Purpose

To evaluate effectiveness of elamipretide in Barth syndrome (BTHS), a genetic condition of defects in TAZ, which causes abnormal cardiolipin on the inner mitochondrial membrane.

Methods

We performed a randomized, double-blind, placebo-controlled crossover trial followed by an open-label extension in BTHS to test the effect of elamipretide, a mitochondrial tetrapeptide that interacts with cardiolipin. In part 1, 12 subjects were randomized to 40 mg per day of elamipretide or placebo for 12 weeks, followed by a 4-week washout and then 12 weeks on the opposite arm. Ten subjects continued on the open-label extension (part 2) of 40 mg per day of elamipretide, with eight subjects reaching 36 weeks. Primary endpoints were improvement on the 6-minute walk test (6MWT) and improvement on a BTHS Symptom Assessment (BTHS-SA) scale.

Results

In part 1 neither primary endpoint was met. At 36 weeks in part 2, there were significant improvements in 6MWT (+95.9 m, p = 0.024) and BTHS-SA (-2.1 points, p = 0.031). There were also significant improvements in secondary endpoints including knee extensor strength, patient global impression of symptoms, and some cardiac parameters.

Conclusion

In this interventional clinical trial in BTHS, daily administration of elamipretide led to improvement in BTHS symptoms.

中文翻译：

---

一项 2/3 期随机临床试验，随后是一项开放标签扩展，以评估 elamipretide 在 Barth 综合征（一种线粒体心磷脂代谢的遗传性疾病）中的有效性

目的

评估 elamipretide 在 Barth 综合征 (BTHS) 中的有效性，BTHS 是一种TAZ缺陷的遗传病，会导致线粒体内膜上的心磷脂异常。

方法

我们进行了一项随机、双盲、安慰剂对照的交叉试验，随后在 BTHS 中进行了开放标签扩展，以测试 elamipretide（一种与心磷脂相互作用的线粒体四肽）的作用。在第 1 部分中，12 名受试者被随机分配到每天 40 mg 的 elamipretide 或安慰剂组，持续 12 周，然后进行 4 周的冲洗，然后在另一臂上使用 12 周。10 名受试者继续接受每天 40 毫克 elamipretide 的开放标签延长（第 2 部分），其中 8 名受试者达到 36 周。主要终点是 6 分钟步行测试 (6MWT) 的改善和 BTHS 症状评估 (BTHS-SA) 量表的改善。

结果

在第 1 部分中，两个主要终点均未达到。在第 2 部分的第 36 周时，6MWT（+95.9 m，p  = 0.024）和 BTHS-SA（-2.1 分，p  = 0.031）有显着改善。次要终点也有显着改善，包括膝关节伸肌强度、患者对症状的总体印象和一些心脏参数。

结论

在这项 BTHS 的介入性临床试验中，每天服用 elamipretide 可改善 BTHS 症状。