TCP-25 gel may accelerate wound healing in RDEB: Phase 1 trial
Drug candidate was also not absorbed into bloodstream
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TCP-25 gel is well-tolerated by individuals with recessive dystrophic epidermolysis bullosa (RDEB) and may effectively accelerate wound healing, according to a Phase 1 trial.
The Phase 1 trial (NCT05378997) compared TCP-25 administered in conjunction with standard care to standard care alone over four weeks. The trial also demonstrated that the treatment, applied as a gel directly to wounds, was not absorbed into the bloodstream.
According to researchers, “topical TCP-25 gel was safe and well tolerated … demonstrating promising effects on wound healing.”
The study, “Results of a non-randomized, open-label phase I study evaluating the novel Immunomodulatory peptide TCP-25 for treatment of dystrophic epidermolysis bullosa,” was published in the Orphanet Journal of Rare Diseases.
TCP-25 designed to speed up wound healing
DEB is a form of epidermolysis bullosa, a group of rare diseases that cause the skin to be extremely fragile, easily tearing and blistering. It is caused by mutations in the COL7A1 gene, which codes for part of the type VII collagen protein that connects the different layers of the skin.
TCP-25 is an engineered peptide, or short chain of amino acids, developed by Xinnate and designed to accelerate wound healing and promote tissue repair by reducing inflammation and neutralizing disease-driving bacteria. TCP-25 is based on 25 amino acids of thrombin, a protein involved in clotting, and is formulated in a proprietary hydrogel for local wound application. Amino acids are the building blocks of proteins.
In this study, researchers in Sweden, including two scientists at Xinnate, presented data from part 3 of a Phase 1 trial that assessed the safety and preliminary efficacy of multiple administrations of four dose levels of TCP-25 (7.25 mg, 14.5 mg, 21.5 mg, and 43 mg), three times per week over four consecutive weeks, in five people with DEB. Participants were recruited at two university hospitals in Sweden.
Three wound treatment areas were defined for each patient, including a primary wound not located in a body region with a high likelihood of accidental trauma, such as the knee or an elbow, matched to a reference wound treated with standard care only. A secondary wound, in a body region with a high chance of trauma or within the higher allowed wound age of less than nine months, was also treated.
Two primary wounds closed completely within a month
Participants had a median age of 18 years, and all were males. All were diagnosed at an early age with recessive DEB. Their wounds were generally located on the legs, hips, or upper arm. Before treatment, the median area of primary wounds was 5 square centimeters (cm2). The area of reference and secondary wounds was 2.4 cm2 and 17 cm2, respectively.
Of the 11 adverse events reported overall, only one, a product adhesion issue, was deemed possibly related to the gel treatment. All events were mild to moderate in severity, including the common cold in three patients and wound complications in two patients.
There were no abnormal local reactions, such as swelling, redness, or scaling, in any wound area compared with expected wound outcomes.
Additionally, there was no measurable uptake of TCP-25 in the bloodstream, measured about 1.5 hours after the last treatment administration on day 22.
We noted a possible positive treatment effect of TCP-25 on wound healing speed and open wound area reduction.
Primary wounds decreased over time upon TCP-25 application. After eight days, three of five wounds had closed by at least 50%. After almost a month, two primary wounds had completely closed, and the others decreased by at least 50%. Overall, the size of open wounds was reduced by a median of 3.9 cm2, corresponding to a 76% reduction, after 29 days.
Similar results were seen for secondary wounds, which were reduced by 78% after 29 days of TCP-25 treatment. Secondary wounds, the team noted, were larger and more complex due to their location and how long-standing they were.
Reference wounds did not decrease during the study. Three wounds became larger after eight days, two of which remained larger than at the study start until at least day 22. By day 29, wounds were reduced by a median of 67%, and only one had closed completely.
“We noted a possible positive treatment effect of TCP-25 on wound healing speed and open wound area reduction,” the investigators concluded. “To this end, a larger study that is powered for detecting efficacy about wound healing parameters is planned and will further examine this promising new concept for wound healing.”
The Phase 2 STEP-study trial (NCT06594393) is designed to evaluate the efficacy of TCP-25 in up to 26 patients, ages 4 and older, with DEB or junctional epidermolysis bullosa. The trial will enroll patients at a hospital in Sweden who will receive TCP-25 or a placebo.
