Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa

Registration Number
NCT01263379
Lead Sponsor
Abeona Therapeutics, Inc
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.

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 gen...

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
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.
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
LEAES treatmentLZRSE-Col7A1 Engineered Autologous Epidermal SheetsLZRSE-Col7A1 Engineered Autologous Epidermal Sheets (LEAES)
Primary Outcome Measures
NameTimeMethod
Number of Wounds by Healing Category Per Investigator Visual Assessment3, 6, 12 and 24 months post grafting

The graft site was clinically evaluated by the investigator with a global score of: 1) 100% to 75% healed, 2) 74% to 50% healed, 3) 49% or less healed with 100% meaning completely healed.

Percentage Surface Area of Wound Healing3, 6 and 12 months post grafting

Percentage of wound area 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

Secondary Outcome Measures
NameTimeMethod
Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production3 months, 6 months, 12 months, 24 months post-grafting

Skin biopsies were obtained to evaluate expression of type VII collagen, NC2 epitope, using immuno-electron microscopy and immuno-fluorescent light microscopy.

Trial Locations

Locations (1)

Stanford University, School of Medicine, Dept of Dermatology

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Redwood City, California, United States

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