Iptacopan in IgA Nephropathy - Final 24-Month Data.

In the 9-month interim analysis of this phase 3 trial, iptacopan, a complement factor B inhibitor, led to a significant reduction of 38.3% in the 24-hour urinary protein-to-creatinine ratio as compared with placebo and had an acceptable safety profile.

在这项3期试验的9个月中期分析中，补体因子B抑制剂iptacopan与安慰剂相比，导致24小时尿蛋白与肌酐比值显著降低了38.3%，且具有可接受的安全性。

Methods

In this phase 3 trial, we enrolled adults who had IgA nephropathy, an estimated glomerular filtration rate (eGFR) of at least 30 ml per minute per 1.73 m2 of body-surface area, and a 24-hour urinary protein-to-creatinine ratio of 1 or higher (with protein and creatinine both measured in grams) despite supportive care.

在这项III期试验中，我们招募了患有IgA肾病的成年人，他们的估算肾小球滤过率（eGFR）至少为每分钟每1.73平方米体表面积30毫升，以及24小时尿蛋白与肌酐比值为1或更高（蛋白和肌酐均以克为单位），尽管接受了支持性治疗。

Patients were randomly assigned, in a 1:1 ratio, to receive oral iptacopan (200 mg) or placebo twice daily.

患者按1:1的比例随机分配，每天两次口服iptacopan（200毫克）或安慰剂。

The primary end point for the final analysis was the annualized total eGFR slope as estimated over a 24-month period.

最终分析的主要终点是24个月内估算的年化总eGFR斜率。

Secondary end points included a composite kidney-failure end point (i.e., a sustained decline in eGFR of ≥30%, a sustained eGFR of <15 ml per minute per 1.73 m2, the initiation of maintenance dialysis, receipt of kidney transplant, or death from kidney failure), assessed in a time-to-event analysis.

次要终点包括一个综合肾衰竭终点（即eGFR持续下降≥30%，持续eGFR<15 ml/分钟/1.73 m²，开始维持性透析，接受肾脏移植或因肾衰竭死亡），通过时间至事件分析进行评估。

Safety was also assessed.

安全性也得到了评估。

Results

Among 477 patients included in the final analysis, 238 had been randomly assigned to iptacopan and 239 to placebo.

在最终分析中包括的477名患者中，有238名被随机分配到iptacopan组，239名被分配到安慰剂组。

The annualized total eGFR slope was -3.10 ml per minute per 1.73 m2 per year with iptacopan, as compared with -6.12 ml per minute per 1.73 m2 per year with placebo (difference, 3.02 ml per minute per 1.73 m2 per year; 95% confidence interval[CI], 2.02 to 4.01; adjusted P<0.001).

使用iptacopan的患者年化总eGFR斜率为每1.73平方米每分钟-3.10毫升，与使用安慰剂的患者相比，后者为每1.73平方米每分钟-6.12毫升（差异，每1.73平方米每分钟3.02毫升；95%置信区间[CI]，2.02至4.01；调整后P<0.001）。

A composite kidney-failure end-point event occurred in 21.4% of the patients in the iptacopan group, as compared with 33.5% of those in the placebo group (hazard ratio, 0.57; 95% CI, 0.40 to 0.81; adjusted P = 0.003).

iptacopan组中有21.4%的患者发生了复合肾功能衰竭终点事件，而安慰剂组中这一比例为33.5%（风险比，0.57；95%置信区间[CI]，0.40至0.81；调整后P = 0.003）。

The incidenceof adverse events was 87.0% in the iptacopan group and 89.1% in the placebo group.

iptacopan组不良事件的发生率为87.0%，安慰剂组为89.1%。

Serious adverse events occurred in 12.2% of the patients who received iptacopan and in 11.7% of those who received placebo, and serious infections in 6.7% and 2.1%, respectively.

接受iptacopan治疗的患者中有12.2%发生了严重不良事件，而接受安慰剂治疗的患者中有11.7%发生了严重不良事件，严重感染的发生率分别为6.7%和2.1%。

No deaths occurred.

未发生任何死亡事件。

Conclusions

Iptacopan therapy led to a significantly slower decline in kidney function than placebo.

Iptacopan治疗相较于安慰剂显著延缓了肾功能的下降。

(Funded by Novartis; APPLAUSE-IgAN ClinicalTrials.gov number, NCT04578834.).

(由诺华制药资助; APPLAUSE-IgAN临床试验注册号, NCT04578834.)