雷戈非尼滴眼液治疗新生血管性年龄相关性黄斑变性（DREAM）的开发研究：一项开放标签的 II 期临床试验。
The Developing Regorafenib Eye drops for neovascular Age-related Macular degeneration (DREAM) study: an open-label phase II trial.
机构信息
Department of Ophthalmology, Charité - University Medicine Berlin, Berlin, Germany.
Bern Photographic Reading Center and Department of Ophthalmology, Inselspital, University Hospital, University of Bern, Bern, Switzerland.
出版信息
Br J Clin Pharmacol. 2019 Feb;85(2):347-355. doi: 10.1111/bcp.13794. Epub 2018 Nov 25.
AIMS
This programme investigated topical regorafenib, a multikinase inhibitor, in patients with neovascular age-related macular degeneration (nAMD).
METHODS
Topical regorafenib was investigated in an open-label, phase IIa/b study in which patients with choroidal neovascularization (CNV) secondary to nAMD received regorafenib (25 μl, 30 mg ml ) three times a day for 12 weeks. The primary endpoint of the phase II/a/b study was mean change in best-corrected visual acuity (BCVA) from baseline to weeks 4 and 12.
RESULTS
In nAMD patients (N = 51), mean changes in BCVA were +1.2 [90% confidence interval (CI) -0.61, 2.97] and -2.4 (90% CI -4.18, -0.54) letters at weeks 4 and 12, respectively. Ocular treatment-emergent adverse events (TEAEs) (study eye) were reported in 21 patients by week 12. There was one serious ocular TEAE (visual acuity reduced) that was not drug related. Twenty patients required rescue (intravitreal ranibizumab).
CONCLUSIONS
The programme was terminated after phase IIa ended because efficacy was lower than with current nAMD treatments. According to elaborate post hoc analyses, the most likely reason was insufficient exposure in the target compartment (back of the eye).
目的
本研究旨在评估多激酶抑制剂雷戈非尼（regorafenib）局部给药治疗新生血管性年龄相关性黄斑变性（nAMD）的疗效。
方法
在一项开放性、Ⅱa/Ⅱb 期临床试验中，研究人员对继发于 nAMD 的脉络膜新生血管（CNV）患者进行了雷戈非尼（regorafenib）治疗。患者每日 3 次、每次滴注 25 μl（浓度为 30mg/ml），疗程为 12 周。Ⅱa/Ⅱb 期研究的主要终点为从基线至第 4 周和第 12 周时最佳矫正视力（BCVA）的平均变化。
结果
在 nAMD 患者（N=51）中，第 4 周和第 12 周时 BCVA 的平均变化分别为+1.2 个字母（90%置信区间[CI]：-0.61，2.97）和-2.4 个字母（90%CI：-4.18，-0.54）。第 12 周时，21 例患者报告了眼部治疗出现的不良事件（study eye）。有 1 例严重眼部不良事件（视力下降）与药物无关。20 例患者需要进行挽救性治疗（玻璃体内注射 ranibizumab）。
结论
由于疗效低于当前 nAMD 治疗方法，Ⅱa 期结束后该研究即被终止。根据详细的事后分析，最有可能的原因是目标部位（眼后）的药物暴露不足。
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