Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa

NCT01263379 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: SU-10202010-7130R01AR055914RAC Protocol # 0701-827eProtocol 14563
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Epidermolysis Bullosa Dystrophica; Epidermolysis Bullosa

Keywords

gene transfer

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (1)

• Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production

  3 months, 6 months, 12 months, 24 months post-grafting

Other Outcomes (1)

• Number of Participants With Presence of Anchoring Fibrils (AF)

  3 months, 6 months, 12 months and 24 months post grafting

Study Arms (1)

LEAES treatment

EXPERIMENTAL

LZRSE-Col7A1 Engineered Autologous Epidermal Sheets (LEAES)

Biological: LZRSE-Col7A1 Engineered Autologous Epidermal Sheets

Interventions

LZRSE-Col7A1 Engineered Autologous Epidermal Sheets BIOLOGICAL

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.

Also known as: LEAES

LEAES treatment

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of recessive dystrophic epidermolysis bullosa (RDEB)
• years old or older and willing and able to give assent/consent
• Confirmation of RDEB diagnosis by immunofluorescence (IF) and electron microscopy (EM)
• NC1\[+\] and mAb LH24 antibody staining negative
• RDEB type VII collagen mutations in subject and carrier parents confirmed
• At least 100 to 200 cm2 areas of open erosions on the trunk and/or extremities suitable for skin grafting
• Able to undergo adequate anesthesia to allow grafting procedures to take place.

You may not qualify if:

• Medical instability limiting ability to travel to Stanford University Medical Center
• 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.
• Antibodies to type VII collagen associated antigens
• Active infection in the area that will undergo grafting
• Evidence of systemic infection
• Current evidence or a history of squamous cell carcinoma in the area that will undergo grafting
• Active drug or alcohol addiction
• Hypersensitivity to vancomycin or amikacin
• Receipt of chemical or biological study product for the specific treatment of RDEB in the past six months
• Positive pregnancy test or breast-feeding
• 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.
• 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:

Sponsors & Collaborators

• Abeona Therapeutics, Inc: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator
• Stanford University: collaborator

Study Sites (1)

Stanford University, School of Medicine, Dept of Dermatology

Redwood City, California, 94063, United States

Location

Related Publications (3)

• So JY, Nazaroff J, Iwummadu CV, Harris N, Gorell ES, Fulchand S, Bailey I, McCarthy D, Siprashvili Z, Marinkovich MP, Tang JY, Chiou AS. Long-term safety and efficacy of gene-corrected autologous keratinocyte grafts for recessive dystrophic epidermolysis bullosa. Orphanet J Rare Dis. 2022 Oct 17;17(1):377. doi: 10.1186/s13023-022-02546-9.

  PMID: 36253825 DERIVED

• Eichstadt S, Barriga M, Ponakala A, Teng C, Nguyen NT, Siprashvili Z, Nazaroff J, Gorell ES, Chiou AS, Taylor L, Khuu P, Keene DR, Rieger K, Khosla RK, Furukawa LK, Lorenz HP, Marinkovich MP, Tang JY. Phase 1/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa. JCI Insight. 2019 Oct 3;4(19):e130554. doi: 10.1172/jci.insight.130554.

  PMID: 31578311 DERIVED

• 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.

  PMID: 27802546 DERIVED

Related Links

• Safety and Wound Outcomes Following Genetically Corrected Autologous Epidermal Grafts in Patients With Recessive Dystrophic Epidermolysis Bullosa.

MeSH Terms

Conditions

Epidermolysis Bullosa Dystrophica; Epidermolysis Bullosa

Condition Hierarchy (Ancestors)

Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Skin Diseases, Vesiculobullous

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Abeona Therapeutics

clinicalresults@abeonatherapeutics.com

(216) 282-8150

Study Officials

• Jean Tang, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2010
• First Posted: December 20, 2010
• Study Start: October 5, 2010
• Primary Completion: March 9, 2022
• Study Completion: March 9, 2022
• Last Updated: August 22, 2023
• Results First Posted: July 10, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Study protocol is attached to this submission and will be available per ClinicalTrials.gov timeline.

Locations

US (1)