A phase 3b, multicenter, open-label, single-arm study of roxadustat within a US dialysis organization: The DENALI study

IF 1.2 4区医学 Q3 UROLOGY & NEPHROLOGY

Hemodialysis International Pub Date : 2023-10-24 DOI:10.1111/hdi.13122

John Larkin, Jeffrey Hymes, Marcus L. Britton, Yemmie Oluwatosin, Jacqueline Nolen, Lixia Zhu, Arnold Silva

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引用次数: 0

Abstract

Introduction

Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved in several regions for the treatment of anemia of chronic kidney disease (CKD). DENALI, a phase 3b study, evaluated the efficacy, safety, and feasibility of roxadustat in patients with anemia of CKD receiving in-center or home dialysis.

Methods

Eligible patients received open-label roxadustat, dosed three times weekly for 24 weeks, with an optional extension of ≤1 year. Initial dosing depended on erythropoiesis-stimulating agent (ESA) dose at screening for patients receiving ESAs (≥6 weeks) and weight-based for those not (total <6 weeks). Primary efficacy endpoints were proportion of patients with mean hemoglobin (Hb) ≥10.0 g/dL averaged over Weeks 16–24, and mean Hb change from baseline to the average during Weeks 16–24. Treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) were assessed.

Findings

Of 281 patients screened, 203 were treated and 201 included in the full analysis set. Overall, 166 patients completed the 24-week treatment period and 126 continued into the extension period. Mean baseline Hb was 10.4 g/dL and 82.6% received in-center hemodialysis. Overall, 84.6% of patients achieved a mean Hb ≥ 10.0 g/dL averaged Weeks 16–24. Mean (standard deviation) Hb change from baseline averaged Weeks 16–24 was 0.5 (1.0) g/dL. Prespecified subgroup analyses were consistent with primary analyses. Dosing adherence was 94%. Overall, 3.0% of patients received a red blood cell transfusion at up to Week 24. TEAEs and TESAEs were reported by 71.4% and 25.6% of patients, respectively. The most frequently reported TESAEs were COVID-19 (n = 5; 2.5%), and acute myocardial infarction, pneumonia, and sepsis (each n = 4; 2.0%).

Discussion

Roxadustat effectively achieved and/or maintained mean Hb levels ≥10.0 g/dL in patients receiving dialysis. The feasibility of incorporating oral roxadustat into dialysis organizations was successfully demonstrated with high dosing adherence. No new safety signals were identified.

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在美国透析组织中进行的一项多中心、开放标签、单臂的3b期罗沙司他研究:DENALI研究。

简介：罗沙司他是一种口服缺氧诱导因子脯氨酰羟化酶抑制剂，已在多个地区获得批准，用于治疗慢性肾脏疾病（CKD）贫血。DENALI是一项3b期研究，评估了罗沙司他在接受中心或家庭透析的CKD贫血患者中的疗效、安全性和可行性。方法：符合条件的患者接受开放标签罗沙司他，每周给药3次，共24次周，可选择延长≤1 年首次给药取决于接受ESA（≥6）的患者筛查时的红细胞生成刺激剂（ESA）剂量周）和基于体重的未筛查患者（总发现：在281名筛查患者中，203人接受了治疗，201人被纳入完整的分析集。总体而言，166名患者完成了24周的治疗期，126人继续进入延长期。平均基线Hb为10.4 g/dL，82.6%接受中心血液透析。总体而言，84.6%的患者平均Hb ≥ 10 g/dL平均16-24周。16-24周平均Hb变化平均值为0.5（1.0） g/dL。预先指定的亚组分析与主要分析一致。给药依从性为94%。总体而言，3.0%的患者在第24周之前接受了红细胞输注。TEAE和TESAE分别有71.4%和25.6%的患者报告。最常报告的TESAE是新冠肺炎（n = 5.2.5%），以及急性心肌梗死、肺炎和败血症（每个n = 4.2.0%）。讨论：Roxadustat有效地达到和/或保持了平均Hb水平≥10.0 g/dL。将口服罗沙司他纳入透析组织的可行性已通过高剂量依从性成功证明。没有发现新的安全信号。

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来源期刊

Hemodialysis International UROLOGY & NEPHROLOGY-

CiteScore

2.50

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Hemodialysis International was originally an annual publication containing the Proceedings of the International Symposium on Hemodialysis held in conjunction with the Annual Dialysis Conference. Since 2003, Hemodialysis International is published quarterly and contains original papers on clinical and experimental topics related to dialysis in addition to the Annual Dialysis Conference supplement. This journal is a must-have for nephrologists, nurses, and technicians worldwide. Quarterly issues of Hemodialysis International are included with your membership to the International Society for Hemodialysis. The journal contains original articles, review articles, and commentary to keep readers completely updated in the field of hemodialysis. Edited by international and multidisciplinary experts, Hemodialysis International disseminates critical information in the field.