# A First‐In‐Human Randomized Controlled Phase 1 Study Assessing the Safety and Tolerability of Topical TCP‐25 Gel in Epidermal Suction Blister Wounds

## TL;DR

A first-in-human study found that a new topical gel, TCP-25, is safe and well-tolerated for treating wounds without entering the bloodstream.

## Contribution

This is the first clinical trial to evaluate the safety and pharmacokinetics of TCP-25 in humans with epidermal wounds.

## Key findings

- TCP-25 gel was safe and well tolerated in healthy volunteers with no serious adverse events.
- TCP-25 showed no measurable systemic exposure in plasma samples.
- Exploratory results suggested reduced wound exudation with TCP-25 treatment.

## Abstract

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.

What is the current knowledge on the topic?
○In preclinical models of wound infection, the immunomodulatory peptide TCP‐25 has consistently demonstrated dual anti‐inflammatory and antimicrobial activities that facilitate wound healing, underscoring its therapeutic potential.○TCP‐25 is being developed as a topical treatment for epidermolysis bullosa (EB) wounds.○However, at the time of this study, no safety, tolerability, or pharmacokinetic data in humans had been reported.
What question did this study address?
○This first‐in‐human study aimed to examine the safety, tolerability, and pharmacokinetics of TCP‐25 gel in healthy volunteers with suction blister‐induced wounds.
What does this study add to our knowledge?
○Topical application of TCP‐25 gel was safe and well tolerated in human volunteers with epidermal wounds, consistent with previous preclinical animal studies.○No systemic exposure to TCP‐25 was detected, and no new safety concerns were observed.○Exploratory analyses indicated that TCP‐25 reduced wound exudation.
How might this change clinical pharmacology or translational science?
○Based on its safety and tolerability profile, these findings support the further clinical development of TCP‐25 in wound treatment.○Pending evaluation in patients with disease‐related wounds that are more complex and difficult to treat, TCP‐25 may represent a novel treatment modality based on its multifaceted action on inflammation and bacteria.

What is the current knowledge on the topic?
○In preclinical models of wound infection, the immunomodulatory peptide TCP‐25 has consistently demonstrated dual anti‐inflammatory and antimicrobial activities that facilitate wound healing, underscoring its therapeutic potential.○TCP‐25 is being developed as a topical treatment for epidermolysis bullosa (EB) wounds.○However, at the time of this study, no safety, tolerability, or pharmacokinetic data in humans had been reported.

In preclinical models of wound infection, the immunomodulatory peptide TCP‐25 has consistently demonstrated dual anti‐inflammatory and antimicrobial activities that facilitate wound healing, underscoring its therapeutic potential.

TCP‐25 is being developed as a topical treatment for epidermolysis bullosa (EB) wounds.

However, at the time of this study, no safety, tolerability, or pharmacokinetic data in humans had been reported.

What question did this study address?
○This first‐in‐human study aimed to examine the safety, tolerability, and pharmacokinetics of TCP‐25 gel in healthy volunteers with suction blister‐induced wounds.

This first‐in‐human study aimed to examine the safety, tolerability, and pharmacokinetics of TCP‐25 gel in healthy volunteers with suction blister‐induced wounds.

What does this study add to our knowledge?
○Topical application of TCP‐25 gel was safe and well tolerated in human volunteers with epidermal wounds, consistent with previous preclinical animal studies.○No systemic exposure to TCP‐25 was detected, and no new safety concerns were observed.○Exploratory analyses indicated that TCP‐25 reduced wound exudation.

Topical application of TCP‐25 gel was safe and well tolerated in human volunteers with epidermal wounds, consistent with previous preclinical animal studies.

No systemic exposure to TCP‐25 was detected, and no new safety concerns were observed.

Exploratory analyses indicated that TCP‐25 reduced wound exudation.

How might this change clinical pharmacology or translational science?
○Based on its safety and tolerability profile, these findings support the further clinical development of TCP‐25 in wound treatment.○Pending evaluation in patients with disease‐related wounds that are more complex and difficult to treat, TCP‐25 may represent a novel treatment modality based on its multifaceted action on inflammation and bacteria.

Based on its safety and tolerability profile, these findings support the further clinical development of TCP‐25 in wound treatment.

Pending evaluation in patients with disease‐related wounds that are more complex and difficult to treat, TCP‐25 may represent a novel treatment modality based on its multifaceted action on inflammation and bacteria.