A Phase 1/2A Single Center Trial of Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Using the Drug LZRSE-Col7A1 Engineered Autologous Epidermal Sheets (LEAES)

SU-10202010-7130

This trial will create a skin graft, which the investigators call "LEAES," using the patient's own skin cells that have been genetically engineered in the lab to express a missing protein called type VII collagen. The corrected cells will be transplanted back to the patient.

2010-10-05

2022-03-09

2022-03-09

Completed

Early phase I

12

Inclusion Criteria: 1. Clinical diagnosis of recessive dystrophic epidermolysis bullosa (RDEB) 2. 13 years old or older and willing and able to give assent/consent 3. Confirmation of RDEB diagnosis by immunofluorescence (IF) and electron microscopy (EM) 4. NC1\[+\] and mAb LH24 antibody staining negative 5. RDEB type VII collagen mutations in subject and carrier parents confirmed 6. At least 100 to 200 cm2 areas of open erosions on the trunk and/or extremities suitable for skin grafting 7. Able to undergo adequate anesthesia to allow grafting procedures to take place. Exclusion Criteria: 1. Medical instability limiting ability to travel to Stanford University Medical Center 2. The presence of medical illness expected to complicate participation and/or compromise the safety of this technique, such as active infection with HIV, hepatitis B or hepatitis C, as determined by hepatitis B surface antigen screening, detection of hepatitis C antibodies, or positive result of hepatitis C polymerase chain reaction (PCR) analysis. 3. Antibodies to type VII collagen associated antigens 4. Active infection in the area that will undergo grafting 5. Evidence of systemic infection 6. Current evidence or a history of squamous cell carcinoma in the area that will undergo grafting 7. Active drug or alcohol addiction 8. Hypersensitivity to vancomycin or amikacin 9. Receipt of chemical or biological study product for the specific treatment of RDEB in the past six months 10. Positive pregnancy test or breast-feeding 11. Clinically significant abnormalities (Grade 2 or higher on the National Cancer Institute \[NCI\] toxicity scale) on laboratory tests performed prior to grafting, except for the following specific exclusionary laboratory threshold results, subject to approval or exemption by the EB physician: * Albumin \< 2.5 g/dL * Leukocytes \> 20K/uL * Hemoglobin \< 7.5 g/dL. Low hemoglobin will be treated at the discretion of the investigators and the EB physician. * Additional exceptions may be made at the discretion of the investigators and the EB physician. 12. Clinically significant abnormalities (Grade 2 or higher on the NCI toxicity scale) identified through medical history and physical examination on Day 0, with the following exceptions: * Anorexia, can enroll up to Grade 4 (inclusive) * Constipation, can enroll up to Grade 2 (inclusive) * Dysphagia, can enroll up to Grade 4 (inclusive) * Keratitis, can enroll up to Grade 4 (inclusive) * Bone pain, can enroll up to Grade 2 (inclusive) * Additional exceptions may be made at the discretion of the investigators and the EB physician.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 12, 'type': 'ACTUAL'}}

2023-08-22