未经评估:为了评估安全性,耐受性,对患有中年相关性黄斑变性(AMD)和高危玻璃疣(HRD)的患者皮下给予线粒体靶向药物埃拉米肽的可行性,并对视觉功能变化进行探索性分析。
未经评估:第一阶段,单中心,开放标签,预先计划的HRD队列的24周临床试验。
UNASSIGNED:年龄≥55岁的中度AMD和HRD成人患者。
UNASSIGNED:参与者每天接受皮下依拉米肽40毫克,在整个研究过程中评估安全性和耐受性。眼部评估包括正常亮度最佳矫正视力(BCVA),低亮度最佳矫正视力(LLVA),正常亮度双眼阅读敏锐度(NLRA),低亮度双眼阅读敏锐度(LLRA),谱域OCT,眼底自发荧光(FAF),介孔显微视野,暗适应,和低亮度问卷(LLQ)。
未经评估:主要终点是安全性和耐受性。预先确定的探索性终点包括BCVA相对于基线的变化,LLVA,NLRA,LLRA,视网膜色素上皮(RPE)-玻璃疣复合物(DC)体积通过OCT,FAF,介孔显微视野,暗适应,和LLQ结果。
未经批准:依拉米肽的皮下给药是非常可行的。所有患有HRD的参与者(n=21)经历了1个或更多不良事件(AE),但都是轻度(57%)或中度(43%),最常见的事件与注射部位反应有关。未发生严重的系统性AE。一名参与者因注射部位反应而停药,1名参与者退出,因为他们不希望继续研究访问,1名参与者在经历一过性视力障碍后退出。在完成这项研究的18名参与者中,BCVA从基线至24周的平均变化为+3.6个字母(P=0.014),LLVA为+5.6个字母(P=0.004).与基线相比,平均NLRA提高了最小分辨率角(logMAR)单位的-0.11对数(P=0.001),LLRA为-0.28logMAR单位(P<0.0001)。在LLQ的7个分量表中的6个中发现了显着改善(P<0.0015)。RPE-DC体积没有观察到显著变化,FAF,介孔显微视野,或黑暗适应。
未经证实:Elamipretide在治疗中度AMD和HRD时似乎通常是安全且耐受性良好的。探索性分析表明对视觉功能有积极的影响,特别是在低亮度条件下。有必要进一步研究埃拉米肽治疗中度AMD伴HRD。
UNASSIGNED: To assess safety, tolerability, and feasibility of subcutaneous administration of the mitochondrial-targeted drug elamipretide in patients with intermediate age-related macular degeneration (AMD) and high-risk drusen (HRD) and to perform exploratory analyses of change in visual function.
UNASSIGNED: Phase 1, single-center, open-label, 24-week clinical
trial with preplanned HRD cohort.
UNASSIGNED: Adult patients ≥55 years of age with intermediate AMD and HRD.
UNASSIGNED: Participants received subcutaneous elamipretide 40 mg daily, with safety and tolerability assessed throughout the
study. Ocular assessments included normal-luminance best-corrected visual acuity (BCVA), low-luminance best-corrected visual acuity (LLVA), normal-luminance binocular reading acuity (NLRA), low-luminance binocular reading acuity (LLRA), spectral-domain OCT, fundus autofluorescence (FAF), mesopic microperimetry, dark adaptation, and low-luminance questionnaire (LLQ).
UNASSIGNED: The primary end point was safety and tolerability. Prespecified exploratory end points included changes from baseline in BCVA, LLVA, NLRA, LLRA, retinal pigment epithelium (RPE)-drusen complex (DC) volume by OCT, FAF, mesopic microperimetry, dark adaptation, and LLQ results.
UNASSIGNED: Subcutaneous administration of elamipretide was highly feasible. All participants with HRD (n = 21) experienced 1 or more adverse events (AEs), but all were mild (57%) or moderate (43%), with the most common events related to injection site reactions. No serious systemic AEs occurred. One participant discontinued because of injection site reaction, 1 participant withdrew because they did not wish to continue
study visits, and 1 participant withdrew after experiencing transient visual impairment. Among the 18 participants who completed the
study, mean change in BCVA from baseline to 24 weeks was +3.6 letters (P = 0.014) and LLVA was +5.6 letters (P = 0.004). Compared with baseline, mean NLRA improved by -0.11 logarithm of the minimum angle of resolution (logMAR) units (P = 0.001), and LLRA by -0.28 logMAR units (P < 0.0001). Significant improvements were found in 6 of 7 subscales of the LLQ (P <0.0015). No significant changes were observed for RPE-DC volume, FAF, mesopic microperimetry, or dark adaptation.
UNASSIGNED: Elamipretide appeared to be generally safe and well tolerated in treating intermediate AMD and HRD. Exploratory analyses demonstrate a positive effect on visual function, particularly under low-luminance conditions. Further
study of elamipretide for treatment of intermediate AMD with HRD is warranted.