Telitacicept for IgA Nephropathy - Interim Analysis of a Phase 3 Trial.

Telitacicept is a fusion protein that targets and neutralizes both BAFF and APRIL and, as such, might be effective in IgA nephropathy.

Telitacicept是一种融合蛋白，它针对并中和了BAFF和APRIL，因此可能对IgA肾病有效。

Methods

We now report a prespecified interim analysis of a phase 3, multicenter, double-blind, randomized, placebo-controlledtrial, which enrolled adults with biopsy-proven IgA nephropathy and persistent proteinuria (protein level, ≥1.0 g per day), despite appropriate supportive care.

我们现在报告了一项预先设定的第3阶段、多中心、双盲、随机、安慰剂对照试验的中期分析结果，该试验招募了经活检证实的IgA肾病成人患者，并且尽管接受了适当的对症治疗，仍存在持续性蛋白尿（蛋白水平≥1.0克/天）。

Patients were randomly assigned in a 1:1 ratio to receive subcutaneous once-weekly telitacicept (240 mg) or matching placebo.

患者按1:1的比例随机分配，每周一次皮下注射telitacicept（240毫克）或匹配的安慰剂。

The primary end point was the geometric mean ratio of the 24-hour urinary protein-to-creatinine ratio at 39 weeks relative to baseline.

主要终点是39周相对于基线的24小时尿蛋白与肌酐比值的几何平均比。

Safety was also evaluated.

同时评估了安全性。

Results

A total of 318 patients were assigned to receive telitacicept or placebo (159 in each group).

共有318名患者被分配接受telitacicept或安慰剂治疗（每组159人）。

At week 39, the percentage change in the 24-hour urinary protein-to-creatinine ratio was -58.9% with telitacicept and -8.8% with placebo, which corresponded to a relative difference (based on the ratio of geometric mean reductions between the two groups) of -55.0% (95% confidence interval[CI], -61.3 to -47.6; P<0.001) in favor of active medication.

在第39周时，24小时尿蛋白/肌酐比值的百分比变化为：telitacicept组为-58.9%，安慰剂组为-8.8%，相对差异（基于两组几何平均减少率的比率）为-55.0%（95%置信区间[CI]，-61.3至-47.6；P<0.001），有利于活性药物。

The percentage change in the estimated glomerular filtration rate relative to baseline was -1.0% (95% CI, -3.2 to 1.2) with telitacicept and -7.7% (95% CI, -9.9 to -5.4) with placebo.

与基线相比，telitacicept组的估算肾小球滤过率百分比变化为-1.0%（95% 置信区间，-3.2至1.2），而安慰剂组为-7.7%（95% 置信区间，-9.9至-5.4）。

Adverse events were more common with telitacicept than with placebo (in 89.3% vs. 78.6% of patients), although serious adverse events were less common (in 2.5% vs. 8.2%).

与安慰剂相比，telitacicept组的不良事件更为常见（在89.3%的患者中出现，而安慰剂组为78.6%），尽管严重不良事件较少（在2.5%的患者中出现，而安慰剂组为8.2%）。

No unexpected safety findings were reported with telitacicept.

使用telitacicept未报告意外的安全性发现。

Conclusions

In patients with IgA nephropathy at high risk for progression, 39 weeks of treatment with telitacicept led to a greater reduction in the 24-hour urinary protein-to-creatinine ratio than placebo.

在高风险进展的IgA肾病患者中，与安慰剂相比，telitacicept治疗39周后，24小时尿蛋白与肌酐比值的降低更为显著。

(Funded by RemeGen; TELIGAN ClinicalTrials.gov number, NCT05799287.).

(由RemeGen资助; TELIGAN ClinicalTrials.gov编号, NCT05799287.)