Gao Yunxia, Lu Fang, Li Xiaoxin, Dai Hong, Liu Kun, Liu Xiaoling, Sun Zuhua, Xiang Jin, Ding Lieming, Liang Chris, Wang Yang, Shen Zhilin, Zhang Ming
Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.
Department of Ophthalmology, People Eye Center of People's Hospital, Peking University, Beijing, China.
Eye (Lond). 2023 Oct;37(15):3228-3233. doi: 10.1038/s41433-023-02496-x. Epub 2023 Apr 11.
To evaluate the efficacy and safety of oral vorolanib for the treatment of neovascular (wet) age-related macular degeneration (nAMD).
In the dose escalation, participants received ascending doses of oral vorolanib (25-100 mg daily). In the dose expansion, participants received recommended doses (25 and 50 mg daily).
Between March 15, 2015, and January 23, 2019, 41 participants were enrolled in 6 centres in China. At the data cut-off (November 14, 2019), two dose-limiting toxicities (DLTs) were observed during dose escalation (one in the 75 mg cohort and one in the 100 mg cohort). The maximum tolerated dose was not reached. Treatment-related adverse events (TRAEs) occurred in 33 (80.5%) participants, and grade 3 or higher TRAEs occurred in 12 (29.3%) participants. No fatal TRAEs were observed. Increases in the mean best-corrected visual acuity (BCVA) from baseline to Day 360 of +7.7 letters (range, -5-29; n = 41) were observed in participants who were administered vorolanib. Corresponding reductions in mean central subfield thickness (CST) and choroidal neovascularization (CNV) area at Day 360 were observed in these three groups.
Oral administration of vorolanib improved visual outcomes in participants with nAMD with manageable systemic safety profiles.
评估口服沃罗替尼治疗新生血管性（湿性）年龄相关性黄斑变性（nAMD）的疗效和安全性。
在剂量递增阶段，参与者接受递增剂量的口服沃罗替尼（每日25 - 100毫克）。在剂量扩展阶段，参与者接受推荐剂量（每日25毫克和50毫克）。
2015年3月15日至2019年1月23日期间，41名参与者在中国6个中心入组。在数据截止时（2019年11月14日），剂量递增期间观察到2例剂量限制性毒性（DLT）（75毫克队列1例，100毫克队列1例）。未达到最大耐受剂量。33名（80.5%）参与者发生了与治疗相关的不良事件（TRAEs），12名（29.3%）参与者发生了3级或更高等级的TRAEs。未观察到致命的TRAEs。接受沃罗替尼治疗的参与者从基线到第360天的平均最佳矫正视力（BCVA）增加了7.7个字母（范围，-5 - 29；n = 41）。在这三组中观察到第360天平均中心子场厚度（CST）和脉络膜新生血管（CNV）面积相应减少。
口服沃罗替尼可改善nAMD参与者的视力结果，且全身安全性可控。
