Zhang Wenfei, Cheng Shiyu, Gu Xingwang, Liu Xinyu, Dai Hong, Zhuang Wenjuan, Sun Bin, Gao Lei, Sun Xuguang, Zhang Ming, Song Zongming, Wang Wenxiang, Li Lin, Chen He, Fang Jianmin, Chen Youxin
Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Beijing Key Laboratory of Fundus Diseases Intelligent Diagnosis & Drug/Device Development and Translation, Beijing 100730, China.
Br J Ophthalmol. 2025 Jun 23;109(7):784-790. doi: 10.1136/bjo-2024-326006.
To compare different doses and dosing regimens of RC28-E, a novel bispecific antibody that simultaneously binds vascular endothelial growth factor-A (VEGF-A) and fibroblast growth factor-2 (FGF-2), with conbercept in patients with diabetic macular edema (DME).
Prospective, randomised, active comparator-controlled, open-label, multicentre, phase 2 clinical trial.cente PARTICIPANTS: The trial enrolled patients aged 18 years or older with centre-involving DME, best-corrected visual acuity (BCVA) of 73 to 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and central subfield thickness (CST) of 300 µm or more.
Patients were assigned randomly to one of five treatment regimens: 1.0 mg RC28-E for three initial monthly doses and then every 8 weeks (1.0mgQ8); 1.0 mg RC28-E for five initial monthly doses and then on a pro re nata (PRN) basis (1.0mgPRN); 2.0 mg RC28-E for three initial monthly doses and then every 8 weeks (2.0mgQ8); 2.0 mg RC28-E for five initial monthly doses and then on a PRN basis (2.0mgPRN); or 0.5 mg conbercept for three initial monthly doses and then on a PRN basis. Assessments were made at baseline and every 4 weeks thereafter.
The primary endpoint was the change in BCVA compared with baseline at 24 and 52 weeks. Secondary endpoints included the change in CST from baseline at 52 weeks; the proportion of patients who gained/lost ≥15 letters, ≥10 letters and >0 letter in BCVA; and the number of injections and safety outcomes.
The trial enrolled 156 patients. Mean improvements in BCVA in the RC28-E groups at week 24 were 7.1, 11.0, 7.4 and 10.5 letters for 1.0mgQ8, 1.0mgPRN, 2.0mgQ8 and 2.0mgPRN regimens, respectively, versus 9.7 letters for the conbercept group (p=0.146). By week 52, the RC28-E groups exhibited respective mean BCVA enhancements of 5.5, 9.5, 9.2 and 9.7 letters, compared with 8.4 letters of the conbercept group (p=0.469). Mean reductions in CST in the RC28-E groups at week 52 were -163.2 µm, -136.9 µm, -142.5 µm and -153.6 µm, versus -160.7 µm for the conbercept group (p=0.948). The Per Protocol Set analysis indicated that at 24 weeks, the BCVA improvement in the 2.0mgPRN group was significantly greater than that in the conbercept group (14.0 vs 9.8, p=0.019). In patients with poor baseline glycaemic control (HbA1c ≥7.5%), the 2.0mgPRN group showed greater BCVA improvement than the conbercept group (14.4 vs 4.2, p=0.039) at week 52. During the maintenance phase, the 2.0mgPRN group had fewer injections (2.8, 95% CI 1.8 to 3.7) compared with the conbercept group (4.4, 95% CI 3.5 to 5.2). RC28-E was generally well tolerated. The incidence of ocular adverse events in study eyes was comparable between RC28-E groups (22.6% in 1.0mgQ8 group, 26.7% in 1.0mgPRN group, 34.4% in 2.0mgQ8 group, 25.0% in 2.0 mg PRN group) and conbercept group (32.3%). The number of ocular serious adverse events was 1 (1.0mgQ8), 0 (1.0mgPRN), 1 (2.0mgQ8), 2 (2.0mgPRN) and 0 (conbercept).
Intravitreous RC28-E improved BCVA and CST in eyes with centre-involved DME. Compared with conbercept, the 2.0mgPRN regimen of RC28-E was recommended due to its superior efficacy in improving vision particularly for patients with poor glycaemic control, fewer treatment injections during the maintenance phase and comparable safety profile.
NCT04782115.
比较新型双特异性抗体RC28-E（可同时结合血管内皮生长因子-A（VEGF-A）和成纤维细胞生长因子-2（FGF-2））不同剂量和给药方案与康柏西普在糖尿病性黄斑水肿（DME）患者中的疗效。
前瞻性、随机、活性对照、开放标签、多中心2期临床试验。
该试验纳入了年龄在18岁及以上、患有累及中心凹的DME、最佳矫正视力（BCVA）为73至24个早期糖尿病性视网膜病变研究（ETDRS）字母、中心子野厚度（CST）为300μm或更高的患者。
患者被随机分配到五种治疗方案之一：初始三个月每月注射1.0mg RC28-E，之后每8周注射一次（1.0mgQ8）；初始五个月每月注射1.0mg RC28-E，之后按需注射（1.0mgPRN）；初始三个月每月注射2.0mg RC28-E，之后每8周注射一次（2.0mgQ8）；初始五个月每月注射2.0mg RC28-E，之后按需注射（2.0mgPRN）；或初始三个月每月注射0.5mg康柏西普，之后按需注射。在基线期及之后每4周进行评估。
主要终点是24周和52周时与基线相比的BCVA变化。次要终点包括52周时与基线相比的CST变化；BCVA增加/减少≥15个字母、≥10个字母和>0个字母的患者比例；以及注射次数和安全性结果。
该试验共纳入156例患者。在第24周时，1.0mgQ8、1.0mgPRN、2.0mgQ8和2.0mgPRN方案的RC28-E组BCVA平均改善分别为7.1、11.0、7.4和10.5个字母，而康柏西普组为9.7个字母（p = 0.146）。到第52周时，RC28-E组的BCVA平均改善分别为5.5、9.5、9.2和9.7个字母，而康柏西普组为8.4个字母（p = 0.469）。在第52周时，RC28-E组的CST平均降低分别为-163.2μm、-136.9μm、-142.5μm和-153.6μm，而康柏西普组为-160.7μm（p = 0.948）。符合方案集分析表明，在24周时，2.0mgPRN组的BCVA改善显著大于康柏西普组（14.0对9.8，p = 0.019）。在基线血糖控制不佳（糖化血红蛋白≥7.5%）的患者中，在第52周时，2.0mgPRN组的BCVA改善大于康柏西普组（14.4对4.2，p = 0.039）。在维持阶段，2.0mgPRN组的注射次数（2.8，95%CI 1.8至3.7）少于康柏西普组（4.4，95%CI 3.5至5.2）。RC28-E总体耐受性良好。RC28-E组（1.0mgQ8组为22.6%，1.0mgPRN组为26.7%，2.0mgQ8组为34.4%，2.0mgPRN组为25.0%）和康柏西普组（32.3%）研究眼的眼部不良事件发生率相当。眼部严重不良事件的数量分别为1例（1.0mgQ8）、0例（1.0mgPRN）、1例（2.0mgQ8）、2例（2.0mgPRN）和0例（康柏西普）。
玻璃体内注射RC28-E可改善累及中心凹的DME患者的BCVA和CST。与康柏西普相比，推荐RC28-E的2.0mgPRN方案，因为其在改善视力方面疗效更优，尤其对于血糖控制不佳的患者，在维持阶段治疗注射次数更少且安全性相当。
NCT04782115。
