Efficacy, Safety, and Tolerability of Topical TCP-25 Gel in Epidermolysis Bullosa: A Randomized, Double-Blind, Vehicle-Controlled Phase 2 Study

The primary objective of this study is to evaluate the **efficacy** of TCP-25 gel in promoting wound healing and improving symptoms in patients with Dystrophic Epidermolysis Bullosa (DEB) or Junctional Epidermolysis Bullosa (JEB). This is clinically relevant as these conditions are characterized by fragile skin and chronic wounds, and effective treatments are limited. Additionally, the study aims to assess the **safety** and **tolerability**, including local tolerability, of TCP-25 gel in these patients, which is crucial for ensuring that the treatment is not only effective but also safe for long-term use.

Secondary objectives include evaluating the systemic exposure to TCP-25 in patients with DEB or JEB. Understanding systemic exposure is important to determine the potential for systemic side effects and to ensure that the treatment remains localized to the target area.

The clinical trial focuses on evaluating the efficacy and safety of TCP-25 gel in patients diagnosed with **Epidermolysis Bullosa** (EB), specifically targeting those with Dystrophic Epidermolysis Bullosa (DEB) or Junctional Epidermolysis Bullosa (JEB). The study population includes both male and female participants, with an age range starting from 4 years old. Initially, the trial will enroll patients aged 12 years and older, with the inclusion of younger pediatric patients aged 4 to 11 years contingent upon a positive safety review. Participants must have a documented diagnosis of DEB or JEB, confirmed through genetic testing or skin biopsy with immunofluorescence mapping. The trial population is selected based on the presence of at least one well-matched index wound pair or a large continuous wound suitable for study purposes. The sponsor has not provided information regarding the total number of participants. The study includes a vulnerable population, emphasizing the need for careful monitoring and ethical considerations throughout the trial.

The clinical trial is designed as a **randomized**, **double-blind**, vehicle-controlled Phase 2 study to evaluate the efficacy, safety, and tolerability of topically applied TCP-25 in patients with **epidermolysis bullosa**. The trial aims to assess the efficacy of TCP-25 gel in promoting wound healing and improving symptoms in patients with dystrophic epidermolysis bullosa (DEB) or junctional epidermolysis bullosa (JEB). The study will also evaluate the safety and local tolerability of the gel. The trial is expected to commence recruitment on December 1, 2024, and conclude by December 1, 2026.

Participants will be involved in the study for a maximum treatment period of one month. The study will include an initial screening visit to confirm eligibility, which requires a documented diagnosis of DEB or JEB confirmed by genetic testing or skin biopsy. Participants must be at least 4 years old, with initial enrollment focusing on those aged 12 years and older. The inclusion of younger participants will be contingent upon a positive safety review by a Data Monitoring Committee (DMC) after at least three adolescents have completed four weeks of treatment.

Following the screening, participants will be randomly assigned to receive either the TCP-25 gel or a placebo, which is a sterile agent for cutaneous application identical to the TCP-25 gel but without the active pharmaceutical ingredient. The primary endpoint is the efficacy of TCP-25 gel compared to the placebo in reducing the open index wound area by Day 56 relative to baseline. Secondary endpoints include changes in procedural pain, clinical impression of the treatment area, TCP-25 plasma concentrations, and the frequency and seriousness of adverse events.

Study visits will be scheduled to monitor the participants' progress, assess the primary and secondary endpoints, and ensure safety and tolerability. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted. Participants may be withdrawn from the study early if they experience significant adverse events or if they do not adhere to the study protocol. The trial is not classified as a low-intervention study and is conducted in accordance with regulatory standards.

The clinical trial involves the evaluation of **TCP-25**, a gel formulation designed for **topical application on wounds**. The active pharmaceutical ingredient in TCP-25 is a peptide sequence: H-GLY-LYS-TYR-GLY-PHE-TYR-THR-HIS-VAL-PHE-ARG-LEU-LYS-LYS-TRP-ILE-GLN-LYS-VAL-ILE-ASP-GLN-PHE-GLY-GLU-OH. This peptide is classified as a protein of other origin. The gel is intended for use in patients with **Epidermolysis Bullosa** (EB), specifically targeting wound healing and symptom improvement in **Dystrophic Epidermolysis Bullosa** (DEB) or **Junctional Epidermolysis Bullosa** (JEB). The pharmaceutical form of TCP-25 is a gel, and it is applied topically on the wound. The trial will assess the efficacy, safety, and tolerability of TCP-25, with a focus on local tolerability. The maximum treatment period is set at one day, with no specified maximum daily or total dose amount.

The study also includes a **placebo** control, which is a sterile agent for cutaneous application. This placebo is identical in composition to the TCP-25 gel, except it does not contain the active pharmaceutical ingredient. The placebo is used to provide a vehicle-controlled comparison to evaluate the true efficacy of the TCP-25 gel. The placebo is also applied topically on the wound, mirroring the administration route of the experimental treatment. The use of a placebo allows for a double-blind study design, ensuring that neither the participants nor the investigators are aware of which treatment is being administered, thereby reducing bias in the assessment of outcomes.

The efficacy of the TCP-25 gel in the clinical trial will be assessed primarily by evaluating the reduction in the open index wound area until Day 56 relative to the baseline. This primary endpoint will provide a direct measure of the gel's effectiveness in promoting wound healing in patients with **Epidermolysis Bullosa**. Secondary endpoints will include changes in procedural pain, assessed using the Wong Baker FACES® Pain Rating Scale, and changes from baseline in the clinical impression of the overall treatment area using global impression scales. Additionally, TCP-25 plasma concentrations will be measured, and the frequency, intensity, and seriousness of adverse events will be monitored. Local tolerability at the area of investigational medicinal product (IMP) application will also be evaluated, alongside clinically significant changes from baseline in vital signs, including systolic and diastolic blood pressure and pulse rate, as well as physical examination findings.