Randomized double-blind study on safety and tolerability of TP-102 phage cocktail in patients with infected and non-infected diabetic foot ulcers.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2025-05-09 Epub Date: 2024-12-30 DOI:10.1016/j.medj.2024.11.018

Ran Nir-Paz, Hadil Onallah, Michal Dekel, Yechiel N Gellman, Amir Haze, Ronen Ben-Ami, Ron Braunstein, Ronen Hazan, Danna Dror, Yonatan Oster, Meir Cherniak, Fabienne Attal, Ana Raquel Barbosa, Helena Dordio, Alexandra Wagner, Daniela Jones-Dias, José Neves, Margarida Barreto, Clara Leandro, Sofia Côrte-Real, Miguel Garcia

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引用次数: 0

Abstract

Background: Phage therapy offers a promising alternative for treating serious infections, including diabetic foot ulcers (DFUs), through the lytic action of phages. This randomized double-blind study was conducted to evaluate the safety and tolerability of the TP-102 bacteriophage cocktail in patients with DFUs non-infected and infected with Staphylococcus aureus, Pseudomonas aeruginosa, and/or Acinetobacter baumannii.

Methods: Nineteen participants with DFUs were randomized after susceptibility testing. TP-102 was applied topically at 10⁹ plaque-forming units (PFUs)/mL/cm³ to the target ulcer: 1 week for non-infected DFUs and 28 days for infected DFUs (PEDIS grade 2/3). The study was conducted in Israel.

Findings: Main outcomes included the incidence and severity of TP-102-related adverse events, microbiological data, and ulcer healing. Thirteen patients received TP-102. No treatment-related adverse events were reported. Although the study was underpowered to determine the superiority of TP-102 over placebo, a greater proportion of patients in the TP-102 + standard of care (SOC) group showed microbiological reduction of target bacteria (t = 26) compared to the placebo + SOC group (80% versus 50%, p = 1.000). Additionally, a higher proportion of TP-102 patients reached 50% and 75% wound closure compared to placebo (5/7 [71.4%] versus 1/3 [33.3%], p = 0.500 and 2/7 [28.6%] versus none, p = 1.000, respectively). One patient in the TP-102 group achieved wound closure.

Conclusions: TP-102 was well tolerated and safe, showing potential as a groundbreaking treatment in this field. Further studies are needed to confirm its safety and efficacy in larger populations with diabetic foot infections (ClinicalTrials.gov: NCT04803708).

Funding: None to declare.

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TP-102噬菌体鸡尾酒在感染和非感染糖尿病足溃疡患者中的安全性和耐受性的随机双盲研究

背景：噬菌体疗法通过噬菌体的裂解作用，为治疗严重感染，包括糖尿病足溃疡（DFUs）提供了一种有希望的替代方法。这项随机双盲研究旨在评估TP-102噬菌体鸡尾酒在未感染和感染金黄色葡萄球菌、铜绿假单胞菌和/或鲍曼不动杆菌的DFUs患者中的安全性和耐受性。方法：对19例DFUs患者进行药敏试验后随机选取。TP-102以10⁹斑块形成单位(pfu)/mL/cm³局部应用于目标溃疡：未感染dfu 1周，感染dfu 28天（PEDIS 2/3级）。这项研究在以色列进行。研究结果：主要结局包括tp -102相关不良事件的发生率和严重程度、微生物学数据和溃疡愈合。13例患者接受TP-102治疗。未见治疗相关不良事件的报道。虽然该研究不足以确定TP-102优于安慰剂，但与安慰剂+ SOC组相比，TP-102 +标准护理（SOC）组中更大比例的患者显示目标细菌的微生物减少（t = 26）（80%对50%，p = 1.000）。此外，与安慰剂相比，TP-102患者创面愈合达到50%和75%的比例更高（5/7[71.4%]对1/3 [33.3%],p = 0.500; 2/7[28.6%]对无创面愈合，p = 1.000）。TP-102组1例患者创面愈合。结论：TP-102具有良好的耐受性和安全性，有望成为该领域的突破性治疗药物。需要进一步的研究来证实其在糖尿病足感染人群中的安全性和有效性（ClinicalTrials.gov: NCT04803708）。资金：没有公布。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

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