A Phase 2, Open-label, Multi-center, Sequential, Dose Finding Study of the Safety, Pharmacodynamics, and Pharmacokinetics of Peginesatide Administered Intravenously for the Maintenance Treatment of Anemia in Chronic Hemodialysis Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 165
- 试验地点
- 1
- 主要终点
- Average weekly hemoglobin and hemoglobin change from baseline
研究概览
简要总结
The purpose of this study is to evaluate the safety, pharmacodynamics (PD), and pharmacokinetics (PK) of multiple intravenous doses of peginesatide in participants with chronic kidney disease (CKD) who are on hemodialysis.
详细描述
This was a Phase 2, multicenter, open-label, sequential, dose-finding trial designed with up to 12 treatment cohorts of 15 participants per cohort. Each participant received an intravenous dose of peginesatide administered once every 4 weeks (Q4W) for a total of 6 doses. Dosage regimens varied by cohort. Participants were followed for a minimum of 42 days after the last administration of peginesatide.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Participant is informed of the investigational nature of this study and has given written, witnessed informed consent in accordance with institutional, local, and national guidelines;
- •Males or females ≥ 18 years of age. Pre-menopausal females (with the exception of those who are surgically sterile) must have a negative pregnancy test at screening; those who are sexually active must practice a highly effective method of birth control for at least 4 weeks prior to study start, and must be willing to continue contraception until at least 4 weeks after the last dose of study drug. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence (only acceptable if practiced as a life-style and not acceptable if one who is sexually active practices abstinence only for the duration of the study) or vasectomized partner;
- •Clinically stable on hemodialysis for ≥6 months prior to study drug administration;
- •Urea clearance/volume (Kt/V) ≥ 1.2 within the 4 weeks prior to study drug administration;
- •Epoetin alfa maintenance therapy of ≥ 60 and ≤ 375 U/kg/wk continuously prescribed for 8 weeks prior to study drug administration. In the last 3 weeks prior to study drug administration, variation in prescribed total weekly dose must be ≤ 25% from the mean of the last three prescribed total weekly doses;
- •Three mid- or end-of-week hemoglobin values of ≥ 10.0 and ≤ 12.5 g/dL in the 3 weeks prior to study drug administration with ≤ 1.2 g/dL difference between the three values;
- •One serum ferritin level ≥ 100 micrograms per liter (μg/L) or one transferrin saturation ≥ 20% or one reticulocyte hemoglobin content (CHr) ≥ 29 picograms within 4 weeks prior to study drug administration;
- •One serum folate level above the lower limit of normal during the 4 weeks prior to study drug administration;
- •One vitamin B12 level above the lower limit of normal during the 4 weeks prior to study drug administration;
- •Weight ≥ 45 kilograms (kg) within the 4 weeks prior to study drug administration;
- •One white blood cell count ≥ 3.0 x 10^9/L within 4 weeks prior to study drug administration; and
- •One platelet count ≥ 100 x 10^9/L and ≤ 500 x 10^9/L within 4 weeks prior to study drug administration.
排除标准
- •Known intolerance to erythropoiesis stimulating agents;
- •History of antibodies to erythropoiesis stimulating agents or history of pure red cell aplasia;
- •Known intolerance to parenteral iron supplementation;
- •Red blood cell transfusion within 12 weeks prior to study drug administration;
- •Hemoglobinopathy (e.g., homozygous sickle-cell disease, thalassemia of all types, etc.);
- •Known hemolysis;
- •Chronic, uncontrolled, or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.);
- •C-reactive protein greater than 30 mg/L within the 4 weeks prior to study drug administration;
- •Moderate or significant infection within 2 weeks prior to study drug administration;
- •Known coagulation disorder based on clinical context and laboratory [activated partial thromboplastin time (aPTT) or international normalized ratio (INR)] results;
- •Temporary (untunneled) dialysis access catheter;
- •Uncontrolled or symptomatic secondary hyperparathyroidism;
- •Poorly controlled hypertension within the 4 weeks prior to study drug administration, per the Investigator's clinical judgment (e.g., systolic ≥ 170 mm Hg or diastolic ≥ 100 mm Hg on repeat readings);
- •Any history of multiple significant drug allergies;
- •History of severe or unstable reactive airway disease within the previous 10 years;
- •Epileptic seizure in the 6 months prior to screening;
- •Chronic congestive heart failure (New York Heart Association Class IV);
- •High likelihood of early withdrawal or interruption of the study (e.g., myocardial infarction, severe or unstable coronary artery disease, stroke, respiratory, autoimmune, neuropsychiatric, or neurological abnormalities, liver disease including active hepatitis B or C, active HIV disease, or any other clinically significant medical disease or conditions in the prior 6 months that may, in the Investigator's opinion, interfere with assessment or follow-up of the patient);
- •Evidence of malignancy within the past 5 years (except non-melanoma skin cancer which is not an exclusion criterion);
- •Life expectancy < 12 months;
- •Anticipated elective surgery during the study period; and
- •Previous exposure to any investigational agent within 6 weeks prior to administration of study drug or planned receipt during the study period.
研究组 & 干预措施
Cohorts 4 and 9
Conversion from epoetin alfa to peginesatide with a CF of 0.050: peginesatide dose administered intravenously Q4W for a total of 6 doses. With transition period between epoetin treatment and start of peginesatide treatment.
干预措施: peginesatide (Drug)
Cohort 1
Conversion from epoetin alfa to peginesatide with a conversion factor (CF) of 0.033: peginesatide dose administered intravenously once every 4 weeks (Q4W) for a total of up to 6 doses. No transition period between epoetin treatment and start of peginesatide treatment.
干预措施: peginesatide (Drug)
Cohort 2
Conversion from epoetin alfa to peginesatide with a CF of 0.041: peginesatide dose administered intravenously Q4W for a total of 6 doses. No transition period between epoetin treatment and start of peginesatide treatment.
干预措施: peginesatide (Drug)
Cohort 3
Conversion from epoetin alfa to peginesatide with a CF of 0.050: peginesatide dose administered intravenously Q4W for a total of 6 doses. No transition period between epoetin treatment and start of peginesatide treatment.
干预措施: peginesatide (Drug)
Cohort 5
Conversion from epoetin alfa to peginesatide with a CF of 0.066: peginesatide dose administered intravenously Q4W for a total of 6 doses. With transition period between epoetin treatment and start of peginesatide treatment.
干预措施: peginesatide (Drug)
Cohort 6
Conversion from epoetin alfa to peginesatide with tiered peginesatide starting doses of 0.05, 0.075, 0.1 or 0.15 mg/kg based on total weekly doses of epoetin alfa . Doses were administered intravenously Q4W for a total of 6 doses. With transition period between epoetin treatment and start of peginesatide treatment.
干预措施: peginesatide (Drug)
Cohorts 7 and 8
Conversion from epoetin alfa to peginesatide with tiered peginesatide starting doses of 0.05, 0.075, 0.1 or 0.15 mg/kg based on total weekly doses of epoetin alfa dose. Doses were administered intravenously Q4W for a total of 6 doses. No transition period between epoetin treatment and start of peginesatide treatment.
干预措施: peginesatide (Drug)
Cohorts 10 and 11
Conversion from epoetin alfa to peginesatide with fixed peginesatide starting doses of 4, 6, 12 or 16 mg based on total weekly doses of epoetin alfa. Doses were administered intravenously Q4W for a total of 6 doses. No transition period between epoetin treatment and start of peginesatide treatment.
干预措施: peginesatide (Drug)
结局指标
主要结局
Average weekly hemoglobin and hemoglobin change from baseline
时间窗: Baseline to Week 27
次要结局
- Percentage of participants with hemoglobin within 1.0 gram per deciliter (g/dL) above or below baseline(Baseline to Week 25)
- Percentage of participants who maintain hemoglobin within 9.5-13.0 g/dL(Baseline to Week 25)
- Percentage of participants who maintain hemoglobin within 11.0-13.0 g/dL(Baseline to Week 25)