EB-101 Treatment for New and Previously Treated Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB)

Study Overview
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Brief Summary
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To evaluate and further characterize the safety of EB-101 (LZRSECol7A1 Engineered Autologous Epidermal Sheets [LEAES]) for the treatment of RDEB wounds in new and previously EB-101 treated patients 6 years and older.

Detailed Description
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A Multicenter, open-label, single-arm Phase 3b safety study of one-time surgical application of up to 8 autologous, gene-corrected keratinocyte sheets (EB-101) for the treatment of RDEB wounds in approximately 10-12 patients. Patients enrolled will also contribute biopsies to support manufacturing requirements. Patients will be evaluated at their Day -26 Screening visit, a phone call approximately 14 days after screening, and at Baseline (Day -1) prior to treatment on Day 0. Patients will remain in the hospital, or other suitable medical facility, as determined by the investigator, for observation for up to 5 days (+/- 1 day) following treatment and will be evaluated by phone on Day 14, by telehealth visits on Weeks 4, 8, and 18, and by clinic visits on Weeks 12 and 24. All patients will be followed through 24 weeks post-treatment.

Official Title
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A Phase 3b Study for the Treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB) in New and Previously EB-101 Treated Patients

Conditions
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Epidermolysis Bullosa, Recessive Dystrophic Epidermolysis Bullosa, RDEB

Intervention / Treatment
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* Biological: EB-101 Surgical application of RDEB wounds


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of RDEB Age 6 years and older; Willing and able to give consent/assent; if under the age of 18 years, guardian(s) is/are willing and able to give consent; Positive expression of NC1+ amino-terminal fragment of C7 in the skin; Two confirmed RDEB C7 mutations with recessive inheritance patterns (or confirmation that parents don't have any evidence of dominant disease); Able to undergo adequate anesthesia during EB-101 treatment; All women of childbearing potential must have a negative urine pregnancy test and use a reliable birth control method throughout the duration of the study and for 24 Weeks post treatment; On stable pain medication regimen for at least 30 days prior to Screening; Must have at least one wound site that meets all of the following criteria: An area ≥20 cm2 Present for ≥6 months Stage 2 wound defined as an open skin wound with partial thickness loss of dermis that has not extended through the dermis into subcutaneous tissue Exclusion Criteria: Medical instability limiting ability to travel to the study site or undergo EB-101 treatment; The presence of medical illness expected to complicate participation and/or compromise the safety of this technique, such as active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; Evidence or history of immune response to C7 by indirect immunofluorescence (IIF) or enzyme-linked immunosorbent assay; Evidence of systemic infection; Current evidence or a history of squamous cell carcinoma (SCC) in the area that will undergo EB-101 application; Active drug or alcohol addiction; Hypersensitivity to vancomycin or amikacin; Receipt of chemical or biological investigational therapy for the specific treatment of RDEB in the 3 months prior to EB-101 application; Positive pregnancy test or breast-feeding; Inability to properly follow protocol assessments and protect keratinocyte sheet sites as determined by the Principal Investigator; Grade 3 clinical event or laboratory abnormality at Day 0. Abnormalities such as esophageal strictures, anemia, low albumin, and pain/itch are expected in RDEB patients, and these abnormalities will not exclude a patient; Unwillingness or inability to provide 4-biopsies or inability to manufacture patient's keratinocytes for use in EB-101 application.

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EB-101 Surgical application of RDEB wounds<br>New or Previously Treated RDEB Patients | Biological: EB-101 Surgical application of RDEB wounds<br>* EB-101 autologous RDEB keratinocytes isolated from skin biopsies and transduced with a recombinant retrovirus containing a full-length COL7A1 expression cassette for C7 Other Names: • LZRSE-Col7A1 Engineered Autologous Epidermal Sheets [LEAES]<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoint (number of treatment related adverse events (AEs) and serious adverse events (SAEs) | The number of treatment related adverse events (AEs) and serious adverse events (SAEs). | 6 months | 
| Safety Endpoint (number of patients and wounds that have an infection or any related adverse event.) | The number of patients and wounds that have an infection or any related adverse event. | 6 months | 
| Safety Endpoint (number of patients and wounds that result in hospitalization (serious adverse event ) | The number of patients and wounds that result in hospitalization (serious adverse event [SAE]). | 6 months | 
| Safety Endpoint (Incidence of squamous cell carcinoma) | Incidence of squamous cell carcinoma | 6 months | 
| Safety Endpoint | qPCR detection of replication competent retrovirus (RCR) infection in whole blood (detected/not detected) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic wounds