目的:评估在TAZPOWER试验的开放标签扩展(OLE)期间埃拉米肽在Barth综合征(BTHS)患者中的长期疗效和安全性。
方法:TAZPOWER是一项为期28周的随机研究,双盲,安慰剂对照试验,然后是168周的OLE。进入OLE的患者继续每天皮下40mg依拉米肽。OLE主要终点是安全性和耐受性;次要终点包括6分钟步行测试(6MWT)和BarTH综合征症状评估(BTHS-SA)中的基线变化。肌肉力量,医生和患者评估的结果,超声心动图参数,和生物标志物,包括心磷脂(CL)和单心磷脂(MLCL),被评估。
结果:10名患者进入OLE;8名患者进入第168周就诊。Elamipretide耐受性良好,注射部位反应是最常见的不良事件。在所有OLE时间点(累积96.1米的改善[第168周,p=0.003]),在6MWT上从OLE基线显著改善。在所有OLE时间点,平均BTHS-SA总疲劳评分低于基线(改善)。3-D左心室卒中,舒张末期,收缩末期容积改善了,显示出从基线到第168周的显著改善趋势。MLCL/CL值显示改善,与重要的临床结果相关。
结论:Elamipretide与长期耐受性和疗效有关,改善BTHS的功能评估和心脏功能。
OBJECTIVE: Evaluate long-term efficacy and safety of elamipretide during the open-label extension (OLE) of the TAZPOWER trial in individuals with Barth syndrome (BTHS).
METHODS: TAZPOWER was a 28-week randomized, double-blind, and placebo-controlled trial followed by a 168-week OLE. Patients entering the OLE continued elamipretide 40 mg subcutaneous daily. OLE primary endpoints were safety and tolerability; secondary endpoints included change from baseline in the 6-minute walk test (6MWT) and BarTH Syndrome Symptom Assessment (BTHS-SA) Total Fatigue score. Muscle strength, physician- and patient-assessed outcomes, echocardiographic parameters, and biomarkers, including cardiolipin (CL) and monolysocardiolipin (MLCL), were assessed.
RESULTS: Ten patients entered the OLE; 8 reached the week 168 visit. Elamipretide was well tolerated, with injection-site reactions being the most common adverse events. Significant improvements from OLE baseline on 6MWT occurred at all OLE time points (cumulative 96.1 m of improvement [week 168, P = .003]). Mean BTHS-SA Total Fatigue scores were below baseline (improved) at all OLE time points. Three-dimensional (3D) left ventricular stroke, end-diastolic, and end-systolic volumes improved, showing significant trends for improvement from baseline to week 168. MLCL/CL values showed improvement, correlating to important clinical outcomes.
CONCLUSIONS: Elamipretide was associated with sustained long-term tolerability and efficacy, with improvements in functional assessments and cardiac function in BTHS.