目的:本研究的目的是评估安全性,耐受性,以及在Leber遗传性视神经病变(LHON)患者中局部应用埃米普肽的潜在疗效。
方法:此阶段2,前瞻性,随机化,车辆控制,单中心临床试验涉及在52周的双盲治疗期(DMTP)内对LHON患者施用埃米普肽(MTP-131)局部眼用溶液,然后是开放延伸标签(OLE)长达108周的额外治疗。
方法:本研究包括12名LHON患者。年龄在18至50岁之间的患者视力下降,至少一年,不超过十年,基因证实的m.11778G>ALHON的诊断符合本试验的条件。
方法:在研究的前52周,患者被随机分为两组,两只眼睛都有依拉米肽,一只眼睛有依拉米肽,另一只眼睛有载体,随后是OLE,两只眼睛都用依拉米肽治疗。
方法:主要结果指标是对1%局部应用埃米普肽的不良事件的评估,主要疗效终点是最佳矫正视力(BCVA)的变化。次要结果指标包括色觉变化,视野平均偏差,和电生理结果。
结果:Elamipretide具有良好的耐受性,大多数因治疗引起的不良事件(TEAE)为轻度至中度并自发消退。在任何时间点,埃拉米肽治疗的眼睛中BCVA从基线的变化与载体眼睛没有显着差异。12名受试者中的6名符合临床相关益处(CRB)的标准。在事后分析中,与媒介物眼相比,埃拉米肽治疗眼的中央视野平均偏差相对于基线的变化明显更大.与基线相比,两个治疗组在OLE的颜色辨别和对比敏感度方面均有改善.
结论:Elamipretide治疗一般耐受性良好,未报告严重不良事件。虽然这项研究没有达到其主要的BCVA疗效终点,OLE期间视觉功能评估的改进,以及HVF中部地区的事后调查结果,令人鼓舞,需要进一步探索。
OBJECTIVE: This
study aimed to assess the safety, tolerability, and potential efficacy of topical elamipretide in patients affected with Leber hereditary optic neuropathy (LHON).
METHODS: This phase II, prospective, randomized, vehicle-controlled, single-center clinical
trial involved administration of elamipretide 1% topical ophthalmic solution to patients with LHON over a 52-week double-masked treatment period, followed by an open-label extension (OLE) for up to 108 additional weeks of treatment.
METHODS: Twelve patients with LHON were included in this
study. Patients aged 18 to 50 years with decreased vision for at least ≥ 1 year and ≤ 10 years, and a genetically confirmed diagnosis of m.11778G>A LHON were eligible for this
trial.
METHODS: For the first 52 weeks of the study, patients were randomized to 1 of 3 groups: elamipretide in both eyes or elamipretide in 1 eye (left eye and right eye were considered separate groups) and vehicle in the other eye, followed by an OLE in which both eyes were treated with elamipretide.
METHODS: The primary outcome measure was assessment of adverse events (AEs) from the administration of topical elamipretide, and the primary efficacy end point was change in best-corrected visual acuity (BCVA). Secondary outcome measures included changes in color vision, visual field mean deviation, and electrophysiological outcomes.
RESULTS: Elamipretide was well tolerated with the majority of AEs being mild to moderate and resolving spontaneously. The change from baseline in BCVA in elamipretide-treated eyes was not significantly different from the vehicle eyes at any time point. Six of 12 subjects met the criteria for clinically relevant benefit (CRB). In the post hoc analysis, change from baseline in mean deviation in the central visual field was significantly greater in elamipretide-treated eyes versus the vehicle eyes. Compared with baseline, both treatment groups showed improvement in color discrimination and contrast sensitivity in the OLE.
CONCLUSIONS: Elamipretide treatment was generally well tolerated, with no serious AEs reported. Although this
study did not meet its primary BCVA efficacy end point, improvements across assessments on visual function during the OLE and the post hoc findings of the Humphrey automated visual field central region were encouraging and require further exploration.
BACKGROUND: The author(s) have no proprietary or commercial interest in any materials discussed in this article.