A Randomized, Double-blind, Vehicle-controlled Phase 2 Study to Evaluate Efficacy, Safety, and Tolerability of Topically Applied TCP-25 in Patients with Epidermolysis Bullosa

This is a Phase 2, double-blind, randomized, vehicle-controlled study designed to evaluate efficacy, safety, and tolerability of topically applied TCP-25 gel in patients with confirmed DEB or JEB. The study will implement intrasubject randomization, ie, pairs of matching index wounds will be randomly assigned to be treated with a local application of either TCP 25 gel or vehicle gel.

开始日期2025-03-31

申办/合作机构

Xinnate AB

NCT05378997 / Completed临床1期

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study in Healthy Male and Female Volunteers to Investigate the Safety, Tolerability, and Pharmacokinetics of Ascending Topical Doses of TCP-25 Applied to Epidermal Suction Blister Wounds and in Patients With Non-Healing Leg Ulcers and Patients With Dystrophic Epidermolysis Bullosa

This is a three-part, Phase I, first-in-human study designed to evaluate the safety, tolerability, and potential systemic exposure of multiple topical doses of TCP-25. Part I includes healthy volunteers with acute epidermal wounds formed by the suction blister technique. Part II includes patients with non-healing leg ulcers and Part III patients with dystrophic epidermolysis bullosa (DEB).

开始日期2022-04-07

申办/合作机构

Xinnate AB

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100 项与 TCP-25 相关的临床结果

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100 项与 TCP-25 相关的转化医学

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100 项与 TCP-25 相关的专利（医药）

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项与 TCP-25 相关的文献（医药）

2023-12-01·Advanced Healthcare Materials

Bioactive Suture with Added Innate Defense Functionality for the Reduction of Bacterial Infection and Inflammation

Article

作者: Schmidtchen, Artur ; Klementieva, Oxana ; Hartman, Erik ; Malmsten, Martin ; Strömdahl, Ann‐Charlotte ; Wasserstrom, Sebastian ; Kjellström, Sven ; Bond, Peter J. ; Petruk, Ganna ; Petrlova, Jitka ; Puthia, Manoj ; Butrym, Marta ; Caselli, Lucrezia ; Andersson, Madelene Å ; Raina, Deepak Bushan ; Samsudin, Firdaus

AbstractSurgical site infections (SSI) are a clinical and economic burden. Suture‐associated SSI may develop when bacteria colonize the suture surface and form biofilms that are resistant to antibiotics. Thrombin‐derived C‐terminal peptide (TCP)‐25 is a host defense peptide with a unique dual mode of action that can target both bacteria and the excessive inflammation induced by bacterial products. The peptide demonstrates therapeutic potential in preclinical in vivo wound infection models. In this study, the authors set out to explore whether TCP‐25 can provide a new bioactive innate immune feature to hydrophilic polyglactin sutures (Vicryl). Using a combination of biochemical, biophysical, antibacterial, biofilm, and anti‐inflammatory assays in vitro, in silico molecular modeling studies, along with experimental infection and inflammation models in mice, a proof‐of‐concept that TCP‐25 can provide Vicryl sutures with a previously undisclosed host defense capacity, that enables targeting of bacteria, biofilms, and the accompanying inflammatory response, is shown.

2023-02-01·BMJ Open

Study protocol for a phase 1, randomised, double-blind, placebo-controlled study to investigate the safety, tolerability and pharmacokinetics of ascending topical doses of TCP-25 applied to epidermal suction blister wounds in healthy male and female volunteers

Article

作者: Saleh, Karim ; Schmidtchen, Artur ; Lundgren, Sigrid ; Erdmann, Susanne ; Wallblom, Karl ; Fisher, Jane

IntroductionTCP-25 gel is intended for use in treatment of wound infection and inflammation. Current local therapies for wounds have limited efficacy to prevent infections and there are no wound treatments available today that target the excessive inflammation that often hampers wound healing in both acute and chronic wounds. There is therefore a high medical need for new therapeutic alternatives.Methods and analysisA randomised, double-blinded, first-in-human study was designed to evaluate the safety, tolerability and potential systemic exposure of three increasing doses of the TCP-25 gel applied topically on suction blister wounds in healthy adults. The dose-escalation will be divided into three sequential dose groups with eight subjects in each group (24 patients in total). Within each dose group, the subjects will receive four wounds, with two wounds on each thigh. Each subject will receive TCP-25 on one wound per thigh and placebo on one wound per thigh in a randomised double-blinded manner, with a reverse reciprocal position on each respective thigh, to a total of five doses over 8 days. An internal safety review committee will monitor emerging safety and plasma concentration data over the course of the study and must give a favourable recommendation prior to initiating the next dose group, which will receive placebo gel or a higher concentration of TCP-25 in exactly the same manner described above.Ethics and disseminationThe study will be performed in accordance with ethical principles consistent with the Declaration of Helsinki, ICH/GCPE6 (R2), European Union Clinical Trials Directive and applicable local regulatory requirements.This study is approved by the Swedish Medical Products Agency and the Swedish ethics committee under the registration number 2022-00527-01. The results of this study will be disseminated via publication to a peer-reviewed journal at the discretion of the Sponsor.Trial registration numberNCT05378997.

2021-07-01·Acta Biomaterialia1区 · 工程技术

Peptide-coated polyurethane material reduces wound infection and inflammation

1区 · 工程技术

Article

作者: Strömdahl, Ann-Charlotte ; Puthia, Manoj ; Ignatowicz, Lech ; Petruk, Ganna ; Butrym, Marta ; Wasserstrom, Sebastian ; Schmidtchen, Artur

There is an urgent need for treatments that not only reduce bacterial infection that occurs during wounding but that also target the accompanying excessive inflammatory response. TCP-25, a thrombin-derived antibacterial peptide, scavenges toll-like receptor agonists such as endotoxins and lipoteichoic acid and prevents toll-like receptor-4 dimerization to reduce infection-related inflammation in vivo. Using a combination of biophysical, cellular, and microbiological assays followed by experimental studies in mouse and pig models, we show that TCP-25, when delivered from a polyurethane (PU) material, exerts anti-infective and anti-inflammatory effects in vitro and in vivo. Specifically, TCP-25 killed the common wound pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, in both in vitro and in vivo assays. Furthermore, after its release from the PU material, the peptide retained its capacity to induce its helical conformation upon endotoxin interaction, yielding reduced activation of NF-κB in THP-1 reporter cells, and diminished accumulation of inflammatory cells and subsequent release of IL-6 and TNF-α in subcutaneous implant models in vivo. Moreover, in a porcine partial thickness wound infection model, TCP-25 treated infection with S. aureus, and reduced the concomitant inflammatory response. Taken together, these findings demonstrate a combined antibacterial and anti-inflammatory effect of TCP-25 delivered from PU in vitro, and in mouse and porcine in vivo models of localized infection-inflammation. STATEMENT OF SIGNIFICANCE: Local wound infections may result in systemic complications and can be difficult to treat due to increasing antimicrobial resistance. Surgical site infections and biomaterial-related infections present a major challenge for hospitals. In recent years, various antimicrobial coatings have been developed for infection prevention and current concepts focus on various matrices with added anti-infective components, including various antibiotics and antiseptics. We have developed a dual action wound dressing concept where the host defense peptide TCP-25, when delivered from a PU material, targets both bacterial infection and the accompanying inflammation. TCP-25 PU showed efficacy in in vitro and experimental wound models in mouse and minipigs.

100 项与 TCP-25 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
大疱性表皮松解	临床2期	瑞典	Xinnate AB	2025-03-31
水疱	临床1期	瑞典	Xinnate AB	2022-04-07
营养不良性大疱性表皮松解	临床1期	瑞典	Xinnate AB	2022-04-07
下肢溃疡	临床1期	瑞典	Xinnate AB	2022-04-07
创伤和损伤	临床1期	瑞典	Xinnate AB	2022-04-07