Brief Title
Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa
Official Title
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)
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 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 Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Percentage surface area of wound healing
Secondary Outcome
duration of type VII collagen production
Condition
Epidermolysis Bullosa Dystrophica
Intervention
LZRSE-Col7A1 Engineered Autologous Epidermal Sheets
Study Arms / Comparison Groups
LEAES treatment
Description: LZRSE-Col7A1 Engineered Autologous Epidermal Sheets (LEAES)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
10
Start Date
October 5, 2010
Completion Date
December 31, 2025
Primary Completion Date
December 31, 2023
Eligibility Criteria
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.
Gender
All
Ages
13 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Jean Tang, MD, PhD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01263379
Organization ID
SU-10202010-7130
Secondary IDs
IND# 13708
Responsible Party
Principal Investigator
Study Sponsor
Stanford University
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Study Sponsor
Jean Tang, MD, PhD, Principal Investigator, Stanford University
Verification Date
October 2020