or Had not yet begun dialysis (hemodialysis or peritoneal dialysis) and was not anticipated to require initiation of dialysis during participation in the study. The patient was on stable darbepoetin alfa maintenance therapy (either SC or IV) continuously for a minimum of 8 weeks prior to enrollment. 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: The patient had known bleeding or coagulation disorder. 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). 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). The patient had advanced chronic CKD defined by New York Heart Association Class III or IV. The patient had a known history of seizure disorder or received antiepileptic medication for a seizure disorder within 6 months prior to enrollment. The patient had a scheduled kidney transplant. Patients currently on a transplant waiting list were not excluded, unless there was an identified donor.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peginesatide<br> | Drug: Peginesatide<br>* 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.<br>* Other names: Omontys;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Hemoglobin Between Baseline and the Evaluation Period | Mean change in Hemoglobin between Baseline (the mean of the 4 most recent hemoglobin values prior to enrollment and the hemoglobin on the day of enrollment) and the Evaluation Period (mean hemoglobin from Weeks 19 to 24). | Baseline and Week 19 to Week 24. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hemoglobin Within the Target Range of 10.0 to 12.0 g/dL During the Evaluation Period | Mean hemoglobin was calculated from measurements taken during the Evaluation Period from Week 19 to Week 24. The target hemoglobin range was between 10.0 to 12.0 g/dL. The 95% confidence interval was calculated from the normal approximation with continuity correction. | Week 19 to Week 24 | 
| Percentage of Participants With a Change in Hemoglobin From Baseline to the Evaluation Period Within 1 g/dL | Percentage of participants with a mean change in hemoglobin between Baseline (the mean of the 4 most recent hemoglobin values prior to enrollment and the hemoglobin on the day of enrollment) and the Evaluation Period (mean hemoglobin measured at Weeks 19 to 24) of less than or equal ± 1 g/dL. The 95% confidence interval was calculated from the normal approximation with continuity correction. | Baseline and Week 19 to Week 24. | 
| Percentage of Participants With Red Blood Cell Transfusions | The percentage of participants who received one or more red blood cell transfusions, including packed red blood cells and whole blood transfusions, during the Titration Period (Weeks 0 - 18) and Evaluation Period (Weeks 19 -24). 95% Confidence Intervals were calculated from the normal approximation with continuity correction. | Up to 24 weeks. | 
| Mean Hemoglobin During 4-week Intervals | Hemoglobin was measured every 2 weeks during the Titration Period (Weeks 0-18) and weekly during the Evaluation Period (Weeks 19-24). | Up to 24 weeks. | 
| Percentage of Participants With Target Hemoglobin of 10.0 to 12.0 g/dL by 4-week Intervals. | Percentage of participants with mean hemoglobin levels falling between the target level of 10.0 to 12.0 g/dL during 4-week study intervals. Hemoglobin was measured every 2 weeks during the Titration Period (Weeks 0-18) and weekly during the Evaluation Period (Weeks 19-24). 95% Confidence Intervals were calculated from the normal approximation with continuity correction. | Up to 24 weeks. | 
| Percentage of Participants With Dose Adjustments During the Study | The peginesatide dose was adjusted to maintain Hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline during the Titration Period (Weeks 0-18) and Evaluation Period (Weeks 19-24). A dose was classified as adjusted if it was not within 20% of the previous dose. A dose was classified as increased or decreased if it was >20% higher or >20% lower respectively, than the previous dose. | From Week 4 to Week 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anemia, Drug Therapy, Hemodialysis, Kidney Failure