Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
The research project involves gene transfer into keratinocytes, which are the majority of the cells in the outer layer of skin. In this gene transfer trial we plan to biopsy some skin tissue, grow the cells in a skin cell culture (sterile dishes with special fluid that allows cells to grow and multiply) and then infect the cells with a virus that we have genetically engineered to insert the correct type VII collagen gene. The cells should then make type VII collagen.
The process of inserting the correct type VII collagen gene into cells is called "gene transfer." The virus used is called a "retrovirus." The virus is made so that it only delivers the type VII collagen gene and it should not spread to other parts of the body. During the study we will check for growth of the virus.
After cells have received gene transfer, we will grow the cells in culture into a sheet of cells that look like a plastic film. We plan to graft the sheet to wounds. Grafting means we will take cells from the culture and stitch them to the patient's skin.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LEAES treatment LZRSE-Col7A1 Engineered Autologous Epidermal Sheets (LEAES) |
Biological: LZRSE-Col7A1 Engineered Autologous Epidermal Sheets
This trial will create a graft, which we call "LEAES", of the patient's own skin that has been genetically engineered in our lab to express this missing protein.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Percentage surface area of wound healing [3, 6 and 12 months post grafting]
Wound dimensions, including length, width, and area (in cm2), will be obtained using the Canfield system. Changes in dimensions between visits as well as changes in dimensions from baseline will be recorded. Dimensions of untreated wounded skin will be used for comparison
- Investigator's assessment of graft [3, 6 and 12 months post grafting]
The graft site will be clinically evaluated with a global score of: 1) 100% to 75% healed, 2) 74% to 50% healed, 3) 49% to 25% healed, 4) 25% to 1% healed, 5) complete graft loss, or 6) unable to determine.
Secondary Outcome Measures
- duration of type VII collagen production [12 weeks, 25 weeks, and 52 weeks post grafting]
Skin biopsies will be obtained to evaluate expression of type VII collagen, both NC1 and NC2 epitopes, using immuno-electron microscopy and immuno-fluorescent light microscopy
Other Outcome Measures
- presence of anchoring fibrils [day 14, 4 weeks, 12 weeks, 25 weeks, and 52 weeks post grafting]
Skin biopsies will be obtained to observe physical development of the anchoring fibrils using electron microscopy
Eligibility Criteria
Criteria
Inclusion Criteria:
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Clinical diagnosis of recessive dystrophic epidermolysis bullosa (RDEB)
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13 years old or older and willing and able to give assent/consent
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Confirmation of RDEB diagnosis by immunofluorescence (IF) and electron microscopy (EM)
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NC1[+] and mAb LH24 antibody staining negative
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RDEB type VII collagen mutations in subject and carrier parents confirmed
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At least 100 to 200 cm2 areas of open erosions on the trunk and/or extremities suitable for skin grafting
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Able to undergo adequate anesthesia to allow grafting procedures to take place.
Exclusion Criteria:
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Medical instability limiting ability to travel to Stanford University Medical Center
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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.
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Antibodies to type VII collagen associated antigens
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Active infection in the area that will undergo grafting
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Evidence of systemic infection
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Current evidence or a history of squamous cell carcinoma in the area that will undergo grafting
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Active drug or alcohol addiction
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Hypersensitivity to vancomycin or amikacin
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Receipt of chemical or biological study product for the specific treatment of RDEB in the past six months
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Positive pregnancy test or breast-feeding
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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:
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Albumin < 2.5 g/dL
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Leukocytes > 20K/uL
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Hemoglobin < 7.5 g/dL. Low hemoglobin will be treated at the discretion of the investigators and the EB physician.
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Additional exceptions may be made at the discretion of the investigators and the EB physician.
- 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:
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Anorexia, can enroll up to Grade 4 (inclusive)
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Constipation, can enroll up to Grade 2 (inclusive)
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Dysphagia, can enroll up to Grade 4 (inclusive)
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Keratitis, can enroll up to Grade 4 (inclusive)
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Bone pain, can enroll up to Grade 2 (inclusive)
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Additional exceptions may be made at the discretion of the investigators and the EB physician.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stanford University School of Medicine | Stanford | California | United States | 94305 |
Sponsors and Collaborators
- Stanford University
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Abeona Therapeutics, Inc
Investigators
- Principal Investigator: Jean Tang, MD, PhD, Stanford University
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- Stanford Dermatology Website: EB Research Update
- Safety and Wound Outcomes Following Genetically Corrected Autologous Epidermal Grafts in Patients With Recessive Dystrophic Epidermolysis Bullosa.
Publications
None provided.- SU-10202010-7130
- IND# 13708
- R01AR055914
- RAC Protocol # 0701-827
- eProtocol 14563