Phase 3b, Randomized, Open-label, Active-controlled Trial Evaluating the Efficacy and Safety of Oral Vadadustat Once Daily (QD) and Three Times Weekly (TIW) for the Maintenance Treatment of Anemia in Hemodialysis Subjects Converting From Erythropoiesis-Stimulating Agents (ESAs)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 319
- 试验地点
- 2
- 主要终点
- Change From Baseline in Hb to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26)
研究概览
简要总结
This trial will be conducted to demonstrate the efficacy and safety of vadadustat compared to darbepoetin alfa for the maintenance treatment of anemia in hemodialysis participants after conversion from current erythropoiesis-stimulating agent (ESA) therapy.
详细描述
This study consists of three periods:
- Screening Period
- Conversion and Maintenance Treatment Period
- Safety Follow-up Period
Individual participants will participate in total trial duration of approximately 64 weeks.
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
盲法说明
This is an open-label, Sponsor-blind study.
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
- •Receiving chronic, outpatient three times weekly (TIW) in-center hemodialysis for end-stage renal disease for at least 12 weeks prior to Screening
- •Hemodialysis adequacy as indicated by single-pool Kt/Vurea ≥ 1.2 using the most recent historical measurement within 8 weeks prior to or during Screening
- •Use of any approved erythropoiesis-stimulating agents (ESAs) for at least the 8 weeks prior to Screening Visit 2
- •Two hemoglobin (Hb) values, at least 4 days apart, measured by the central laboratory during Screening within the following prespecified ranges:
- •Hb values between 8.0 and 11.0 grams per deciliter (g/dL) (inclusive) in the United States;
- •Hb values between 9.0 and 12.0 g/dL (inclusive) in Europe
- •Serum ferritin ≥ 100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥ 20% during Screening
- •Folate and vitamin B12 measurements ≥ lower limit of normal during Screening
排除标准
- •Anemia due to a cause other than chronic kidney disease (e.g., sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia)
- •Participants meeting cut-off of the following equivalent mean weekly doses calculated over 8 weeks prior to Screening Visit 2
- •Methoxy polyethylene glycol-epoetin beta > 50 micrograms (µg)/week;
- •Darbepoetin alfa > 100 µg/week;
- •Epoetin analogues > 23000 International Units (IU)/week
- •Active bleeding or recent blood loss within 8 weeks prior to randomization
- •Red blood cell transfusion within 8 weeks prior to randomization
- •Current uncontrolled hypertension.
- •Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), surgical or percutaneous intervention for coronary, cerebrovascular or peripheral artery disease (aortic or lower extremity), surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for heart failure (HF) or New York Heart Association Class IV HF, or stroke within 12 weeks prior to or during Screening.
- •Known hypersensitivity to vadadustat, darbepoetin alfa, or any of their excipients
研究组 & 干预措施
Vadadustat once daily (QD)
干预措施: Vadadustat (Drug)
Vadadustat three times weekly (TIW)
干预措施: Vadadustat (Drug)
Darbepoetin alfa
干预措施: Darbepoetin alfa (Drug)
结局指标
主要结局
Change From Baseline in Hb to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26)
时间窗: Baseline; Weeks 20 to 26
The Baseline Hb was defined as the average of the last 2 central laboratory Hb values taken on or prior to the first dose date. The average for the PEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 20 through 26, regardless of intercurrent events. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as PEP value minus the Baseline value.
次要结局
- Change From Baseline in Hb to the Average Over the Secondary Evaluation Period (SEP) (Weeks 46 to 52)(Baseline; Weeks 46 to 52)