Department of Ophthalmology, Duke Reading Center, Duke University, Durham, North Carolina.
Ophthotech Corporation, New York, NY.
Ophthalmology. 2017 Feb;124(2):224-234. doi: 10.1016/j.ophtha.2016.10.010. Epub 2016 Oct 28.
To assess the safety and efficacy of E10030 (Fovista; Ophthotech, New York, NY), a platelet-derived growth factor (PDGF) antagonist, administered in combination with the anti-vascular endothelial growth factor (VEGF) agent ranibizumab (Lucentis; Roche, Basel, Switzerland) compared with ranibizumab monotherapy in patients with neovascular age-related macular degeneration (nAMD).
Phase IIb global, multicenter, randomized, prospective, double-masked, controlled superiority trial.
Four hundred forty-nine patients with treatment-naïve nAMD.
Participants were randomized in a 1:1:1 ratio to 1 of the following 3 intravitreal treatment groups: E10030 0.3 mg in combination with ranibizumab 0.5 mg, E10030 1.5 mg in combination with ranibizumab 0.5 mg, and sham in combination with ranibizumab 0.5 mg (anti-VEGF monotherapy). Drugs were administered monthly in each of the groups for a total duration of 24 weeks.
The prespecified primary end point was the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy [ETDRS] letters) from baseline to 24 weeks.
No significant safety issues were observed in any treatment group. The E10030 (1.5 mg) combination therapy regimen met the prespecified primary end point of superiority in mean VA gain compared with anti-VEGF monotherapy (10.6 compared with 6.5 ETDRS letters at week 24; P = 0.019). A dose-response relationship was evident at each measured time point commencing at 4 weeks. Visual acuity outcomes favored the E10030 1.5 mg combination therapy group regardless of baseline VA, lesion size, or central subfield thickness on optical coherence tomography. All clinically relevant treatment end points of visual benefit (≥15 ETDRS letter gain, final VA ≥20/40 or ≥20/25) and visual loss (≥1 ETDRS line loss, ≥2 ETDRS line loss, final VA ≤20/125 or ≤20/200) favored the E10030 1.5 mg combination group.
In this phase IIb clinical trial, a 62% relative benefit from baseline was noted in the E10030 1.5 mg combination therapy group compared with the anti-VEGF monotherapy group. A favorable safety and efficacy profile of E10030 combination therapy for nAMD was evident across multiple clinically relevant end points. This highly powered study provides strong rationale for a confirmatory phase III clinical trial.
评估血小板衍生生长因子（PDGF）拮抗剂 E10030（Fovista；Ophthotech，纽约，NY）与抗血管内皮生长因子（VEGF）药物 ranibizumab（Lucentis；罗氏，巴塞尔，瑞士）联合应用于治疗新生血管性年龄相关性黄斑变性（nAMD）患者的安全性和疗效。
全球、多中心、随机、前瞻性、双盲、对照优效性 2b 期临床试验。
449 名未经治疗的 nAMD 患者。
参与者按 1:1:1 的比例随机分为以下 3 组：玻璃体腔注射 E10030 0.3mg 联合 ranibizumab 0.5mg、E10030 1.5mg 联合 ranibizumab 0.5mg 和假手术联合 ranibizumab 0.5mg（抗 VEGF 单药治疗）。每组每月给药 1 次，共 24 周。
预先设定的主要终点是从基线到 24 周时视力（VA；早期治疗糖尿病视网膜病变 [ETDRS] 字母）的平均变化。
任何治疗组均未观察到明显的安全性问题。E10030（1.5mg）联合治疗方案在平均 VA 增益方面达到了优于抗 VEGF 单药治疗的预设主要终点（第 24 周时为 10.6 个 ETDRS 字母，而抗 VEGF 单药治疗为 6.5 个 ETDRS 字母；P=0.019）。从第 4 周开始，在每个测量时间点都观察到了剂量反应关系。无论基线 VA、病变大小或光学相干断层扫描的中央眼底厚度如何，视力结果均有利于 E10030 1.5mg 联合治疗组。所有与临床相关的视力获益终点（≥15 ETDRS 字母增益、最终 VA≥20/40 或≥20/25）和视力丧失终点（≥1 ETDRS 线损失、≥2 ETDRS 线损失、最终 VA≤20/125 或≤20/200）均有利于 E10030 1.5mg 联合治疗组。
在这项 2b 期临床试验中，与抗 VEGF 单药治疗组相比，E10030 1.5mg 联合治疗组从基线开始的相对获益为 62%。E10030 联合治疗 nAMD 的安全性和疗效在多个与临床相关的终点方面表现出良好的特征。这项高影响力的研究为一项确证性 3 期临床试验提供了强有力的依据。
