A phase 3b, multicenter, open-label, single-arm study of roxadustat (ASPEN): Operational learnings within United States dialysis organizations

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2023-06-28 DOI:10.1111/hdi.13100

Steven Fishbane, Mark Vishnepolsky, Yemmie Oluwatosin, Jacqueline Nolen, Lixia Zhu, Kerry Cooper, Amy Young

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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). ASPEN evaluated the efficacy, safety, and feasibility of roxadustat in patients with anemia of CKD in US dialysis organizations.

Methods

This open-label, single-arm study (NCT04484857) comprised a 6-week screening period, followed by 24 weeks of treatment (with optional extension ≤1 year) and a 4-week follow-up. Patients aged ≥18 years, receiving chronic dialysis, with hemoglobin (Hb) 9.0–12.0 g/dL if converting from erythropoiesis-stimulating agents (ESAs), or <10.0 g/dL if receiving ESAs for <6 weeks, received oral roxadustat three times weekly in-center. Primary efficacy endpoints included proportion of patients with mean Hb ≥10 g/dL, averaged over weeks 16–24, and mean Hb change from baseline to the average over weeks 16–24. Safety was also assessed.

Findings

Overall, 283 patients were enrolled and treated, 282 (99.6%) were included in the full analysis set, and 216 (76.3%) continued into the extension period. Most patients enrolled were from DaVita sites (71%), with the rest from US Renal Care sites (29%). Mean (standard deviation [SD]) baseline Hb was 10.6 (0.7) g/dL. Nearly all patients were prior ESA users (n = 274; 97.2%). The proportion of patients with mean Hb ≥10 g/dL during weeks 16–24 was 83.7% (95% confidence interval 78.9–88.6). Mean (SD) Hb increase from baseline to the average over weeks 16–24 was 0.2 (1.0) g/dL. During the treatment period, 82 (29.0%) patients reported treatment-emergent serious adverse events (TESAEs). The most common TESAEs were COVID-19 pneumonia (n = 10; 3.5%), acute respiratory failure (n = 9; 3.2%), COVID-19 (n = 7; 2.5%), acute myocardial infarction (n = 7; 2.5%), and fluid overload (n = 6, 2.1%).

Discussion

Roxadustat was effective in maintaining Hb in patients with anemia of CKD on dialysis in large, community-based dialysis organizations.

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罗沙司他3b期、多中心、开放标签、单臂研究（ASPEN）：美国透析组织的操作经验。

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。ASPEN在美国透析机构评估了罗沙司他治疗CKD贫血患者的疗效、安全性和可行性。方法：这项开放标签的单臂研究（NCT04484857）包括6周的筛选期，随后24周治疗周数（可选延长≤1 一年）和4周的随访。年龄≥18岁的患者年，接受慢性透析，血红蛋白（Hb）9.0-12.0 g/dL，如果从红细胞生成刺激剂（ESA）转化而来，或结果：总的来说，283名患者被纳入并接受治疗，282名（99.6%）被纳入完整的分析集，216名（76.3%）继续进入延长期。大多数入选患者来自DaVita站点（71%），其余来自美国肾脏护理站点（29%）。平均值（标准差[SD]）基线Hb为10.6（0.7） g/dL。几乎所有患者都曾使用ESA（n = 274；97.2%）。平均Hb≥10的患者比例 16-24周的g/dL为83.7%（95%置信区间78.9-88.6）。16-24周从基线到平均值的平均（SD）Hb增加为0.2（1.0） g/dL。在治疗期间，82名（29.0%）患者报告了治疗引发的严重不良事件（TESAE）。最常见的TESAE是新冠肺炎肺炎（n = 10；3.5%）、急性呼吸衰竭（n = 9；3.2%）、新冠肺炎（n = 7.2.5%）、急性心肌梗死（n = 7.2.5%）和流体过载（n = 6，2.1%）。讨论：在大型社区透析组织中，Roxadustat在维持CKD贫血患者的Hb方面是有效的。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.