A single-arm, open-label, multicenter Phase 2 safety and efficacy study evaluated patients with severe LC-FAOD evidenced by ongoing related musculoskeletal, cardiac, and/or hepatic events despite treatment. After a four-week run-in on current regimen, investigational triheptanoin (UX007) was titrated to a target dose of 25-35% of total daily caloric intake. Patients were evaluated on several age/condition-eligible endpoints, including submaximal exercise tests to assess muscle function/endurance (12-minute walk test; 12MWT) and exercise tolerance (cycle ergometry), and health related quality of life (HR-QoL). Results through 24weeks of treatment are presented; total study duration is 78weeks.
Twenty-nine patients (0.8 to 58years) were enrolled; most qualified based on severe musculoskeletal disease. Twenty-five patients (86%) completed the 24-week treatment period. At Week 18, eligible patients (n=8) demonstrated a 28% increase (LS mean=+181.9 meters; p=0.087) from baseline (673.4meters) in 12MWT distance. At Week 24, eligible patients (n=7) showed a 60% increase in watts generated (LS mean=+409.3W; p=0.149) over baseline (744.6W) for the exercise tolerance test. Improvements in exercise tests were supported by significant improvements from baseline in the adult (n=5) self-reported SF-12v2 physical component summary score (LS mean=+8.9; p<0.001). No difference from baseline was seen in pediatric parent-reported (n=5) scores (SF-10) at Week 24. Eighteen patients (62%) had treatment-related adverse events, predominantly gastrointestinal (55%), mild-to-moderate in severity, similar to that seen with prior treatment with medium chain triglyceride (MCT) oil. One patient experienced a treatment-related serious adverse event of gastroenteritis. One patient discontinued from study due to diarrhea of moderate severity; the majority of patients (25/29; 86%) elected to continue treatment in the extension period.
In patients with severe LC-FAOD, UX007 interim study results demonstrated improved exercise endurance and tolerance, and were associated with positive changes in self-reported HR-QoL.
单臂,开放标签,多中心2期安全性和有效性研究评估了严重LC-FAOD患者的持续相关肌肉骨骼,心脏,和/或肝事件,尽管治疗。在对当前方案进行为期四周的磨合后,研究性三庚酸甘油酯(UX007)的目标剂量为每日总热量摄入的25-35%.对患者进行了几个符合年龄/条件的终点评估,包括亚最大运动测试,以评估肌肉功能/耐力(12分钟步行测试;12MWT)和运动耐量(周期测功),和健康相关的生活质量(HR-QoL)。提供了24周治疗的结果;总研究持续时间为78周。
29名患者(0.8至58岁)入选,最合格的患者是严重的肌肉骨骼疾病。25名患者(86%)完成了24周的治疗期。在第18周,合格的患者(n=8)在12MWT距离中显示从基线(673.4米)增加28%(LS平均值=+181.9米;p=0.087)。在第24周,对于运动耐量测试,合格的患者(n=7)显示产生的瓦特比基线(744.6W)增加60%(LS平均值=+409.3W;p=0.149)。运动测试的改善得到了成人(n=5)自我报告的SF-12v2身体成分汇总评分(LS平均值=8.9;p<0.001)的显着改善。在第24周,在儿科父母报告的(n=5)评分(SF-10)中没有观察到与基线的差异。18例患者(62%)有治疗相关的不良事件,主要是胃肠道(55%),严重程度为轻度至中度,与以前用中链甘油三酯(MCT)油处理时看到的相似。一名患者经历了与治疗相关的严重不良事件胃肠炎。一名患者因中度腹泻而停止研究;大多数患者(25/29;86%)选择在延长期内继续治疗。
重度LC-FAOD患者,UX007中期研究结果表明,运动耐力和耐力得到了改善,并与自我报告的HR-QoL的积极变化相关。