Lu Yingyi, Yu Xiaobing, Chen Youxin, Wu Chan, Jiang Qin, Ha Shaoping, Zhu Dan, Bi Yanlong, Liu Xiaoling, Zhang Han, Li Zhuo, Wang Wenxiang, Li Lin, Chen He, Zhang Yifan, Dai Hong, Fang Jianmin
Department of Ophthalmology, Institute of Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, 100730, China.
Department of Ophthalmology, Union Medical College Hospital, Chinese Academy of Medical Sciences, PekingBeijing, China.
Ophthalmol Ther. 2024 Sep;13(9):2405-2415. doi: 10.1007/s40123-024-00994-z. Epub 2024 Jul 20.
To assess the safety and efficacy of repeated intravitreal injections of RC28-E, a novel bispecific antibody that simultaneously binds vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with neovascular age-related macular degeneration (AMD). This was a prospective, multicenter, open-label clinical trial; 37 patients with choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) letter scores between 73 and 34 were enrolled.
Treatment regimens consisted of a 3-month loading phase and a pro re nata (PRN) maintenance phase. This study included three treatment groups: the 0.5, 1.0, and 2.0 mg RC28-E groups, with escalating doses ranging from 0.5 to 2.0 mg. Patients were evaluated monthly for 48 weeks. Safety was assessed based on ocular and systemic adverse events (AEs), pharmacokinetic characteristics, and the presence of anti-RC28-E antibodies. Efficacy was assessed using the mean change in BCVA and central subfield thickness (CST) from baseline to week 48.
Most AEs were mild or moderate. The most common AE was a minor injection-related subconjunctival hemorrhage (16.2%). The AEs did not increase with dose or repeated injections. At week 48, mean improvements in BCVA from baseline in the 0.5, 1.0, and 2.0 mg groups were 6.1 ± 8.3, 9.9 ± 10.7, and 7.6 ± 9.38 letters, respectively; mean reductions in CST in the three groups were 112.1 ± 160.5, 175.1 ± 212.4, and 128.7 ± 145.8 μm, respectively. The serum RC28-E concentrations in 95% of the patients were below the quantification limit of the assay. No significant change from baseline was observed in the mean plasma concentrations of VEGF or FGF over the 48 weeks of treatment. Pre-treatment antibodies to RC28-E were detected in 1 of the 37 patients. Antibodies to RC28-E were detected in two patients after dosing with RC28-E for 48 weeks.
RC28-E was well tolerated and exhibited an overall favorable safety profile with evidence of improvements in BCVA and anatomical parameters.
评估重复玻璃体内注射RC28-E（一种同时结合血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）的新型双特异性抗体）在新生血管性年龄相关性黄斑变性（AMD）患者中的安全性和有效性。这是一项前瞻性、多中心、开放标签的临床试验；纳入了37例继发于AMD且最佳矫正视力（BCVA）字母评分在73至34之间的脉络膜新生血管患者。
治疗方案包括3个月的负荷期和按需（PRN）维持期。本研究包括三个治疗组：0.5、1.0和2.0mg RC28-E组，剂量递增范围为0.5至2.0mg。患者进行了48周的每月评估。根据眼部和全身不良事件（AE）、药代动力学特征以及抗RC28-E抗体的存在情况评估安全性。使用从基线到第48周BCVA和中心子野厚度（CST）的平均变化评估疗效。
大多数AE为轻度或中度。最常见的AE是轻微的注射相关结膜下出血（16.2%）。AE并未随剂量或重复注射而增加。在第48周时，0.5、1.0和2.0mg组BCVA相对于基线的平均改善分别为6.1±8.3、9.9±10.7和7.6±9.38个字母；三组CST的平均降低分别为112.1±160.5、175.1±212.4和128.7±145.8μm。95%患者的血清RC28-E浓度低于检测的定量限。在48周的治疗期间，VEGF或FGF的平均血浆浓度与基线相比未观察到显著变化。37例患者中有1例在治疗前检测到抗RC28-E抗体。在使用RC28-E给药48周后，有2例患者检测到抗RC28-E抗体。
RC28-E耐受性良好，总体安全性良好，有证据表明BCVA和解剖学参数有所改善。
