Phase 3, Randomized, Open-Label, Active-Controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Correction or Maintenance Treatment of Anemia in Subjects With Incident Dialysis-Dependent Chronic Kidney Disease (DD-CKD) (INNO2VATE - CORRECTION/CONVERSION)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 369
- 试验地点
- 3
- 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 correction or maintenance treatment of anemia in participants with incident dialysis-dependent chronic kidney disease (DD-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 correction or maintenance treatment in participants with anemia secondary to chronic kidney disease who have recently initiated dialysis treatment for end-stage renal disease.
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
- •Initiated chronic maintenance dialysis (either peritoneal or hemodialysis) for end-stage kidney disease within 16 weeks prior to Screening
- •Mean Screening hemoglobin between 8.0 and <11.0 grams per deciliter (g/dL) (inclusive)
- •Serum ferritin ≥100 nanograms per deciliter (ng/mL) and TSAT ≥20% during Screening
排除标准
- •Anemia due to a cause other than chronic kidney disease or participants with active bleeding or recent blood loss
- •Red blood cells transfusion within 8 weeks prior to randomization
- •Anticipated to recover adequate kidney function to no longer require dialysis
- •Uncontrolled hypertension
- •Severe heart failure at Screening (New York Heart Association Class IV)
- •Acute coronary syndrome (hospitalization for unstable angina, 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 congestive heart failure; or stroke within 12 weeks prior to or during Screening.
- •Participants meeting the criteria of erythropoiesis-stimulating agent resistance within 8 weeks prior to or during Screening defined as follows
- •epoetin: > 7700 units/dose three times per week or >23,000 units per week
- •Darbepoetin alfa: >100 micrograms per week (mcg/week)
- •methoxy polyethylene glycol-epoetin beta: >100 micrograms (mcg) every other week or >200 mcg/month
- •Hypersensitivity to Vadadustat, Darbepoetin alfa or 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 (\<9.5 versus ≥9.5 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 176 weeks
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. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0016 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-0016 and AKB-6548-CI-0017 has been reported under section "Statistical Analysis 2" of this outcome measure.
次要结局
- 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 All-cause Mortality(Up to 176 weeks)
- Median Time to First Cardiovascular MACE(Up to 176 weeks)
- Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis(Up to 176 weeks)
- Median Time to First Cardiovascular Death(Up to 176 weeks)