Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa

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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