Study on Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa Using Skin Grafts with Genetically Corrected Autologous Keratinocytes and Fibroblasts

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What is this study about?

This clinical trial is focused on a rare genetic skin condition called Recessive Dystrophic Epidermolysis Bullosa (RDEB). This condition causes the skin to be very fragile, leading to blisters and wounds from minor injuries. The study is testing a new treatment that involves using a special type of skin graft. This graft is made from the patient’s own skin cells, which are genetically modified to correct a specific gene known as COL7A1. This gene is responsible for producing a protein called type VII collagen, which helps hold the layers of skin together.

The purpose of the study is to evaluate the safety of this new treatment. Participants will receive the genetically corrected skin graft, and their health will be monitored over time. The study will follow participants for a total of five years, with regular check-ups at various intervals to ensure the treatment is safe and to observe any changes in the skin. These check-ups will include skin examinations and other assessments to track the progress of the grafted skin and overall health.

Throughout the study, researchers will look for any side effects or reactions to the treatment. They will also assess how well the grafted skin is healing and whether it improves the condition of the skin. This trial aims to provide valuable information on whether this innovative approach can offer a new option for managing RDEB and improving the quality of life for those affected by this challenging condition.

1 initial assessment

The trial begins with an initial assessment to confirm eligibility. This includes a clinical and molecular diagnosis of recessive dystrophic epidermolysis bullosa (RDEB) with confirmed mutations in the COL7A1 gene.

A skin biopsy is performed to check for reduced staining of C7 protein and the presence of abnormal anchoring fibrils. The biopsy also checks for the presence of the non-collagenous-1 domain of C7.

2 grafting procedure

Eligible participants undergo a grafting procedure using a skin equivalent graft that has been genetically corrected with a COL7A1-encoding SIN retroviral vector.

The procedure requires the ability to undergo anesthesia.

3 post-grafting follow-up

After the grafting, follow-up visits are scheduled at 1 month (M1), 2 months (M2), 3 months (M3), 6 months (M6), and 12 months (M12) to evaluate the safety of the graft.

The follow-up includes monitoring for any adverse events or reactions.

4 long-term follow-up

Long-term follow-up continues at 18 months (M18), 24 months (M24), 30 months (M30), 36 months (M36), 42 months (M42), 48 months (M48), 54 months (M54), and 60 months (M60).

This includes skin biopsy analysis to assess C7 protein expression and the morphology of anchoring fibrils, as well as serum analysis for anti-C7 antibodies and T-cell responses.

5 clinical assessments

Clinical assessments are conducted at each follow-up visit to evaluate scar quality, changes in blister numbers, and the clinical appearance of the grafted skin.

Additional assessments include measuring changes in itchiness and quality of life.

Who Can Join the Study?

Must be 18 years old or older.
Must have a clinical and molecular diagnosis of Recessive Dystrophic Epidermolysis Bullosa (RDEB), which means the condition is confirmed by specific tests showing changes in both copies of the COL7A1 gene.
Must have significantly reduced staining of a protein called C7 in a skin sample, checked using a special technique called immunofluorescence microscopy (IF).
Must have a reduced number or abnormal shape of structures called anchoring fibrils, confirmed by a detailed examination method known as TEM.
Must show the presence of a specific part of the C7 protein called the non-collagenous-1 domain (NC-1) in a skin sample, checked by immunofluorescence microscopy (IF) and/or a test called Western blot analysis.
Must have at least 100 square centimeters of skin that is blistered or has open sores, including long-lasting wounds, that are suitable for a skin graft.
Must be able to undergo anesthesia, which is a way to make you sleep or not feel pain during the skin grafting procedure.
Must be willing and able to provide informed consent, meaning you agree to participate in the study after understanding all the details and risks.

Who Cannot Join the Study?

Patients who do not have Recessive dystrophic epidermolysis bullosa (RDEB) cannot participate. This is a specific skin condition.
Individuals who are not within the specified age range for the study cannot participate. The study is open to certain age groups only.
Both male and female participants are eligible, but those who do not meet other criteria cannot participate.
Participants who are considered part of a vulnerable population are not eligible. This means people who might need special protection or care.

Where you can join this trial?

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Site Name	City	Country	Status
Imivvxi Idaykaexc Fmv Gflhbua Dudyuam Haixbhw Nlrxbw	Paris	France

Trial status

Country	Status	Recruitment Start
France	Recruiting	10.01.2020

Trial locations

Investigated drugs:

AUTOLOGOUS KERATINOCYTES AND FIBROBLASTS TRANSDUCED WITH A RETROVIRAL VECTOR ENCODING COL7A1 CDNA

Autologous Skin Equivalent Grafts are used in this trial. These are skin grafts made from the patient’s own skin cells. The cells are taken from the patient, grown in a lab, and then used to create a skin graft that can be placed back onto the patient’s body. This helps to reduce the risk of rejection since the graft is made from the patient’s own cells.

SIN Retroviral Vector Encoding COL7A1 is a type of gene therapy used in this trial. It involves using a specially designed virus to deliver a healthy copy of the COL7A1 gene into the patient’s skin cells. This gene is important for producing a protein that helps hold the layers of skin together. By correcting the gene, the therapy aims to improve the skin’s strength and function in patients with RDEB, a condition that causes fragile skin.

Investigated diseases:

Epidermolysis bullosa

Recessive Dystrophic Epidermolysis Bullosa (RDEB) – This is a rare genetic skin disorder characterized by fragile skin that easily blisters and tears from minor friction or trauma. It is caused by mutations in the COL7A1 gene, which affects the production of a protein called collagen VII, essential for anchoring the layers of skin together. Individuals with RDEB often experience chronic wounds, scarring, and may have involvement of other body areas such as the mouth and esophagus. The condition is present from birth and can lead to significant skin damage over time. Blisters and wounds can become infected, and the skin may heal with scarring, leading to further complications. The severity of symptoms can vary widely among affected individuals.

Trial ID:

2024-518368-10-00

Protocol code:

C12-48

NCT ID:

NCT04186650

Trial Phase:

Phase I and Phase II (Integrated) – First administration to humans

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Study on Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa Using Skin Grafts with Genetically Corrected Autologous Keratinocytes and Fibroblasts

What is this study about?

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