AFX01-13: 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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 493
- 试验地点
- 1
- 主要终点
- Mean Change in Hemoglobin Between Baseline and the Evaluation Period
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic renal failure with an estimated glomerular filtration rate < 60 milliliters per minute per 1.73 m^2 and not expected to begin dialysis for at least 12 weeks.
- •Two consecutive hemoglobin values ≥ 8.0 g/dL and < 11.0 g/dL within 4 weeks prior to randomization.
排除标准
- •Females who are pregnant or breast-feeding.
- •Treatment with an ESA in the 12 weeks prior to randomization.
- •Known intolerance to any ESA, parenteral iron supplementation, or pegylated molecule.
- •Prior chronic hemodialysis or chronic peritoneal dialysis treatment.
- •Known bleeding or coagulation disorder.
- •Known hematologic disease or cause of anemia other than renal disease.
- •Poorly controlled hypertension.
- •Evidence of active malignancy within one year prior to randomization
- •A scheduled kidney transplant.
研究组 & 干预措施
Peginesatide 0.025 mg/kg
干预措施: peginesatide (Drug)
Peginesatide 0.04 mg/kg
干预措施: peginesatide (Drug)
Darbepoetin alfa
干预措施: Darbepoetin alfa (Drug)
结局指标
主要结局
Mean Change in Hemoglobin Between Baseline and the Evaluation Period
时间窗: Baseline and Weeks 25-36
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.
次要结局
- Proportion of Participants Who Received 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(Weeks 0 to 36)