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Epidermolysis Bullosa DystrophicaPhase 1/2NCT01263379

Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa

A Phase 1/2 study testing LZRSE-Col7A1 Engineered Autologous Epidermal Sheets in people with Epidermolysis Bullosa Dystrophica and Epidermolysis Bullosa, run by Abeona Therapeutics, Inc at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 13 years and older
What is being tested?
LZRSE-Col7A1 Engineered Autologous Epidermal Sheets
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
5 Oct 2010to 9 Mar 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 13 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Clinical diagnosis of recessive dystrophic epidermolysis bullosa (RDEB)
  • 13 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.

Who cannot join

  • 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
Show all 22Show fewer
  • 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
  • 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.
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Stanford University, School of Medicine, Dept of Dermatology

    Redwood City, California, 94063

Other trials in United States

About this study

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)

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.

Read the 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.

Being tested
LZRSE-Col7A1 Engineered Autologous Epidermal Sheets
Keywords
gene transfer
Medical subject headings
Epidermolysis Bullosa Dystrophica, Epidermolysis Bullosa

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LZRSE-Col7A1 Engineered Autologous Epidermal SheetsBiological

    Also called LEAES

    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.

Study groups in NCT01263379
Study groupRoleWhat they receive
LEAES treatmentExperimentalLZRSE-Col7A1 Engineered Autologous Epidermal Sheets (LEAES)
Receives: Biological: LZRSE-Col7A1 Engineered Autologous Epidermal Sheets

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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

    Measured: 3, 6 and 12 months post grafting

Secondary outcomes (1)
  1. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Dec 2010 (estimated)
  2. Study start5 Oct 2010
  3. Primary completion9 Mar 2022
  4. Study completion9 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01263379
Sponsor's protocol ID
SU-10202010-7130
Other IDs
R01AR055914, RAC Protocol # 0701-827, eProtocol 14563
Status last verified
Aug 2023
First submitted
15 Dec 2010
Last updated
22 Aug 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Results will be submitted to scientific journals for publication and presented at scientific meetings.

Publications

  • 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.

    PubMed 36253825
  • 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.

    PubMed 31578311
  • 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.

    PubMed 27802546

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LZRSE-Col7A1 Engineered Autologous Epidermal Sheets in people with Epidermolysis Bullosa Dystrophica and Epidermolysis Bullosa, run by Abeona Therapeutics, Inc at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Wounds by Healing Category Per Investigator Visual Assessment (time frame: 3, 6, 12 and 24 months post grafting). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01263379, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2023.

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