Ehlers Justis P, Hu Allen, Boyer David, Cousins Scott W, Waheed Nadia K, Rosenfeld Philip J, Brown David, Kaiser Peter K, Abbruscato Anthony, Gao Gui, Heier Jeffrey
Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
Cumberland Valley Retina Consultants, Hagerstown, Maryland.
Ophthalmol Sci. 2024 Oct 9;5(1):100628. doi: 10.1016/j.xops.2024.100628. eCollection 2025 Jan-Feb.
This study evaluated the safety and efficacy of elamipretide in dry age-related macular degeneration (AMD) with noncentral geographic atrophy (GA).
ReCLAIM-2 was a prospective, phase II, randomized, placebo-controlled, double-masked, multicenter trial (NCT03891875).
Patients aged ≥55 years with ≥1 eye with dry AMD with GA were enrolled.
Administration of daily subcutaneous elamipretide 40 mg was investigated in subjects for 48 weeks followed by a 4-week follow-up period.
The primary efficacy end points were the mean change from baseline (BL) in low-luminance best-corrected visual acuity (LL BCVA) and the change in square root (Sqrt) converted GA area from BL as measured by OCT. Additional predefined end points included ellipsoid zone (EZ) integrity preservation assessment and categorical changes in LL BCVA. The primary safety end point was the incidence and severity of adverse events.
Of the 176 patients randomized, there were 117 and 59 patients in the elamipretide and placebo groups, respectively. Although elamipretide did not meet statistical significance for the primary end points (mean change in LL BCVA and mean change in Sqrt converted GA area), elamipretide produced a 43% reduction in the mean progression from BL in the macular percentage of total EZ attenuation/loss (i.e., complete loss of EZ band; nominal = 0.0034) and 47% reduction in the mean progression of macular percentage of partial EZ attenuation/degradation (i.e., EZ-retinal pigment endothelium thickness of ≤20 microns; nominal = 0.0040) versus placebo at week 48. Elamipretide treatment was also associated with significantly more patients experiencing a ≥10 letter gain in LL BCVA versus placebo (14.6% vs. 2.1%; nominal = 0.0404). Adverse events were reported in 86% of those receiving elamipretide and 71% of the placebo group with the most common events being injection site reactions (e.g., pruritus, injection site pain, bruising, and erythema).
While the primary end points were not met in this phase II study, elamipretide treatment was associated with a slowing of progressive EZ degradation/loss, a surrogate for photoreceptor damage. These findings have important clinical relevance since EZ attenuation/photoreceptor loss precedes and predicts the progressive pathological changes associated with vision loss and AMD. The EZ attenuation/loss end point will serve as the regulatory approved primary end point in the elamipretide phase III clinical development program.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
本研究评估了艾拉米肽在干性年龄相关性黄斑变性（AMD）合并非中心性地图样萎缩（GA）患者中的安全性和有效性。
ReCLAIM-2是一项前瞻性、II期、随机、安慰剂对照、双盲、多中心试验（NCT03891875）。
纳入年龄≥55岁、至少一只眼睛患有干性AMD合并GA的患者。
研究对象每日皮下注射40mg艾拉米肽，持续48周，随后进行4周的随访期。
主要疗效终点为低亮度最佳矫正视力（LL BCVA）相对于基线（BL）的平均变化，以及通过光学相干断层扫描（OCT）测量的从BL开始的平方根（Sqrt）转换GA面积的变化。其他预先定义的终点包括椭圆体带（EZ）完整性保存评估和LL BCVA的分类变化。主要安全性终点是不良事件的发生率和严重程度。
176例随机分组的患者中，艾拉米肽组和安慰剂组分别有117例和59例。尽管艾拉米肽在主要终点（LL BCVA的平均变化和Sqrt转换GA面积的平均变化）上未达到统计学显著性，但在第48周时，与安慰剂相比，艾拉米肽使黄斑区EZ总衰减/丧失百分比（即EZ带完全丧失；名义值=0.0034）从BL开始的平均进展降低了43%，使黄斑区部分EZ衰减/降解百分比（即EZ-视网膜色素上皮厚度≤20微米；名义值=0.0040）的平均进展降低了47%。与安慰剂相比，接受艾拉米肽治疗的患者中LL BCVA提高≥10字母的比例也显著更高（14.6%对2.1%；名义值=0.0404）。接受艾拉米肽治疗的患者中有86%报告了不良事件，安慰剂组为71%，最常见的事件是注射部位反应（如瘙痒、注射部位疼痛、瘀伤和红斑）。
虽然在这项II期研究中未达到主要终点，但艾拉米肽治疗与EZ渐进性降解/丧失的减缓相关，EZ渐进性降解/丧失是光感受器损伤的替代指标。这些发现具有重要的临床意义，因为EZ衰减/光感受器丧失先于并预测与视力丧失和AMD相关的渐进性病理变化。EZ衰减/丧失终点将作为艾拉米肽III期临床开发项目中监管部门批准的主要终点。
本文末尾的脚注和披露中可能会发现专有或商业披露信息。
