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

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.

Keywords: Translation to patients; bacteriophage; clinical trial; diabetes; diabetic foot ulcers; infection; phage.