A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy.

In at least 50% of patients, IgA nephropathy leads to kidney failure or death within 10 to 20 years after diagnosis.

在至少50%的患者中，IgA肾病会导致在诊断后10至20年内出现肾功能衰竭或死亡。

Atacicept is a native human transmembrane activator and calcium-modulator and cyclophilin-ligand interactor (TACI)-Fc fusion protein that inhibits two key immunoregulatory cytokines - B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) - that are thought to be central to the pathophysiology of IgA nephropathy.

Atacicept 是一种天然的人类跨膜激活剂和钙调节剂以及环孢素配体相互作用蛋白（TACI）-Fc 融合蛋白，它抑制了两种关键的免疫调节细胞因子——B细胞激活因子（BAFF）和增殖诱导配体（APRIL），这两种因子被认为在 IgA 肾病的病理生理学中起着核心作用。

Methods

In this ongoing, phase 3, multicenter, double-blind, randomized, placebo-controlledtrial, we assigned patients with IgA nephropathy in a 1:1 ratio to receive atacicept at a dose of 150 mg once weekly, administered subcutaneously by patients at home, or matching placebo.

在这项正在进行的 III 期、多中心、双盲、随机、安慰剂对照试验中，我们将 IgA 肾病患者以 1:1 的比例分配，接受每周一次 150 mg 的 atacicept，由患者在家中皮下注射，或匹配的安慰剂。

The primary end point was the percentage change from baseline in the 24-hour urinary protein-to-creatinine ratio at week 36.

主要终点是第36周时24小时尿蛋白与肌酐比值从基线变化的百分比。

Safety was also evaluated.

同时评估了安全性。

Results

A total of 203 patients were included in the prespecified interim analysis: 106 patients in the atacicept group and 97 in the placebo group.

共有203名患者被纳入预先设定的中期分析：其中106名患者在atacicept组，97名患者在安慰剂组。

At week 36, the percentage reduction from baseline in the urinary protein-to-creatinine ratio was 45.7% in the atacicept group and 6.8% in the placebo group, with a geometric mean between-group difference of 41.8 percentage points (95% confidence interval, 28.9 to 52.3; P<0.001).

在第36周时，从基线开始的尿蛋白与肌酐比值的百分比降低在atacicept组为45.7%，在安慰剂组为6.8%，两组间几何平均差异为41.8个百分点（95%置信区间，28.9至52.3；P<0.001）。

Adverse events were observed in 59.3% of the patients in the atacicept group and in 50.0% in the placebo group; most were mild or moderate in severity.

在阿塔西普组中，59.3%的患者观察到不良事件，在安慰剂组中为50.0%；大多数不良事件的严重程度为轻度或中度。

Conclusions

In this prespecified interim analysis, treatment with atacicept resulted in a significantly greater reduction in proteinuria than placebo at week 36 in patients with IgA nephropathy.

在这项预先设定的中期分析中，与安慰剂相比，阿塔西普治疗在第36周时在IgA肾病患者中导致蛋白尿显著减少。

(Funded by Vera Therapeutics; ORIGIN 3 ClinicalTrials.gov number, NCT04716231.).

(由Vera Therapeutics资助; ORIGIN 3临床试验注册号, NCT04716231.)