Phase 3, Randomized, Open-label, Active-controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Maintenance Treatment of Anemia in Subjects With Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD) (PRO2TECT-CONVERSION)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,725
- 试验地点
- 4
- 主要终点
- Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)
研究概览
简要总结
A multicenter, randomized, open-label, active-controlled Phase 3 study for the maintenance treatment of anemia in participants with Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD)
详细描述
This is a multicenter, randomized, open-label, active-controlled Phase 3 study of the efficacy and safety of Vadadustat versus Darbepoetin alfa for the maintenance treatment of anemia in participants with NDD-CKD
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
Sponsor was blinded during the 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
- •≥18 years of age
- •Diagnosis of chronic kidney disease (CKD) with an estimated glomerular filtration rate ≤60 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) at Screening and not expected to start dialysis within 6 months of Screening
- •Currently maintained on erythropoiesis-stimulating agents therapy, with a dose received within 6 weeks prior to or during Screening
- •Mean Screening hemoglobin between 8.0 and 11.0 grams per deciliter (g/dL) (inclusive) in the United States (US) and between 9.0 and 12.0 g/dL (inclusive) outside of the US
- •Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening
排除标准
- •Anemia due to a cause other than CKD or participant with active bleeding or recent blood loss
- •Red blood cell transfusion within 8 weeks prior to randomization
- •Uncontrolled hypertension
- •Severe heart failure at Screening (New York Heart Association Class IV)
- •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, or stroke within 12 weeks prior to or during Screening
- •Hypersensitivity to Darbepoetin or Vadadustat or to any of their excipients
研究组 & 干预措施
Vadadustat
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 Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)
时间窗: Baseline; Weeks 24 to 36
The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline hemoglobin concentration (\<10.0 versus ≥10.0 g/dL), geographic region (United States \[US\] versus European Union \[EU\] versus Rest of World \[ROW\]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 \[no CHF\] or I versus II or III) as covariates.
Median Time to First Major Adverse Cardiovascular Event (MACE)
时间窗: Up to Week 208
MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.
次要结局
- Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis(Up to Week 208)
- Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)(Baseline; Weeks 40 to 52)
- Median Time to First Cardiovascular MACE(Up to Week 208)
- Median Time to First Cardiovascular Death(Up to Week 208)
- Median Time to First All-cause Mortality(Up to Week 208)