Efficacy and safety of a targeted-release formulation of budesonide in patients with primary IgA nephropathy (NefIgArd): 2-year results from a randomised phase 3 trial

医学 蛋白尿 临床终点 内科学 肾病 肾功能 安慰剂 肾脏疾病 临床试验 胃肠病学 病理 内分泌学 糖尿病 替代医学
作者
Richard A. Lafayette,Jens Kristensen,Andrew Stone,Jürgen Floege,Vladimı́r Tesař,Hernán Trimarchi,Hong Zhang,Necmi Eren,Alexander Paliege,Heather N. Reich,Brad H. Rovin,Jonathan Barratt
出处
期刊:The Lancet [Elsevier]
卷期号:402 (10405): 859-870 被引量:73
标识
DOI:10.1016/s0140-6736(23)01554-4
摘要

IgA nephropathy is a chronic immune-mediated kidney disease and a major cause of kidney failure worldwide. The gut mucosal immune system is implicated in its pathogenesis, and Nefecon is a novel, oral, targeted-release formulation of budesonide designed to act at the gut mucosal level. We present findings from the 2-year, phase 3 NefIgArd trial of Nefecon in patients with IgA nephropathy.In this phase 3, multicentre, randomised, double-blind, placebo-controlled trial, adult patients (aged ≥18 years) with primary IgA nephropathy, estimated glomerular filtration rate (eGFR) 35-90 mL/min per 1·73 m2, and persistent proteinuria (urine protein-creatinine ratio ≥0·8 g/g or proteinuria ≥1 g/24 h) despite optimised renin-angiotensin system blockade were enrolled at 132 hospital-based clinical sites in 20 countries worldwide. Patients were randomly assigned (1:1) to receive 16 mg/day oral capsules of Nefecon or matching placebo for 9 months, followed by a 15-month observational follow-up period off study drug. Randomisation via an interactive response technology system was stratified according to baseline proteinuria (<2 or ≥2 g/24 h), baseline eGFR (<60 or ≥60 mL/min per 1·73 m2), and region (Asia-Pacific, Europe, North America, or South America). Patients, investigators, and site staff were masked to treatment assignment throughout the 2-year trial. Optimised supportive care was also continued throughout the trial. The primary efficacy endpoint was time-weighted average of eGFR over 2 years. Efficacy and safety analyses were done in the full analysis set (ie, all randomly assigned patients). The trial was registered on ClinicalTrials.gov, NCT03643965, and is completed.Patients were recruited to the NefIgArd trial between Sept 5, 2018, and Jan 20, 2021, with 364 patients (182 per treatment group) randomly assigned in the full analysis set. 240 (66%) patients were men and 124 (34%) were women, and 275 (76%) identified as White. The time-weighted average of eGFR over 2 years showed a statistically significant treatment benefit with Nefecon versus placebo (difference 5·05 mL/min per 1·73 m2 [95% CI 3·24 to 7·38], p<0·0001), with a time-weighted average change of -2·47 mL/min per 1·73 m2 (95% CI -3·88 to -1·02) reported with Nefecon and -7·52 mL/min per 1·73 m2 (-8·83 to -6·18) reported with placebo. The most commonly reported treatment-emergent adverse events during treatment with Nefecon were peripheral oedema (31 [17%] patients, vs placebo, seven [4%] patients), hypertension (22 [12%] vs six [3%]), muscle spasms (22 [12%] vs seven [4%]), acne (20 [11%] vs two [1%]), and headache (19 [10%] vs 14 [8%]). No treatment-related deaths were reported.A 9-month treatment period with Nefecon provided a clinically relevant reduction in eGFR decline and a durable reduction in proteinuria versus placebo, providing support for a disease-modifying effect in patients with IgA nephropathy. Nefecon was also well tolerated, with a safety profile as expected for a locally acting oral budesonide product.Calliditas Therapeutics.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
亦已歌发布了新的文献求助10
刚刚
Jasper应助yrh采纳,获得10
刚刚
lu0530关注了科研通微信公众号
1秒前
2秒前
2秒前
俊逸凌雪完成签到,获得积分10
2秒前
serendipity发布了新的文献求助10
4秒前
lklk完成签到 ,获得积分10
4秒前
1111完成签到,获得积分10
4秒前
陳.发布了新的文献求助10
5秒前
5秒前
俊逸凌雪发布了新的文献求助30
6秒前
小二郎应助LSY采纳,获得10
6秒前
Doc邓爱科研完成签到,获得积分10
7秒前
7秒前
茶壶完成签到,获得积分10
8秒前
无足鸟发布了新的文献求助10
8秒前
rrr发布了新的文献求助20
8秒前
10秒前
研友_VZG7GZ应助夏轩采纳,获得10
11秒前
11秒前
12秒前
12秒前
13秒前
13秒前
嘻嘻发布了新的文献求助10
13秒前
14秒前
阿萨斯完成签到,获得积分10
14秒前
chali48发布了新的文献求助10
16秒前
NexusExplorer应助Lloyd_Lee采纳,获得10
16秒前
16秒前
17秒前
二大爷完成签到,获得积分10
18秒前
yrh发布了新的文献求助10
18秒前
大模型应助hs采纳,获得10
20秒前
Hello应助_xySH采纳,获得10
20秒前
昭华昭华发布了新的文献求助10
20秒前
21秒前
大洋洋发布了新的文献求助10
21秒前
lu0530发布了新的文献求助10
22秒前
高分求助中
좌파는 어떻게 좌파가 됐나:한국 급진노동운동의 형성과 궤적 2500
Sustainability in Tides Chemistry 1500
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
CLSI EP47 Evaluation of Reagent Carryover Effects on Test Results, 1st Edition 800
Threaded Harmony: A Sustainable Approach to Fashion 799
Livre et militantisme : La Cité éditeur 1958-1967 500
Retention of title in secured transactions law from a creditor's perspective: A comparative analysis of selected (non-)functional approaches 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3054832
求助须知:如何正确求助?哪些是违规求助? 2711702
关于积分的说明 7427649
捐赠科研通 2356261
什么是DOI,文献DOI怎么找? 1247983
科研通“疑难数据库(出版商)”最低求助积分说明 606566
版权声明 596083