RT期刊文章SR电子T1 Elamipretide疗效和安全性的主要线粒体肌病患者:MMPOWER-3随机临床试验摩根富林明神经病学神经学乔FD Lippincott Williams &威尔金斯10.1212 SP / WNL。首页0000000000207402 10.1212 / WNL。0000000000207402 A1阿梅尔Karaa A1恩里科·贝尔蒂尼A1 Valerio Carelli A1布鲁斯·H·科恩A1 Gregory m .新奥集团A1 Marni J福尔克A1艾米·戈尔茨坦A1 Grainne Siobhan Gorman A1理查德·哈斯A1渡Hirano A1托马斯Klopstock A1玫琳凯Koenig A1科妮莉亚Kornblum) A1 Costanza Lamperti A1雷曼A1尼古拉Longo A1安娜玛丽亚Judit Molnar A1苏米特•帕里克以A1汉Phan A1罗伯特D S Pitceathly A1罗素Saneto A1费尔南多Scaglia A1 Serenella Servidei A1马克线粒体A1安东尼奥Toscano A1约翰L。K范霍夫A1约翰vis A1杰瑞Vockley A1 Jeffrey S Finman A1大卫布朗A1詹姆斯Shiffer A1 Michelango曼库索A1 MMPOWER-3审判人员的年2023 UL //www.ez-admanager.com/content/early/2023/06/02/WNL.0000000000207402.abstract 首页AB背景和目标:主要线粒体肌病(PMMs)包含一组遗传疾病,损害线粒体氧化磷酸化,不利影响身体功能、运动能力、生活质量(QoL)。当前PMM护理解决症状,有限的临床影响,构成一个重要的治疗未满足的需求。我们从MMPOWER-3显示数据、关键阶段3,随机、双盲、安慰剂对照临床试验的有效性和安全性评估在参与者elamipretide genetically-confirmed PMM。方法:筛选后,合格的参与者被随机的1:1,24周接受elamipretide 40毫克/天或安慰剂皮下注射。主要疗效端点包括改变从基线到24周走在6分钟步行的距离测试(6 mwt),并在主节点上总疲劳线粒体肌病症状评估(PMMSA)。二次端点包括PMMSA最麻烦的症状评分、NeuroQoL疲劳短形式的分数,和病人,Clinician-Global PMM症状的印象。结果:参与者(N = 218)是随机的(N = 109 elamipretide;n = 109安慰剂)。平均年龄为45.6年(64%女性;94%的白人)。 The majority of participants (n=162 [74%]) had mitochondrial DNA (mtDNA) mutations, with the remainder having nuclear DNA (nDNA) defects. At screening, the most frequent bothersome PMM symptom on the PMMSA was tiredness during activities (28.9%). At baseline, mean distance walked on the 6MWT was 336.7±81.2 meters, mean score for Total Fatigue on the PMMSA was 10.6±2.5, and mean T-score for the Neuro-QoL Fatigue Short Form was 54.7±7.5. The study did not meet its primary endpoints assessing changes in the 6MWT and PMMSA Total Fatigue Score (TFS). Between the participants receiving elamipretide versus placebo, the difference in the Least Squares Mean (SE) from baseline to Week 24 on distance walked on the 6MWT was -3.2 (95% confidence interval,-18.7,12.3; p=0.69) meters and on the PMMSA Total Fatigue Score was -0.07 (95% confidence interval,-0.10,0.26; p=0.37). Elamipretide treatment was well-tolerated with most adverse events being mild to moderate in severity.Discussion: Subcutaneous elamipretide treatment did not improve outcomes in the 6MWT and PMMSA TFS in patients with PMM. However, this phase-3 study demonstrated that subcutaneous elamipretide is well-tolerated.Trial Registration Information: Trial registered with clinicaltrials.gov, Clinical Trials Identifier: NCT03323749; submitted on October 12, 2017;first patient enrolled October 9, 2017. https://clinicaltrials.gov/ct2/show/NCT03323749?term=elamipretide&draw=2&rank=9Classification of Evidence: This study provides Class I evidence that elamipretide does not improve the 6 minute walk test or fatigue at 24 weeks compared to placebo in patients with primary mitochondrial myopathy.

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