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Background <p>Despite the high morbidity and severe consequences of epidermolysis bullosa (EB), current treatments remain inadequate, lacking efficacy and the ability to target the microbial and inflammatory components of EB wounds. In this first-in-human open-label, single-arm study—part 3 of a 3-part Phase 1 clinical trial—we examined the safety, tolerability, and systemic exposure of topically applied TCP-25, a thrombin-derived C-terminal peptide with demonstrated anti-inflammatory, antimicrobial, and wound-healing properties in murine and porcine infection models.</p> Results <p>Five patients with inherited recessive dystrophic EB received TCP-25 gel, applied to a 50-cm<sup>2</sup> primary wound treatment area, which was compared with a reference wound treatment area which received standard wound care alone. TCP-25 gel was also applied to a 50-cm<sup>2</sup> secondary wound treatment area of a higher age or in a more complicated area. TCP-25 gel was administered at escalating doses of 7.25 mg, 14.5 mg, 21.5 mg, and 43.0 mg, 3 times per week over 4 consecutive 1-week treatment periods. For the primary safety endpoint, 11 adverse events were recorded, 10 unlikely related to treatment and mild or moderate in severity, with one possibly linked to gel adhesion. Additionally, no abnormal local reactions were observed in any wound treated with TCP-25, nor in any reference wound, compared to expected wound healing outcomes. For the secondary endpoint, we did not observe any systemic plasma uptake of TCP-25 in any participant. In an exploratory analysis, we observed a steady reduction in open wound size in TCP-25-treated primary wounds, culminating in a median reduction of 76% from baseline to Day 29. Reference wounds exhibited variable changes in wound size, including some increases in size at earlier time points. Secondary wounds that were treated with TCP-25 also decreased steadily, reaching a median open wound size reduction of 78% on day 29. Additionally, TCP-25 demonstrated potential efficacy in accelerating wound healing.</p> Conclusions <p>Topical TCP-25 gel was safe and well tolerated and showed no systemic uptake in patients with dystrophic EB, demonstrating promising effects on wound healing.</p> Trial Registration <p>Clinical trial NCT05378997 was registered 2022–05-12 (<a href="https://clinicaltrials.gov/study/NCT05378997">https://clinicaltrials.gov/study/NCT05378997</a>) and amended 2024–02-12 to include Part-3 on dystrophic EB. The amendment was prospectively registered at EudraCT (2021-004728-14).</p>

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Results of a non-randomized, open-label phase I study evaluating the novel immunomodulatory peptide TCP-25 for treatment of dystrophic epidermolysis bullosa

  • 期刊论文

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  • 发表日期：

    2025年12月2日

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  • Karl Wallblom,
  • Katja Holmgren,
  • Sigrid Lundgren,
  • Emma Belfrage,
  • Torborg Hoppe,
  • Matilda Hugerth,
  • Anna-Karin Lindqvist,
  • Enikö Sonkoly,
  • Artur Schmidtchen

摘要

Background

Despite the high morbidity and severe consequences of epidermolysis bullosa (EB), current treatments remain inadequate, lacking efficacy and the ability to target the microbial and inflammatory components of EB wounds. In this first-in-human open-label, single-arm study—part 3 of a 3-part Phase 1 clinical trial—we examined the safety, tolerability, and systemic exposure of topically applied TCP-25, a thrombin-derived C-terminal peptide with demonstrated anti-inflammatory, antimicrobial, and wound-healing properties in murine and porcine infection models.

Results

Five patients with inherited recessive dystrophic EB received TCP-25 gel, applied to a 50-cm2 primary wound treatment area, which was compared with a reference wound treatment area which received standard wound care alone. TCP-25 gel was also applied to a 50-cm2 secondary wound treatment area of a higher age or in a more complicated area. TCP-25 gel was administered at escalating doses of 7.25 mg, 14.5 mg, 21.5 mg, and 43.0 mg, 3 times per week over 4 consecutive 1-week treatment periods. For the primary safety endpoint, 11 adverse events were recorded, 10 unlikely related to treatment and mild or moderate in severity, with one possibly linked to gel adhesion. Additionally, no abnormal local reactions were observed in any wound treated with TCP-25, nor in any reference wound, compared to expected wound healing outcomes. For the secondary endpoint, we did not observe any systemic plasma uptake of TCP-25 in any participant. In an exploratory analysis, we observed a steady reduction in open wound size in TCP-25-treated primary wounds, culminating in a median reduction of 76% from baseline to Day 29. Reference wounds exhibited variable changes in wound size, including some increases in size at earlier time points. Secondary wounds that were treated with TCP-25 also decreased steadily, reaching a median open wound size reduction of 78% on day 29. Additionally, TCP-25 demonstrated potential efficacy in accelerating wound healing.

Conclusions

Topical TCP-25 gel was safe and well tolerated and showed no systemic uptake in patients with dystrophic EB, demonstrating promising effects on wound healing.

Trial Registration

Clinical trial NCT05378997 was registered 2022–05-12 (https://clinicaltrials.gov/study/NCT05378997) and amended 2024–02-12 to include Part-3 on dystrophic EB. The amendment was prospectively registered at EudraCT (2021-004728-14).