GMEB-SASS: A Gene-Modified Skin Substitute for RDEB Treatment

Официальное название

Genetically Modified Epidermolysis Bullosa Self-Assembled Skin Substitute (GMEB-SASS) to Treat Patients Suffering From Recessive Dystrophic Epidermolysis Bullosa (RDEB)

Обзор

This study is being done to find out if a new type of skin graft, called GMEB-SASS, is safe and effective for helping wounds heal in people with RDEB (Recessive Dystrophic Epidermolysis Bullosa). The GMEB-SASS graft contains two types of living skin cells: keratinocytes and fibroblasts. It is made in a laboratory using a small sample of the patient's own skin. To help the patient's skin cells produce a missing protein called type VII collagen, scientists grow the patient's cells in the lab and use a virus-like tool (called a retroviral vector) to give the cells the correct instructions. This allows the cells to make the normal protein that is missing in people with RDEB. The graft is designed to be permanent, and the goal is to improve wound healing by replacing damaged skin cells with healthy ones.

Подробное описание

The GMEB-SASS is a skin tissue composed of living cells genetically modified in the laboratory to express a functional form of type VII collagen. The GMEB-SASS integrates with the patient's skin once grafted. The graft is autologous and expected to be permanent.

This is a first-in-human trial aiming to explore indications of the safety and efficacy of the GMEB-SASS skin graft in healing skin wounds in RDEB patients. Adults and children are included. However, a risk mitigation measure was added in order that at least some safety data from adults be available before the pediatric population is treated. Therefore, the study design is adaptative and divided into two phases: a learning phase (phase A) and a confirmatory phase (phase B).

In the present trial, the investigators hypothesize that retroviral transfer of the COL7A1 gene, combined with the use of the self-inactivated (SIN) COL7A1 vector, will restore a functional dermo-epidermal junction in the bilayer tissue-engineered skin produced at the LOEX research center by the self-assembly method. The method for the production of substitutes is similar to the one used in the ongoing clinical trial for the treatment of burn patients (ClinicalTrials.gov Identifier: NCT02350205) using SASS, with the exception of gene modification.

An important issue in RDEB patients is that their skin is colonized by bacteria due to the continuous presence of wounds. The method used to decontaminate the graft bed is crucial to ensure proper integration of the GMEB-SASS. The proposed intervention in this trial involves two surgical steps: the use of allografts to prepare the graft bed in a first step, followed by the application of the GMEB-SASS a few days later. This approach will be applied to at least participants enrolled in Phase A of the study.

The maximum daily dose per grafting session is the number of GMEB-SASS covering a maximum of 9% of the total body surface area. The number will be calculated based on the participant's height, weight, and age.

Вмешательства

• Препарат Genetically Modified Epidermolysis Bullosa Self-Assembled Skin Substitute (GMEB-SASS)
  Wound debridement will be performed, followed by the application of temporary allogeneic skin grafts for 3-5 days. The allografts will then be removed, and the GMEB-SASS grafts will be applied.

Первичные конечные точки

• Adverse events [Срок оценки: Up to 12 months]
• Pain score changes using a Visual Analogue Scale (VAS) [Срок оценки: Baseline, week 2, months 1, 3, 6 and 12]
• Itch score changes using a Visual Analogue Scale (VAS) [Срок оценки: Baseline, week 2, months 1, 3, 6 and 12 post intervention]

Вторичные конечные точки (3)

• Percentage of the grafted GMEB-SASS surface area that has healed [Срок оценки: Week 2, months 1, 3, 6 and 12 post intervention]
• iscorEB questionnaire - clinician portion [Срок оценки: Baseline, months 3 and 12 post intervention]
• Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) [Срок оценки: Time Frame: Baseline, months 3 and 12 post intervention]

Критерии участия

Критерии включения

• Age

Learning phase:

• Subjects 1 to 3: Eighteen (18) years old or older.
• Subjects 4 to 6: Twelve (12) years old or older.
• Subjects 7 to 9: Seven (7) years old or older.

Other Inclusion Criteria:

• Clinical diagnosis of recessive dystrophic epidermolysis bullosa (RDEB) with confirmed biallelic pathogenic variant in the COL7A1 gene.
• Candidates - or their parents/caregivers if the candidates have limited comprehension, who are able to understand the study and to comply with the study procedures.
• On the day of grafting, one or more blistered and/or erosive skin areas on the trunk and/or extremities large enough to graft at least three 25 to 50 cm2 GMEB-SASS grafts.
• Ability to undergo anesthesia.

Критерии исключения

• Medical instability limiting the ability to travel to the investigative center.
• Any medical condition or illness that may impact study participation or compromise the safety of the participants, as per the investigator's judgment.
• Evidence of systemic infection.
• Current evidence or a history of non-metastatic or metastatic squamous cell carcinoma at the site to be grafted.
• Any clinically significant abnormal laboratory values or abnormal findings identified during physical examination or through medical history that could compromise participant safety, as per the investigator's judgment.
• History of or known allergy to bovine proteins.
• Active drug or alcohol addiction.
• Female candidate who are pregnant or breast-feeding.
• Candidate who has received immunotherapy, including oral corticosteroids (Prednisolone > 1 mg/kg), for more than one week, within 2 weeks prior to the study intervention (initial biopsy and GMEB-SASS grafting) (intranasal and topical preparations are permitted).
• Candidate who has received chemotherapy within 60 days prior to the study intervention (initial biopsy and GMEB-SASS grafting).
• Candidate who has received, in the last 6 months prior to the study intervention (initial biopsy and GMEB-SASS grafting), any gene therapy, chemical or biological product modifying collagen 7 expression.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• The Hospital for Sick Children (SickKids) — Toronto

Идентификаторы

NCT: NCT07193134 · LOEX 020 · 291541

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗