目标:评估生物仿制药阿柏西普的非劣效性(CinnaGenCompany,伊朗)(P041)给发起人aflibercept(Regeneron,美国)(AFL)在疗效方面,安全,和免疫原性。
方法:这是一个阶段,52周,多中心,随机化,双面蒙面,和以1:1比例涉及眼睛的主动对照试验。
方法:继发于年龄相关性黄斑变性的活动性中央凹下脉络膜新生血管的患者随机分为P041和AFL两组。
方法:患者每4周注射一次阿柏西普,共3剂,随后每8周给药,直到第48周。
方法:主要结果是第52周时眼睛维持视力的非劣效性分析。次要结果包括视力(VA)和视网膜厚度的变化,安全评价,以及研究过程中的免疫原性。
结果:总计,纳入168例患者的168只眼。在第52周,P041中保持视力的患者比例为94.44%,而AFL组为94.52%。维持视力与基线的差异的95%置信区间(CI)未超过10%的预定义非劣效性界限(p值:0.98,95%CI,-0.0008(-0.074,0.074))。次要结果显示两组结果相似(所有p值>0.05)。两个研究组之间的安全性测量结果和免疫原性相似。
结论:P041在n-AMD眼中不劣于AFL。其他功效和安全性发现也表明两种产品的相似性。
OBJECTIVE: To assess the noninferiority of biosimilar aflibercept (P041, CinnaGen) to the originator aflibercept (AFL, Regeneron) in terms of efficacy, safety, and immunogenicity.
METHODS: This was a phase Ш, 52-week, multicenter, randomized, double-masked, and active control trial involving eyes in a 1:1 ratio.
METHODS: Patients with active subfoveal choroidal neovascularization secondary to age-related macular degeneration randomized into the 2 groups of P041 and AFL.
METHODS: Patients received an injection of aflibercept every 4 weeks for 3 doses, followed by administration every 8 weeks up to week 48.
METHODS: The primary outcome was the noninferiority analysis of eyes maintaining vision at week 52. Secondary outcomes included the changes in visual acuity and retinal thickness, safety evaluation, and immunogenicity during the study.
RESULTS: In total, 168 eyes of 168 patients were included. At week 52, the proportion of patients maintaining vision was 94.44% in the P041 group compared with 94.52% in the AFL group. The 95% confidence interval (CI) for the difference of maintaining vision from baseline did not exceed the predefined noninferiority margin of 10% (difference, -0.0008; 95% CI, -0.074 to 0.074; P = 0.98). Secondary outcomes indicated similar results in both arms (all P > 0.05). Safety measured outcomes and immunogenicity were similar between the 2 study groups.
CONCLUSIONS: Biosimilar aflibercept was noninferior to AFL in eyes with neovascular age-related macular degeneration. Other efficacy and safety findings also indicated the similarity of 2 products.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.