一项评估罗沙司他间歇口服给药治疗未接受透析的非透析慢性肾脏病且对红细胞生成刺激剂初治的日本贫血患者的 3 期、多中心、随机、双盲、开放性研究
A Phase 3, Multicenter, Randomized, Two-Arm, Open-Label Study of Intermittent Oral Dosing of Roxadustat for the Treatment of Anemia in Japanese Erythropoiesis-Stimulating Agent-Naïve Chronic Kidney Disease Patients Not on Dialysis.
机构信息
Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Data Science, Development, Astellas Pharma, Inc., Tokyo, Japan.
出版信息
Nephron. 2020;144(8):372-382. doi: 10.1159/000508100. Epub 2020 Jun 24.
INTRODUCTION
Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved for the treatment of anemia in Japan for patients with dialysis-dependent (DD) chronic kidney disease (CKD).
OBJECTIVE
Multicenter, randomized, open-label, noncomparative, phase 3 study to evaluate roxadustat for anemia of non-dialysis-dependent (NDD) CKD in Japan.
METHODS
Erythropoiesis stimulating agent (ESA)-naïve NDD-CKD patients were randomized to roxadustat (initial dose, 50 or 70 mg 3 times weekly), titrated to maintain hemoglobin (Hb) within 10.0-12.0 g/dL, for ≤24 weeks. Patients with either transferrin saturation of ≥5% or serum ferritin of ≥30 ng/mL during the screening period were eligible. Endpoints included response rate (proportion of patients achieving Hb ≥10.0 or ≥10.5 g/dL and Hb increase ≥1.0 g/dL from baseline) at end of treatment; average Hb (weeks 18-24); change of average Hb from baseline to weeks 18-24; maintenance rate (proportion of patients achieving Hb 10.0-12.0 g/dL at weeks 18-24); rate of rise (RoR) of Hb from weeks 0-4, discontinuation, or dose adjustment. Adverse events were monitored throughout the study.
RESULTS
Of 135 patients who provided informed consent, 100 were randomized and 99 received roxadustat (50 mg, n = 49; 70 mg, n = 50). The mean (SD) dose of roxadustat per intake at week 22 was 36.3 (22.7) mg in the roxadustat 50 mg group and 36.8 (16.0) mg in the roxadustat 70 mg group. Prior medications included oral iron therapy (20.2%) and intravenous iron therapy (1.0%). Overall response rate (95% CI) was 97.0% (91.4, 99.4; Hb ≥10.0 g/dL) and 94.9% (88.6, 98.3; Hb ≥10.5 g/dL). Mean (SD) Hb (weeks 18-24) was 11.17 (0.62) g/dL. Mean (SD) change of Hb from baseline (weeks 18-24) was 1.34 (0.86) g/dL. Maintenance rate (95% CI) was 88.8% (80.3, 94.5) among patients with ≥1 Hb measurement during weeks 18-24. Mean (SD) RoR of Hb was 0.291 (0.197) g/dL/week (50 mg) and 0.373 (0.235) g/dL/week (70 mg). Nasopharyngitis and hypertension were the most common adverse events.
CONCLUSION
Roxadustat increased and maintained Hb in ESA-naïve, partially iron-depleted NDD-CKD patients with anemia.
简介
罗沙司他是一种口服低氧诱导因子脯氨酰羟化酶抑制剂，在日本被批准用于治疗透析依赖型（DD）慢性肾脏病（CKD）患者的贫血。
目的
多中心、随机、开放标签、非对照、3 期研究，旨在评估罗沙司他在日本非透析依赖型（NDD）CKD 患者中的贫血治疗作用。
方法
红细胞生成刺激剂（ESA）初治的 NDD-CKD 患者被随机分配至罗沙司他（初始剂量为每周 3 次 50 或 70mg）组，滴定剂量以维持血红蛋白（Hb）在 10.0-12.0g/dL 范围内，持续 24 周。筛选期转铁蛋白饱和度≥5%或血清铁蛋白≥30ng/mL 的患者有资格入组。主要终点包括治疗结束时的反应率（Hb≥10.0或≥10.5g/dL 且与基线相比 Hb 增加≥1.0g/dL 的患者比例）；平均 Hb（第 18-24 周）；从基线到第 18-24 周的平均 Hb 变化；第 18-24 周时维持 Hb 水平在 10.0-12.0g/dL 的患者比例；第 0-4 周、停药或剂量调整时的 Hb 上升率（RoR）。整个研究期间监测不良事件。
结果
在提供知情同意的 135 名患者中，有 100 名被随机分组，99 名接受了罗沙司他治疗（50mg 组 49 名，70mg 组 50 名）。第 22 周时，罗沙司他每次摄入的平均（SD）剂量为 36.3（22.7）mg 组和 36.8（16.0）mg 组。之前的药物治疗包括口服铁剂（20.2%）和静脉铁剂（1.0%）。总反应率（95%CI）为 97.0%（91.4，99.4；Hb≥10.0g/dL）和 94.9%（88.6，98.3；Hb≥10.5g/dL）。平均（SD）Hb（第 18-24 周）为 11.17（0.62）g/dL。平均（SD）Hb 从基线的变化（第 18-24 周）为 1.34（0.86）g/dL。在第 18-24 周有≥1 次 Hb 测量的患者中，维持 Hb 水平在 10.0-12.0g/dL 的比例为 88.8%（80.3，94.5）。平均（SD）Hb RoR 为 0.291（0.197）g/dL/周（50mg 组）和 0.373（0.235）g/dL/周（70mg 组）。最常见的不良事件是鼻咽炎和高血压。
结论
罗沙司他可增加和维持 ESA 初治、部分铁缺乏的 NDD-CKD 贫血患者的 Hb 水平。
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