PURPOSE Geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), is a major cause of blindness. Even while central visual acuity remains relatively well preserved, GA often causes considerable compromise of visual function and quality of life. No treatment currently exists. We evaluated the safety and efficacy of pegcetacoplan, a complement C3 inhibitor, for treatment of GA. DESIGN Prospective, multicenter, randomized, sham-controlled phase 2 study. PARTICIPANTS Two hundred forty-six patients with GA. METHODS Patients with GA were assigned randomly in a 2:2:1:1 ratio to receive intravitreal injections of 15 mg pegcetacoplan monthly or every other month (EOM) or sham intravitreal injections monthly or EOM for 12 months with follow-up at months 15 and 18. Area and growth of GA were measured using fundus autofluorescence imaging. MAIN OUTCOME MEASURES The primary efficacy end point was mean change in square root GA lesion area from baseline to month 12. Secondary outcome measures included mean change from baseline in GA lesion area without the square root transformation, distance of GA lesion from the fovea, best-corrected visual acuity (BCVA), low-luminance BCVA, and low-luminance visual acuity deficit. The primary safety end point was the number and severity of treatment-emergent adverse events. RESULTS In patients receiving pegcetacoplan monthly or EOM, the GA growth rate was reduced by 29% (95% confidence interval [CI], 9-49; P = 0.008) and 20% (95% CI, 0-40; P = 0.067) compared with the sham treatment group. Post hoc analysis showed that the effect was greater in the second 6 months of treatment, with observed reductions of 45% (P = 0.0004) and 33% (P = 0.009) for pegcetacoplan monthly and EOM, respectively. Two cases of culture-positive endophthalmitis and 1 case of culture-negative endophthalmitis occurred in the pegcetacoplan monthly group. New-onset investigator-determined exudative AMD was reported more frequently in pegcetacoplan-treated eyes (18/86 eyes [20.9%] and 7/79 eyes [8.9%] in monthly and EOM groups, respectively) than in sham-treated eyes (1/81 eyes [1.2%]). CONCLUSIONS Local C3 inhibition with pegcetacoplan resulted in statistically significant reductions in the growth of GA compared with sham treatment. Phase 3 studies will define the efficacy and safety profile further.

中文翻译：

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补充 C3 抑制剂 Pegcetacoplan 用于继发于年龄相关性黄斑变性的地理萎缩：一项随机 2 期试验。

目的 地理萎缩 (GA) 是老年性黄斑变性 (AMD) 的晚期，是失明的主要原因。即使中心视力保持相对完好，GA 也经常导致视觉功能和生活质量的相当大的损害。目前没有治疗方法。我们评估了补体 C3 抑制剂 pegcetacoplan 治疗 GA 的安全性和有效性。设计 前瞻性、多中心、随机、假对照 2 期研究。参与者 246 名 GA 患者。方法 GA 患者以 2:2:1:1 的比例随机分配接受每月或每隔一个月 (EOM) 玻璃体内注射 15 mg pegcetacoplan 或每月或 EOM 假玻璃体内注射 12 个月，并在第 15 个月进行随访和 18。使用眼底自发荧光成像测量 GA 的面积和生长。主要结果测量 主要疗效终点是从基线到第 12 个月的平方根 GA 病变区域的平均变化。次要结果测量包括没有平方根转换的 GA 病变区域从基线的平均变化、GA 病变到中央凹的距离、最佳-矫正视力 (BCVA)、低亮度 BCVA 和低亮度视力缺陷。主要安全终点是治疗中出现的不良事件的数量和严重程度。结果 在每月接受 pegcetacoplan 或 EOM 的患者中，GA 增长率降低了 29%（95% 置信区间 [CI]，9-49；P = 0.008）和 20%（95% CI，0-40；P = 0.067） ) 与假治疗组相比。事后分析显示，在治疗的第二个 6 个月中效果更大，观察到的 pegcetacoplan 每月和 EOM 分别减少了 45% (P = 0.0004) 和 33% (P = 0.009)。pegcetacoplan每月组发生2例培养阳性眼内炎和1例培养阴性眼内炎。与假治疗眼相比，pegcetacoplan 治疗眼（每月和 EOM 组分别为 18/86 眼 [20.9%] 和 7/79 眼 [8.9%]）报告的新发研究人员确定的渗出性 AMD 更频繁（ 1/81 只眼睛 [1.2%]）。结论 与假治疗相比，pegcetacoplan 的局部 C3 抑制导致 GA 生长的统计学显着降低。第三阶段的研究将进一步确定疗效和安全性。0004) 和 33% (P = 0.009) 分别为 pegcetacoplan 每月和 EOM。pegcetacoplan每月组发生2例培养阳性眼内炎和1例培养阴性眼内炎。与假治疗眼相比，pegcetacoplan 治疗眼（每月和 EOM 组分别为 18/86 眼 [20.9%] 和 7/79 眼 [8.9%]）报告新发的研究者确定的渗出性 AMD 的频率更高（ 1/81 只眼睛 [1.2%]）。结论 与假治疗相比，pegcetacoplan 的局部 C3 抑制导致 GA 生长的统计学显着降低。第三阶段的研究将进一步确定疗效和安全性。0004) 和 33% (P = 0.009) 分别为 pegcetacoplan 每月和 EOM。pegcetacoplan每月组发生2例培养阳性眼内炎和1例培养阴性眼内炎。与假治疗眼相比，pegcetacoplan 治疗眼（每月和 EOM 组分别为 18/86 眼 [20.9%] 和 7/79 眼 [8.9%]）报告新发的研究者确定的渗出性 AMD 的频率更高（ 1/81 只眼睛 [1.2%]）。结论 与假治疗相比，pegcetacoplan 的局部 C3 抑制导致 GA 生长的统计学显着降低。第三阶段的研究将进一步确定疗效和安全性。与假治疗眼相比，pegcetacoplan 治疗眼（每月和 EOM 组分别为 18/86 眼 [20.9%] 和 7/79 眼 [8.9%]）报告的新发研究人员确定的渗出性 AMD 更频繁（ 1/81 只眼睛 [1.2%]）。结论 与假治疗相比，pegcetacoplan 的局部 C3 抑制导致 GA 生长的统计学显着降低。第三阶段的研究将进一步确定疗效和安全性。与假治疗眼相比，pegcetacoplan 治疗眼（每月和 EOM 组分别为 18/86 眼 [20.9%] 和 7/79 眼 [8.9%]）报告的新发研究人员确定的渗出性 AMD 更频繁（ 1/81 只眼睛 [1.2%]）。结论 与假治疗相比，pegcetacoplan 的局部 C3 抑制导致 GA 生长的统计学显着降低。第三阶段的研究将进一步确定疗效和安全性。