Trial of Pegcetacoplan in C3 Glomerulopathy and Immune-Complex MPGN.

The efficacy and safety of pegcetacoplan, a C3 and C3b inhibitor, in persons with C3 glomerulopathy or primary immune-complex MPGN are unclear.

Pegcetacoplan（一种C3和C3b抑制剂）在C3肾小球病或原发性免疫复合物MPGN患者中的疗效和安全性尚不明确。

Methods

We conducted a phase 3, double-blind, placebo-controlledtrial involving adolescents and adults with C3 glomerulopathy or primary immune-complex MPGN, including those with native kidney disease and those with disease recurrence after transplantation.

我们开展了一项III期、双盲、安慰剂对照试验，对象为患有C3肾小球病变或原发性免疫复合物型膜性增生性肾小球肾炎（MPGN）的青少年和成人，包括原发肾脏疾病患者以及移植后疾病复发患者。

Patients were randomly assigned in a 1:1 ratio to receive pegcetacoplan or placebo.

患者按1:1的比例随机分配接受Pegcetacoplan或安慰剂治疗。

The primary end point was the log-transformed ratio of the urinary protein-to-creatinine ratio at week 26 as compared with baseline.

主要终点是第26周相对于基线时尿蛋白与肌酐比值的对数变换比率。

Results

A total of 124 patients underwent randomization.

共有124名患者进行了随机分组。

The change in proteinuria (as measured by the log-transformed ratio to baseline in the urinary protein-to-creatinine ratio) was significantly greater with pegcetacoplan than with placebo (geometric mean of the urinary protein-to-creatinine ratio, -67.2% [95% confidence interval{CI}, -74.9 to -57.2] vs. 2.9% [95% CI, -8.6 to 15.9]).

与安慰剂相比，pegcetacoplan在蛋白尿变化（通过尿蛋白与肌酐比值的对数转换比值测量）方面显著更大（尿蛋白与肌酐比值的几何平均数，-67.2% [95% 置信区间 {CI}, -74.9至-57.2] 对比 2.9% [95% CI, -8.6至15.9]）。

The difference represents a relative reduction of 68.1% (95% CI, 57.3 to 76.2) as compared with placebo.

与安慰剂相比，差异代表了相对减少68.1%（95% 置信区间，57.3至76.2）。

In hierarchical testing of five secondary end points, significantly higher percentages of patients in the pegcetacoplan group than in the placebo group met the composite renal end-point criteria (stabilization of estimated glomerular filtration rate [eGFR] and ≥50% reduction in urinary protein-to-creatinine ratio) (49% vs. 3%) and had at least a 50% reduction in the protein-to-creatinine ratio (60% vs. 5%).

在对五个次要终点进行分层测试时，与安慰剂组相比，接受佩格塞他普朗治疗的患者中显著更高比例的患者达到了复合肾脏终点标准（估算肾小球滤过率[eGFR]稳定和尿蛋白肌酐比值≥50%的降低）（49%对3%），并且至少有50%的蛋白肌酐比值降低（60%对5%）。

Among 69 patients with evaluable kidney-biopsy samples, the change in the activity score of the C3 glomerulopathy histologic index did not differ significantly between the two groups; subsequent end points (decrease in C3 staining and change in eGFR) were not formally tested.

在69名有可评估肾活检样本的患者中，C3肾小球病变组织学指数的活动评分在两组之间的变化没有显著差异；随后的终点（C3染色减少和eGFR变化）没有进行正式测试。

Pegcetacoplan was not associated with more adverse events than placebo.

Pegcetacoplan与安慰剂相比，并未关联更多的不良事件。

No serious infections from encapsulated bacteria occurred; 1 patient receiving pegcetacoplan died from coronavirus disease 2019 pneumonia.

未发生由包被细菌引起的严重感染；1名接受Pegcetacoplan治疗的患者死于2019冠状病毒病肺炎。

No allograft rejection or loss occurred.

未发生任何移植物排斥反应或丢失。

Conclusions

Pegcetacoplan resulted in a significantly greater reduction in proteinuria than placebo among patients with C3 glomerulopathy or primary immune-complex MPGN.

在患有C3肾小球病或原发性免疫复合物MPGN的患者中，Pegcetacoplan相较于安慰剂显著降低了蛋白尿。

(Funded by Apellis Pharmaceuticals and Sobi [Swedish Orphan Biovitrum]; VALIANT ClinicalTrials.gov number, NCT05067127.).

(由Apellis制药公司和Sobi [瑞典孤儿生物维特鲁姆]资助；VALIANT临床试验注册号，NCT05067127。)