Telacebec, a Potent Agent in the Fight against Tuberculosis: Findings from a Randomized, Phase 2 Clinical Trial and Beyond.

Telacebec is a novel, first-in-class agent targeting mycobacterial cellular energy production in a range of pathogenic mycobacteria, including Mycobacterium tuberculosis, M. leprae, and M. ulcerans.

Telacebec是一种新型的一类新药，针对包括结核分枝杆菌、麻风分枝杆菌和溃疡分枝杆菌等多种致病性分枝杆菌的细胞能量产生进行靶向作用。

Objectives: To explore telacebec's early bactericidal activity, tolerability, safety, and pharmacokinetics in patients with pulmonary tuberculosis and to summarize its current state of development for other diseases.

目的：探讨telacebec在肺结核患者中的早期杀菌活性、耐受性、安全性和药代动力学，并总结其在其他疾病中的当前开发状态。

Methods: We randomly assigned 64 patients with smear-positive, drug-sensitive tuberculosis to daily telacebec 100, 200, or 300 mg, or standard four-drug treatment as control, for 14 days.

方法：我们随机分配了64名涂片阳性的药物敏感性结核病患者，分别接受每日100、200或300毫克的telacebec治疗，或作为对照的标准四药治疗，持续14天。

Measurements and Main Results: Sputum collected overnight was cultured in liquid and on solid media to determine the change of viable mycobacteria over time.

测量和主要结果：夜间收集的痰液在液体和固体培养基上进行培养，以确定活结核菌随时间的变化。

Safety and tolerability were assessed daily.

安全性和耐受性每天进行评估。

A full pharmacokinetic profile was obtained on Day 14.

在第14天获得了完整的药物动力学资料。

We found a dose-dependent reduction of the sputum mycobacterial load with a mean ± SD daily change for telacebec 300 mg and control, respectively, of 0.097 ± 0.050 and 0.200 ± 0.073 log colony-forming units, and 3.738 ± 2.747 and 6.853 ± 1.194 hours to culture positivity over the first 14 days of treatment.

我们发现痰液中分枝杆菌负荷量与剂量呈依赖性减少，telacebec 300 mg和对照组的平均±标准差每日变化分别为0.097±0.050和0.200±0.073对数菌落形成单位，以及在治疗的前14天内，培养阳性的时间分别为3.738±2.747和6.853±1.194小时。

Pharmacokinetics were dose proportional. Telacebec was well tolerated and safe, with low adverse eventrates across all doses.

药代动力学呈剂量比例性。Telacebec耐受性良好且安全，各剂量下的不良事件率均较低。

Conclusions: These results confirm telacebec's clinical activity against M. tuberculosis.

结论：这些结果证实了telacebec对结核分枝杆菌的临床活性。

Longer trials, in combination with other agents, are required to validate these results and to investigate telacebec's full potential. These results encourage the exploration of telacebec for more effective, shorter treatment regimens for leprosy and Buruli ulcer.

需要更长时间的试验，结合其他药物，以验证这些结果并探索telacebec的全部潜力。这些结果鼓励对telacebec进行更有效的、疗程更短的麻风病和Buruli溃疡治疗方案的探索。

A clinical trial for Buruli ulcer is under way.

一项针对Buruli溃疡的临床试验正在进行中。

Clinical trial registered with URL (NCT03563599).

临床试验已通过网址(NCT03563599)注册。