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Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa

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ClinicalTrials.gov Identifier: NCT01263379
Recruitment Status : Active, not recruiting
First Posted : December 20, 2010
Last Update Posted : February 8, 2019
Sponsor:
Collaborators:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Abeona Therapeutics, Inc
Information provided by (Responsible Party):
Jean Yuh Tang, Stanford University

Tracking Information
First Submitted Date  ICMJE December 15, 2010
First Posted Date  ICMJE December 20, 2010
Last Update Posted Date February 8, 2019
Actual Study Start Date  ICMJE October 5, 2010
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2018)
  • Percentage surface area of wound healing [ Time Frame: 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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 17, 2010)
  • Presence of anchoring fibrils [ Time Frame: Week 4 ]
  • Presence of type VII collagen [ Time Frame: Week 4 ]
  • Frequency of adverse events [ Time Frame: Week 52 ]
  • Presence of anchoring fibrils [ Time Frame: Week 12 ]
  • Presence of anchoring fibrils [ Time Frame: Week 52 ]
  • Presence of type VII collagen [ Time Frame: Week 12 ]
  • Presence of type VII collagen [ Time Frame: Week 52 ]
Change History Complete list of historical versions of study NCT01263379 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2018)
duration of type VII collagen production [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: January 18, 2018)
presence of anchoring fibrils [ Time Frame: 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
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa
Official Title  ICMJE 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Epidermolysis Bullosa Dystrophica
  • Epidermolysis Bullosa
Intervention  ICMJE 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 Name: LEAES
Study Arms  ICMJE Experimental: LEAES treatment
LZRSE-Col7A1 Engineered Autologous Epidermal Sheets (LEAES)
Intervention: Biological: LZRSE-Col7A1 Engineered Autologous Epidermal Sheets
Publications * Siprashvili Z, Nguyen NT, Gorell ES, Loutit K, Khuu P, Furukawa LK, Lorenz HP, Leung TH, Keene DR, Rieger KE, Khavari P, Lane AT, Tang JY, Marinkovich MP. Safety and Wound Outcomes Following Genetically Corrected Autologous Epidermal Grafts in Patients With Recessive Dystrophic Epidermolysis Bullosa. JAMA. 2016 Nov 1;316(17):1808-1817. doi: 10.1001/jama.2016.15588.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 23, 2016)
10
Original Estimated Enrollment  ICMJE
 (submitted: December 17, 2010)
12
Estimated Study Completion Date  ICMJE December 31, 2025
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 13 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01263379
Other Study ID Numbers  ICMJE SU-10202010-7130
IND# 13708 ( Other Identifier: FDA (Investigational New Drug Application) )
R01AR055914 ( U.S. NIH Grant/Contract )
RAC Protocol # 0701-827 ( Other Identifier: NIH Recombinant DNA Advisory Committee )
eProtocol 14563 ( Other Identifier: Stanford Institutional Review Board )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Results will be submitted to scientific journals for publication and presented at scientific meetings.
Responsible Party Jean Yuh Tang, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  • Abeona Therapeutics, Inc
Investigators  ICMJE
Principal Investigator: Jean Tang, MD, PhD Stanford University
PRS Account Stanford University
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP