目的:新生血管(湿性)年龄相关性黄斑变性(nAMD)由血管内皮生长因子(VEGF)-A驱动,-C和-D,促进血管生成和血管通透性。玻璃体内注射抗VEGF-A药物是治疗的标准,但这些不抑制VEGF-C和-D,这可以解释为什么许多患者不能完全反应。该试验旨在测试OPT-302的安全性和有效性,OPT-302是一种VEGF-C和-D的生物抑制剂,与抗VEGF-A抑制剂雷珠单抗联合使用。
方法:剂量范围,2b阶段,随机化,双面蒙面,假对照试验。
方法:接受初治nAMD治疗的参与者来自欧洲109个研究中心,以色列,和美国。
方法:参与者被随机分为六个,每周4次,玻璃体内注射0.5mgOPT-302,2.0mgOPT-302或假手术;加上玻璃体内0.5mg雷珠单抗。
方法:主要结果是24周时早期治疗糖尿病视网膜病变研究(ETDRS)最佳矫正视力(BCVA)的平均变化。次要结果(基线与第24周比较)是获得或丢失≥15个ETDRSBCVA字母的参与者比例;ETDRSBCVA随时间变化的曲线下面积;谱域光学相干断层扫描(SD-OCT)中央子场厚度(CST)的变化;以及SD-OCT上视网膜内液和视网膜下液的变化。
结果:在2017年12月1日至2018年11月30日招募的366名参与者中,122、123和121名分别被随机分配至0.5mgOPT-302,2.0mgOPT-302或假手术。2.0mgOPT-302组的平均(±标准偏差)视力增长显着优于假手术(14.2±11.61对10.8±11.52字母;p=0.01)。0.5mgOPT-302组与假手术组没有显着差异(9.44±11.32个字母;p=0.83)。与假相比,次要BCVA结果有利于2.0mgOPT-302组,结构结果有利于两个OPT-302剂量组。各组的不良事件相似,16(13.3%),7(5.6%)和10(8.3%)较低剂量的参与者,高剂量和假手术组出现至少一个严重不良事件。两个无关的死亡都发生在假手臂中。
结论:OPT-3022.0mg联合治疗可观察到明显优越的视力增强,相对于护理标准,具有良好的安全性(ClinicalTrials.gov标识符:NCT03345082)。
Neovascular (wet) age-related macular degeneration (nAMD) is driven by VEGFs A, C, and D, which promote angiogenesis and vascular permeability. Intravitreal injections of anti-VEGF-A drugs are the standard of care, but these do not inhibit VEGF-C and D, which may explain why many patients fail to respond fully. This
trial aimed to test the safety and efficacy of OPT-302, a biologic inhibitor of VEGF-C and D, in combination with the anti-VEGF-A inhibitor ranibizumab.
Dose-ranging, phase 2b, randomized, double-masked, sham-controlled
trial.
Participants with treatment-naive nAMD were enrolled from 109 sites across Europe, Israel, and the United States.
Participants were randomized to 6, 4-weekly, intravitreal injections of 0.5 mg OPT-302, 2.0 mg OPT-302, or sham, plus intravitreal 0.5 mg ranibizumab.
The primary outcome was mean change in ETDRS best-corrected visual acuity (BCVA) at 24 weeks. Secondary outcomes (comparing baseline with week 24) were the proportion of participants gaining or losing ≥ 15 ETDRS BCVA letters; area under the ETDRS BCVA over time curve; change in spectral-domain OCT (SD-OCT) central subfield thickness; and change in intraretinal fluid and subretinal fluid on SD-OCT.
Of 366 participants recruited from December 1, 2017, to November 30, 2018, 122, 123, and 121 were randomized to 0.5 mg OPT-302, 2.0 mg OPT-302, and sham, respectively. Mean (± standard deviation) visual acuity gain in the 2.0 mg OPT-302 group was significantly superior to sham (+14.2 ± 11.61 vs. +10.8 ± 11.52 letters; P = 0.01). The 0.5 mg OPT-302 group was not significantly different than the sham group (+9.44 ± 11.32 letters; P = 0.83). Compared with sham, the secondary BCVA outcomes favored the 2.0 mg OPT-302 group, with structural outcomes favoring both OPT-302 dosage groups. Adverse events (AEs) were similar across groups, with 16 (13.3%), 7 (5.6%), and 10 (8.3%) participants in the lower-dose, higher-dose, and sham groups, respectively, developing at least 1 serious AE. Two unrelated deaths both occurred in the sham arm.
Significantly superior vision gain was observed with OPT-302 2.0 mg combination therapy, versus standard of care, with favorable safety (ClinicalTrials.gov identifier: NCT03345082).
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