美国马萨诸塞州Visterra公司Mohit Mathur团队分析了Sibeprenlimab治疗IgA肾病的2期临床研究。这一研究成果发表在2023年11月2日出版的《新英格兰医学杂志》上。

A增殖诱导配体（APRIL）与IgA肾病的发病机制有关。Sibeprenlimab是一种人源化IgG2单克隆抗体，可结合并中和APRIL。

在这项临床2期、多中心、双盲、随机、安慰剂对照的平行组试验中，研究组招募患有活检证实IgA肾病的成年人，尽管接受了标准护理治疗，但仍有疾病进展的高风险，以1:1:1:1的比例将其随机分配，分别接受每公斤体重2、4或8mg的Sibeprenlimab，或安慰剂治疗，每月一次，持续12个月。主要终点是第12个月时24小时尿蛋白与肌酸酐比值的对数转换与基线相比的变化。次要终点包括第12个月估计肾小球滤过率（eGFR）与基线相比的变化。还对安全性进行了评估。

在155名接受随机分组的患者中，38名、41名、38名患者分别接受了剂量为每公斤体重2mg、4mg和8mg的Sibeprenlimab，38名患者服用安慰剂。在12个月时，Sibeprenlimab每公斤体重2mg、4mg和8mg组和安慰剂组患者的24小时尿蛋白与肌酸酐比率的几何平均比降低（±SE）分别为47.2±8.2%、58.8±6.1%、62.0±5.7%和20.0±12.6%。

在12个月时，Sibeprenlimab每公斤体重2mg、4mg和8mg组和安慰剂组的eGFR与基线相比的最小二乘平均值（±SE）变化分别为−2.7±1.8、0.2±1.7、−1.5±1.8和−7.4±1.8 ml/min/1.73 m²。Sibeprenlimab或安慰剂开始给药后发生不良事件的发生率，Sibeprenlimab合并组为78.6%，安慰剂组为71.1%。

研究结果表明，在IgA肾病患者中，与安慰剂相比，Sibeprenlimab治疗12个月可显著降低蛋白尿。

附：英文原文

Title: A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy | NEJM

Author: anonymous

Issue&Volume: 2023-1102

Abstract:

Background

A proliferation-inducing ligand (APRIL) is implicated in the pathogenesis of IgA nephropathy. Sibeprenlimab is a humanized IgG2 monoclonal antibody that binds to and neutralizes APRIL.

Methods

In this phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial, we randomly assigned adults with biopsy-confirmed IgA nephropathy who were at high risk for disease progression, despite having received standard-care treatment, in a 1:1:1:1 ratio to receive intravenous sibeprenlimab at a dose of 2, 4, or 8 mg per kilogram of body weight or placebo once monthly for 12 months. The primary end point was the change from baseline in the log-transformed 24-hour urinary protein-to-creatinine ratio at month 12. Secondary end points included the change from baseline in the estimated glomerular filtration rate (eGFR) at month 12. Safety was also assessed.

Results

Among 155 patients who underwent randomization, 38 received sibeprenlimab at a dose of 2 mg per kilogram, 41 received sibeprenlimab at a dose of 4 mg per kilogram, 38 received sibeprenlimab at a dose of 8 mg per kilogram, and 38 received placebo. At 12 months, the geometric mean ratio reduction (±SE) from baseline in the 24-hour urinary protein-to-creatinine ratio was 47.2±8.2%, 58.8±6.1%, 62.0±5.7%, and 20.0±12.6% in the sibeprenlimab 2-mg, 4-mg, and 8-mg groups and the placebo group, respectively. At 12 months, the least-squares mean (±SE) change from baseline in eGFR was 2.7±1.8, 0.2±1.7, 1.5±1.8, and 7.4±1.8 ml per minute per 1.73 m2 in the sibeprenlimab 2-mg, 4-mg, and 8-mg groups and the placebo group, respectively. The incidence of adverse events that occurred after the start of administration of sibeprenlimab or placebo was 78.6% in the pooled sibeprenlimab groups and 71.1% in the placebo group.

Conclusions

In patients with IgA nephropathy, 12 months of treatment with sibeprenlimab resulted in a significantly greater decrease in proteinuria than placebo.

DOI: 10.1056/NEJMoa2305635

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2305635