Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Stanford University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alfred Lane, Stanford University
ClinicalTrials.gov Identifier:
NCT01263379
First received: December 15, 2010
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited blistering skin disease caused by absence of a protein known as type VII collagen. Patients with RDEB develop large, severely painful blisters and open wounds from minor trauma to their skin. This trial will create a graft, which the investigators call "LEAES," of the patient's own skin that has been genetically engineered in the investigators lab to express this missing protein. The purpose of this study is to achieve proof-of-concept for this general approach to cell-based gene therapy in humans and to set the stage for further therapeutic extension in RDEB. The investigators will basically take a subject's own cells, correct them in culture, and then transplant the corrected cells back onto them.


Condition Intervention Phase
Epidermolysis Bullosa Dystrophica
Epidermolysis Bullosa
Genetic: LZRSE-Col7A1 Engineered Autologous Epidermal Sheets (LEAES)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Single Center Trial of Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Using the Drug LZRSE-Col7A1 Engineered Autologous Epidermal Sheets (LEAES)

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Presence of anchoring fibrils [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  • Presence of type VII collagen [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  • Frequency of adverse events [ Time Frame: Week 52 ] [ Designated as safety issue: Yes ]
  • Presence of anchoring fibrils [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Presence of anchoring fibrils [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
  • Presence of type VII collagen [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Presence of type VII collagen [ Time Frame: Week 52 ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: December 2010
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Genetic: LZRSE-Col7A1 Engineered Autologous Epidermal Sheets (LEAES)
    Recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited blistering skin disease caused by absence of a protein known as type VII collagen. 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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Clinical diagnosis of recessive dystrophic epidermolysis bullosa (RDEB)
  2. 18 years old or older and willing and able to give 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 demonstrated on enzyme linked immunosorbent assay (ELISA)
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01263379

Contacts
Contact: Priya V Hegde, MS (650) 724-1982 phegde@stanford.edu
Contact: Kylie Loutit (650) 721-7166 kloutit@stanford.edu

Locations
United States, California
Stanford University School of Medicine Recruiting
Stanford, California, United States, 94305
Contact: Priya V Hegde, MS    650-724-1982    phegde@stanford.edu   
Contact: Kylie Loutit    (650) 721-7166    kloutit@stanford.edu   
Principal Investigator: M. Peter Marinkovich M.D.         
Principal Investigator: Paul A. Khavari         
Principal Investigator: Alfred T Lane         
Principal Investigator: Phuong Khuu, MD         
Sub-Investigator: Peter Lorenz, MD         
Sub-Investigator: Louise Furukawa, MD         
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Alfred T Lane Stanford University
  More Information

Additional Information:
No publications provided

Responsible Party: Alfred Lane, Professor of Dermatology and Pediatrics, Stanford University
ClinicalTrials.gov Identifier: NCT01263379     History of Changes
Other Study ID Numbers: SU-10202010-7130, IND# 13708, R01AR055914, RAC Protocol # 0701-827, eProtocol 14563
Study First Received: December 15, 2010
Last Updated: August 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Stanford University:
gene transfer

Additional relevant MeSH terms:
Epidermolysis Bullosa
Epidermolysis Bullosa Dystrophica
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous
Collagen Diseases
Connective Tissue Diseases

ClinicalTrials.gov processed this record on September 29, 2014