A Phase 3, Randomized, Double-Blind, Placebo Controlled Study of the Efficacy and Safety of Roxadustat for the Treatment of Anemia in Chronic Kidney Disease Patients Not on Dialysis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 594
- 试验地点
- 138
- 主要终点
- Percentage of Participants With a Hemoglobin (Hb) Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy Prior to Hb Response
研究概览
简要总结
This study was conducted to treat anemia in patients with chronic kidney disease. Anemia is a reduced number of red blood cells or hemoglobin. Hemoglobin is important for the transport of oxygen in your blood. The purpose of the study was to see if Roxadustat is both effective and safe as a treatment for anemia in patients with chronic kidney disease.
详细描述
The study consisted of three study periods as follows:
- Screening period: up to 6 weeks
- Treatment period: minimum 52 weeks (primary treatment period) up to a maximum of 104 weeks (extended treatment period)
- Post-Treatment Follow-Up period: 4 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Roxadustat
Participants received roxadustat according to the tiered weight-based approach, with starting doses of 70 mg given thrice weekly (TIW) to participants weighing up to 70 kg and 100 mg given TIW to participants weighing more than 70 kg. Dose-titration was performed based upon regular measurement of Hb levels until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL. Participants received roxadustat for at least 52 weeks up to a maximum of 104 weeks.
干预措施: Roxadustat (Drug)
Placebo
Participants received matching placebo according to the tiered weight-based approach, with starting doses of 70 mg given thrice weekly (TIW) to participants weighing up to 70 kg and 100 mg given TIW to participants weighing more than 70 kg. Dose-titration was performed based upon regular measurement of Hb levels until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL. Participants received matching placebo for at least 52 weeks up to a maximum of 104 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With a Hemoglobin (Hb) Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy Prior to Hb Response
时间窗: Baseline to week 24
Hemoglobin (Hb) response was measured as Yes or No. Response Yes (responders) was defined as: Hb ≥11.0 g/dL and Hb increase from baseline by ≥ 1.0 g/dL, for participants with baseline Hb \> 8.0 g/dL; or Hb increase from baseline by ≥ 2.0 g/dL, for participants with baseline Hb ≤ 8.0 g/dL at two consecutive visits with available data separated at least 5 days during the first 24 weeks of treatment without having received rescue therapy (red blood cell (RBC) transfusion, erythropoiesis-stimulating agent (ESA), or intravenous (IV) iron prior to Hb response. This was the primary efficacy endpoint for EU (EMA).
Hb Change From Baseline (BL) to the Average Hb in Weeks 28-52 Regardless of Rescue Therapy
时间窗: Baseline and weeks 28 to 52
The change from baseline to the average Hb values across weeks 28 to 52 without having received rescue therapy. The Hb values from visit windows at weeks 28, 32, 36, 40, 44, 48 and 52 were used for the calculation of the average of weeks 28 to 52. This was the primary efficacy endpoint for US (FDA).
次要结局
- Change From BL in Mean Arterial Pressure (MAP) to the Average MAP of Weeks 20 to 28(Baseline and weeks 20 to 28)
- Hb Change From BL to the Average Hb in Weeks 28-36 Without Having Received Rescue Therapy Within 6 Weeks Prior to and During 8-Week Evaluation Period(Baseline and weeks 28 to 36)
- Change From BL in Low-Density Lipoprotein (LDL) Cholesterol (Regardless of Fasting Status) to the Average LDL Cholesterol of Weeks 12 to 28(Baseline and weeks 12 to 28)
- Time to First Use of Rescue Therapy (Composite of Red Blood Cell (RBC) Transfusions, Erythropoiesis-stimulating Agent (ESA) Use, and Intravenous (IV) Iron)(Baseline to week 104 (End of Treatment [EOT]))
- Change From BL in Short Form (SF)-36 Vitality (VT) Sub-score to the Average VT Sub-score of Weeks 12 to 28(Baseline and weeks 12 to 28)
- Change From BL in SF-36 Physical Functioning (PF) Sub-score to the Average PF Sub-score of Weeks 12 to 28(Baseline and weeks 12 to 28)
- Time to First Occurrence of Hypertension(Baseline and year 0.5, year 1, year 1.5 and year 2)
- Rate of Progression of CKD Measured by Annualized Estimated Glomerular Filtration Rate (eGFR) Slope Over Time(Baseline to week 108)
- Average Level of Hb Over Weeks 28 to 36 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period(Weeks 28 to 36)
- Average Level of Hb Over Weeks 44 to 52 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period(Weeks 44 to 52)
- Average Level of Hb Over Weeks 96 to 104 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period(Weeks 96 to 104)
- Time to Achieve the First Hb Response Without Rescue Therapy, as Defined by Primary Endpoint(Baseline to week 24)
- Hb Change From BL to Each Post-Dosing Time Point(Baseline (day 1) and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104)
- Hb Change From BL to the Average Hb Value of Weeks 28-36 Regardless of the Use of Rescue Therapy(Baseline and weeks 28 to 36)
- Hb Change From BL to the Average Hb Value of Weeks 44-52 Regardless of the Use of Rescue Therapy(Baseline and weeks 44 to 52)
- Hb Change From BL to the Average Hb Value of Weeks 96-104 Regardless of the Use of Rescue Therapy(Baseline and weeks 96 to 104)
- Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 28-36 Without Use of Rescue Therapy(Baseline and weeks 28 to 36)
- Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 44-52 Without Use of Rescue Therapy(Baseline and weeks 44 to 52)
- Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 96-104 Without Use of Rescue Therapy(Baseline and weeks 96 to 104)
- Change From BL to the Average Value of Weeks 12-28 in Quality of Life (QoL) SF-36 Physical Component Score (PCS)(Baseline and weeks 12 to 28)
- Time to First Hospitalization(Baseline to week 104)
- Number of Days of Hospitalization Per Patient Exposure Year (PEY)(Baseline to week 104)
- Time to First Use of Rescue Therapy (Composite of RBC, Transfusions, ESA Use, and IV Iron) in the First 24 Weeks of Treatment(Baseline to week 24)
- Time to First Use of RBC Transfusions(Baseline to week 104)
- Mean Monthly Number of RBC Packs(Baseline to week 104)
- Mean Monthly Volume of Blood Transfused(Baseline to week 104)
- Time to First Use of ESA Rescue Therapy(Baseline to week 104)
- Time to First Use of IV Iron(Baseline to week 104)
- Change From BL to Each Post-Dosing Visit in Total Cholesterol(Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104)
- Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio(Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104)
- Percentage of Participants Who Have Achieved Antihypertensive Treatment Goal in CKD Participants Over Weeks 12-28(Weeks 12 to 28)
- Change From BL to the Average Value of Weeks 12-28 in Anemia Subscale (Ans) of Functional Assessment of Cancer Therapy (FACT-An) Score(Baseline and weeks 12 to 28)
- Change From BL to the Average Value of Weeks 12-28 in Total FACT-An Score(Baseline and weeks 12 to 28)
- Change From BL to the Average Value of Weeks 12-28 in the Euroqol Questionnaire - 5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score(Baseline and weeks 12 to 28)
- Change From BL to the Average Value of Weeks 12-28 in Overall Work Impairment Due to Anaemic Symptoms(Baseline and weeks 12 to 28)
- Percentage of Participants in Each Category in Patients' Global Impression of Change (PGIC)(Week 12 to 28)
- Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol(Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104)
- Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1)(Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104)
- Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB)(Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104)
- Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1(Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104)
- Percentage of Participants With Mean LDL Cholesterol <100 mg/dL Calculated Over Weeks 12 to 28(Weeks 12 to 28)
- Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio(Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104)
- Change From BL to Each Study Visit in Serum Hepcidin(Baseline and weeks 4,12,20,36,52,104)
- Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT)(Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104)
- Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine(Baseline and weeks 12, 24, 36, 52, 64, 76, 88, 104)
- Time to CKD Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death)(Baseline and year 0.5, year 1, year 1.5 and year 2)
- Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant(Baseline and year 0.5, year 1, year 1.5 and year 2)
- Change From BL to Each Study Visit in Serum Ferritin(Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104)
- Change From BL to Each Study Visit in Serum HbA1c Level(Baseline and weeks 12, 28, 36, 44, 60, 84, 104)
- Change From BL to Each Study Visit in Fasting Blood Glucose(Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104)
- Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline(Baseline and year 0.5, year 1, year 1.5 and year 2)