A phase 2 placebo-controlled clinical trial with ACU-4429 (visual cycle modulator) for the treatment of dry age related macular degeneration (AMD): effect on drusen volume, measured with an optical coherence tomography device and a newly developed algorit

使用 ACU-4429（视觉周期调节剂）治疗干性年龄相关性黄斑变性 (AMD) 的 2 期安慰剂对照临床试验：对玻璃疣体积的影响，使用光学相干断层扫描设备和新开发的算法进行测量

• 批准号: 242255480
• 负责人: Dr. Karen Schaal
• 金额: --
• 依托单位: Bascom Palmer Eye Institute
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/242255480?language=en
• 关键词: phase; placebo; controlled; clinical; trial

The intention of the presented research project is to find a treatment for non-exudative (dry) Age Related Macular Degeneration (AMD), which is currently not treatable, in contrast to the wet form of the disease. AMD is a chronic degenerative retinal disease and the leading cause of blindness in the elderly (over 50 years of age) of the industrialized world. Dry AMD affects approx. 90 % of all AMD-patients, who so far do not have a therapeutic option. The goal of my research project is to initiate a placebo-controlled phase 2 clinical trial with ACU-4429 (visual cycle modulator) as oral medication for the treatment of dry AMD and its effect on drusen growth as drusen are first signs of AMD. ACU-4429 is an isomerase-complex (RPE-65)-inhibitor, and a first phase 1 clinical trial on healthy subjects showed an effect on the accumulation of toxic end-products in the retinal pigment epithelial cell (RPE). ACU-4429 could therefore affect the development of drusen, and influence the course of the disease. Drusen volume is an important endpoint of the presented study and is measured with a newly developped algorithm incorporated in the Cirrus spectral domain optical coherence tomography device (SD-OCT). This algorithm generates a difference map between the real RPE of a patient and a virtuell RPE (free of any deformation), resulting in a drusen-volume map. Considering natural drusen dynamic, an effect of ACU-4429 on drusen growth (sign for disease progression) can be measured with this algorithm. The hypothesis of the project is to stop or at least to retard dry AMD progression with ACU-4429 medication.

本研究项目的目的是寻找一种治疗非渗出性（干性）年龄相关性黄斑变性（AMD）的方法，与湿性形式的疾病相比，目前这种方法无法治疗。AMD是一种慢性退行性视网膜疾病，是工业化国家老年人（50岁以上）失明的主要原因。干性AMD影响约。90%的AMD患者目前没有治疗选择。我的研究项目的目标是启动一项安慰剂对照的2期临床试验，使用ACU-4429（视觉周期调节剂）作为治疗干性AMD的口服药物及其对玻璃疣生长的影响，因为玻璃疣是AMD的第一个迹象。ACU-4429是一种异构酶复合物（RPE-65）抑制剂，在健康受试者中进行的第一项1期临床试验显示了对视网膜色素上皮细胞（RPE）中毒性终产物积累的影响。因此，ACU-4429可以影响玻璃疣的发展，并影响疾病的进程。玻璃疣体积是本研究的一个重要终点，采用Cirrus光谱域光学相干断层扫描仪（SD-OCT）中新开发的算法进行测量。该算法生成患者的真实的RPE与虚拟RPE（无任何变形）之间的差异图，从而产生玻璃疣体积图。考虑到天然玻璃疣动态，可以用该算法测量ACU-4429对玻璃疣生长（疾病进展的迹象）的影响。该项目的假设是用ACU-4429药物停止或至少延缓干性AMD进展。