Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa

Epidermolysis Bullosa Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01263379
• Other study ID #: SU-10202010-7130
• Secondary ID: R01AR055914RAC P
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 5, 2010
• Est. completion date: March 9, 2022

Study information

• Verified date: August 2023
• Source: Abeona Therapeutics, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 9, 2022
• Est. primary completion date: March 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Epidermolysis Bullosa
• Epidermolysis Bullosa Dystrophica

Intervention

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.

Locations

Country	Name	City	State
United States	Stanford University, School of Medicine, Dept of Dermatology	Redwood City	California

Sponsors (3)

Lead Sponsor	Collaborator
Abeona Therapeutics, Inc	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Presence of Anchoring Fibrils (AF)	Skin biopsies were obtained to observe physical development of the anchoring fibrils using electron microscopy	3 months, 6 months, 12 months and 24 months post grafting
Primary	Number of Wounds by Healing Category Per Investigator Visual Assessment	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.	3, 6, 12 and 24 months post grafting
Primary	Percentage Surface Area of Wound Healing	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	3, 6 and 12 months post grafting
Secondary	Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production	Skin biopsies were obtained to evaluate expression of type VII collagen, NC2 epitope, using immuno-electron microscopy and immuno-fluorescent light microscopy.	3 months, 6 months, 12 months, 24 months post-grafting

External Links

•   Safety and Wound Outcomes Following Genetically Corrected Autologous Epidermal Grafts in Patients With Recessive Dystrophic Epidermolysis Bullosa.
•   Stanford Dermatology Website: EB Research Update