Background and Objectives

The emergence of resistant strains of Cutibacterium acnes can limit the efficacy of currently approved antibiotics for acne. VB-1953 is a next-generation antibiotic that exerts a bactericidal effect on resistant C. acnes. In this study, we investigated the safety, tolerability, and efficacy of VB-1953 topical gel in patients with moderate to severe acne having clindamycin-resistant C. acnes.

Methods

An investigator-initiated, open label, single-arm clinical study was conducted in patients with moderate to severe facial acne vulgaris showing poor or no response to previous clindamycin treatment. Nineteen subjects were enrolled in the study based on laboratory screening for the presence of clindamycin-resistant C. acnes in acne swab samples collected from patients. VB-1953 2% gel was applied on the entire face twice daily over 12 weeks. The primary efficacy endpoints were absolute changes in inflammatory and noninflammatory lesion counts from baseline at week 12, while the secondary efficacy endpoint was the proportion of subjects achieving Investigator Global Assessment success (score of 0 or 1) or a grade 2 or higher improvement from baseline at week 12. The presence and severity of local skin reactions (erythema, edema, scaling/dryness, burning/stinging, pruritus) were evaluated for safety. Additionally, the detection and quantification of drug-resistant C. acnes strains were performed in the laboratory using acne swab samples collected from patients.

Results

The occurrence of treatment-emergent adverse events or changes in vital signs, physical examinations, and urinalysis for any of the patients during the course of the entire study were clinically insignificant. Topical application of 2% VB-1953 topical gel resulted in a significant reduction of mean absolute inflammatory and noninflammatory lesion counts by 53.1% and 52.2%, respectively (p < 0.0001 for both), with an Investigator Global Assessment success of 26.3% at week 12 compared with baseline. Resistant bacteria were reduced by (94.3 ± 1%; p < 0.05) within 12 weeks of treatment with VB-1953.

Conclusion

These results indicate that VB-1953 topical gel can be a safe and effective therapy for moderate to severe acne with underlying resistant C. acnes in subjects who had not responded to previous antibiotic treatments.

中文翻译：

---

VB-1953外用凝胶剂在无反应性痤疮的耐克林霉素的角质层痤疮患者中的疗效和安全性。

背景和目标

痤疮皮肤杆菌耐药菌株的出现会限制目前批准的痤疮抗生素的功效。VB-1953是新一代抗生素，可对耐药的痤疮丙酸杆菌发挥杀菌作用。在这项研究中，我们调查了VB-1953外用凝胶剂在患有克林霉素耐药痤疮丙酸痤疮的中度至重度痤疮患者中的安全性，耐受性和疗效。

方法

研究人员发起的开放标签单臂临床研究是针对中度至重度寻常性痤疮表现出对先前克林霉素治疗不良或无反应的患者进行的。基于实验室筛查的耐氯林霉素痤疮丙酸杆菌的存在招募了19名受试者作为研究对象。从患者身上收集的痤疮拭子样本中。在12周内每天两次将VB-1953 2％凝胶涂在整个面部。主要功效终点是第12周时与基线相比炎症和非炎性病变计数的绝对变化，而次要功效终点是获得Investigator Global Assessment成功（分数为0或1）或与基线相比达到2级或更高水平的受试者比例在第12周时，评估了局部皮肤反应（红斑，浮肿，结垢/干燥，灼热/刺痛，瘙痒）的存在和严重程度，以评估安全性。此外，在实验室中使用从患者身上收集的痤疮拭子样本对耐药性痤疮丙酸杆菌菌株进行了检测和定量。

结果

在整个研究过程中，任何患者出现的治疗紧急不良事件或生命体征，体格检查和尿液分析的变化在临床上都是微不足道的。局部应用2％VB-1953局部凝胶可使平均绝对炎性和非炎性病变计数分别显着降低53.1％和52.2％（两种情况均p  <0.0001），《研究者全球评估》每周的成功率为26.3％与基线相比为12。 在用VB-1953治疗12周内，耐药菌减少了（94.3±1％；p <0.05）。

结论

这些结果表明，VB-1953局部凝胶剂可对以前对抗生素没有反应的受试者中度至重度痤疮并伴有潜在的痤疮丙酸杆菌，是一种安全有效的疗法。