近日，美国斯坦福大学Richard Lafayette团队研究了阿塞西普治疗IgA肾病的3期临床试验。相关论文于2025年11月6日发表在《新英格兰医学杂志》上。

IgA肾病是世界范围内最常见的原发性肾小球疾病，是一种以含IgA免疫复合物肾小球系膜积聚为特征的B细胞源性肾脏疾病。在至少50%的患者中，IgA肾病在诊断后10至20年内导致肾衰竭或死亡。阿塞西普是一种天然的人跨膜激活剂和钙调节剂和亲环素配体相互作用(TACI)–Fc融合蛋白，可抑制两种关键的免疫调节细胞因子-B细胞活化因子（BAFF）和增殖诱导配体(APRIL) ，二者被认为是IgA肾病病理生理学的核心。

在这项正在进行的3期、多中心、双盲、随机、安慰剂对照试验中，研究组将IgA肾病患者按1:1的比例分配给阿塞西普，剂量为150mg，每周一次，由患者在家皮下给药，或匹配安慰剂。主要终点是第36周24小时尿蛋白与肌酐比值的基线变化百分比。安全性也进行了评估。

在预先设定的中期分析中，共有203例患者被纳入：阿塞西普组106例，安慰剂组97例。在第36周，阿塞西普组尿蛋白与肌酐比值较基线下降的百分比为45.7%，安慰剂组为6.8%，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）。阿塞西普组不良事件发生率为59.3%，安慰剂组为50.0%；大多数是轻度或中度的严重程度。

研究结果表明，在这项预先指定的中期分析中，在IgA肾病患者第36周，阿塞西普治疗导致蛋白尿的减少明显大于安慰剂。

附：英文原文

Title: A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy

Author: Richard Lafayette, Sean J. Barbour, Robert M. Brenner, Kirk N. Campbell, Tom Doan, Necmi Eren, Jürgen Floege, Vivekanand Jha, Beom Seok Kim, Adrian Liew, Bart Maes, Atanu Pal, Roberto Pecoits-Filho, Richard K.S. Phoon, Dana V. Rizk, Hitoshi Suzuki, Vladimir Tesa, Hernán Trimarchi, Xuelian Wei, Hong Zhang, Jonathan Barratt

Issue&Volume: 2025-11-06

Abstract:

BACKGROUND

IgA nephropathy, the most common primary glomerulopathy worldwide, is a kidney disorder of B-cell origin characterized by mesangial accumulation of IgA-containing immune complexes. In at least 50% of patients, IgA nephropathy leads to kidney failure or death within 10 to 20 years after diagnosis. 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.

METHODS

In this ongoing, phase 3, multicenter, double-blind, randomized, placebo-controlled trial, 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. The primary end point was the percentage change from baseline in the 24-hour urinary protein-to-creatinine ratio at week 36. Safety was also evaluated.

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. 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). 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.

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.

DOI: NJ202511060000002

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2510198