Sibeprenlimab in IgA Nephropathy - Interim Analysis of a Phase 3 Trial.

Sibeprenlimab, a humanized IgG2 monoclonal antibody, selectively binds to and inhibits APRIL.

Sibeprenlimab是一种人源化IgG2单克隆抗体，它选择性地结合并抑制APRIL。

Methods

In this phase 3, multicenter, double-blind, randomized, placebo-controlledtrial, we assigned adults with biopsy-confirmed IgA nephropathy in a 1:1 ratio to receive either subcutaneous sibeprenlimab at a dose of 400 mg or placebo administered every 4 weeks for 100 weeks.

在这项III期、多中心、双盲、随机、安慰剂对照试验中，我们按1:1的比例将经活检证实的IgA肾病成人患者分配接受皮下注射400 mg的sibeprenlimab或安慰剂，每4周一次，持续100周。

The primary end point for this interim analysis was the 24-hour urinary protein-to-creatinine ratio at 9 months as compared with baseline.

本次中期分析的主要终点是与基线相比，9个月时的24小时尿蛋白与肌酐比值。

The key secondary end point, to be reported at trial completion, is the annualized slope of estimated glomerular filtration rate over 24 months.

将在试验结束时报告的关键次要终点是24个月内估算肾小球滤过率的年化斜率。

Other secondary end points included the change in the level of serum immunoglobulin and safety.

其他次要终点包括血清免疫球蛋白水平的变化和安全性。

Exploratory end points included the change in galactose-deficient IgA1 and APRIL concentrations, the spot 24-hour urinary protein-to-creatinine ratio, hematuria, and remission of proteinuria.

探索性终点包括半乳糖缺陷型IgA1和APRIL浓度的变化、24小时尿蛋白与肌酐比值、血尿以及蛋白尿的缓解。

Results

A total of 510 patients underwent randomization - 259 to the sibeprenlimab group and 251 to the placebo group.

共有510名患者进行了随机分组 - 259名患者分入西贝普利单抗组，251名患者分入安慰剂组。

The prespecified interim analysis included the first 320 patients (152 who received sibeprenlimab and 168 who received placebo) who had the opportunity to complete the 9-month evaluation of the 24-hour urinary protein-to-creatinine ratio.

预先设定的中期分析包括了前320名有机会完成24小时尿蛋白/肌酐比值9个月评估的患者（152名接受sibeprenlimab治疗和168名接受安慰剂治疗）。

At 9 months, a significant reduction in 24-hour urinary protein-to-creatinine ratio was observed with sibeprenlimab (-50.2%) as compared with an increase with placebo (2.1%), corresponding to an adjusted geometric least-squares mean 24-hour urinary protein-to-creatinine ratio that was 51.2% (96.5% confidence interval[CI], 42.9 to 58.2) lower with sibeprenlimab than with placebo (P<0.001).

在9个月时，与安慰剂组（增加2.1%）相比，接受sibeprenlimab治疗的患者观察到24小时尿蛋白/肌酐比值显著降低（-50.2%），调整后的几何最小二乘均值24小时尿蛋白/肌酐比值在sibeprenlimab组比安慰剂组低51.2%（96.5%置信区间[CI]，42.9至58.2），差异具有统计学意义（P<0.001）。

The levels of APRIL and pathogenic galactose-deficient IgA1 at week 48 were reduced from baseline by 95.8% and 67.1%, respectively, with sibeprenlimab.

在第48周时，APRIL和病原性半乳糖缺乏IgA1的水平分别从基线下降了95.8%和67.1%，这是在使用sibeprenlimab的情况下观察到的。

The safety profile appeared to be similar with sibeprenlimab and placebo.

sibeprenlimab的安全性特征似乎与安慰剂相似。

No deaths were reported, and the incidenceof serious adverse events that occurred during the treatment period was 3.5% with sibeprenlimab and 4.4% with placebo.

在治疗期间，未报告死亡事件，且严重不良事件的发生率在接受西贝普雷利单抗治疗的患者中为3.5%，在接受安慰剂治疗的患者中为4.4%。

Conclusions

Sibeprenlimab resulted in a significant reduction in proteinuria as compared with placebo in patients with IgA nephropathy.

与安慰剂相比，西贝普雷利单抗在IgA肾病患者中显著减少了蛋白尿。

(Funded by Otsuka Pharmaceutical Development and Commercialization.

(由大冢制药开发和商业化资助。)

VISIONARY ClinicalTrials.gov number, NCT05248646.).

VISIONARY 临床试验注册号，ClinicalTrials.gov NCT05248646。