A First-In-Human Randomized Controlled Phase 1 Study Assessing the Safety and Tolerability of Topical TCP-25 Gel in...

Inflammation and infection remain unmet challenges in wounds of various etiologies, delaying healing, impacting quality of life, and increasing healthcare costs. The thrombin-derived C-terminal peptide TCP-25 has demonstrated dual anti-inflammatory and antibacterial activities in animal wound infection models, thereby promoting healing, highlighting its therapeutic potential as a wound treatment. This first-in-human, double-blind, randomized, within-person and placebo-controlled clinical trial (NCT05378997) evaluated the safety, tolerability, and pharmacokinetics of topical TCP-25 in healthy volunteers. Twenty-four participants each received four suction blister wounds (two per thigh), with two wounds treated with TCP-25 (either 0.86, 2.9, or 8.6 mg/mL) and two with placebo gel, 5 times over 8 days. For the primary safety endpoint, no serious or significant adverse events or withdrawals due to adverse events were reported. Twenty-one participants (88%) reported at least 1 adverse event; all were mild or moderate and judged to be unlikely related to TCP-25 treatment. No abnormal local reactions occurred and no clinically relevant changes in electrocardiogram, vital signs, laboratory parameters, or physical examination findings were observed between baseline and end of treatment. For the secondary endpoint, TCP-25 was undetectable (< 90 nmol/L) in all plasma samples at all timepoints. Thus, topical TCP-25 gel was safe and well tolerated by healthy volunteers with epidermal wounds, with no evidence of measurable systemic exposure. Exploratory analyses indicated reduced wound exudation with TCP-25 treatment, particularly at 2.9 and 8.6 mg/mL. Taken together, these findings support further clinical evaluation of TCP-25 in relevant patient populations.