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

To evaluate and further characterize the safety of EB-101 (LZRSE-Col7A1 gene-corrected keratinocyte sheets with type VII collagen [C7] expression) for the treatment of large, chronic DEB wounds in new and previously EB-101 treated patients 12 months and older.

Study Overview

• Status: Active, not recruiting
• Conditions: Epidermolysis Bullosa; Recessive Dystrophic Epidermolysis Bullosa; RDEB
• Intervention / Treatment: Biological: EB-101 Surgical application of RDEB wounds

Detailed Description

A multicenter, open-label, single-arm Phase 3b safety study of one-time surgical application of up to 12 autologous, LZRSE-Col7A1 gene-corrected keratinocyte sheets with C7 expression (EB-101) for the treatment of large, chronic DEB wounds in each of approximately 10-12 patients. Patients enrolled will also contribute biopsies to support manufacturing requirements. All patients will be followed through 24 weeks post-treatment.

Patients will be evaluated at their Screening Visit (D -60 to D -25), 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 inpatient medical facility that will allow appropriate immobilization of treated wounds, as determined by the Investigator, for observation for up to 7 days (±2 days) following treatment. They 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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Redwood City, California, United States, 94063
      • Stanford University
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • University of Massachusetts Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Clinical diagnosis of DEB.
2. Age 12 months and older.
3. Willing and able to give consent/assent; if under the age of 18 years, guardian(s) is/are willing and able to give consent.
4. (This inclusion criterion was deleted as of Amendment 1.)
5. Confirmation of DEB diagnosis (either dominant [DDEB] or recessive [RDEB] forms) by genetic testing.
6. Able to undergo adequate anesthesia during EB-101 treatment.
7. 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.
8. On stable pain medication regimen for at least 30 days prior to Screening (and through Baseline).

9. Must have at least one wound site that meets all of the following criteria:

   1. An area ≥20 cm2,
   2. Present for ≥6 months, and
   3. 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.
10. For patients with RDEB, they must have had Vyjuvek exposure by the time of screening or positive anti-C7 antibodies at baseline.
11. Patients must be willing to discontinue Vyjuvek and Filsuvez use on EB-101 treated sites until completion of the Week 24 visit.

Exclusion Criteria:

1. Medical instability limiting ability to travel to the study site or undergo EB-101 treatment.
2. 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.
3. (This exclusion criterion was deleted as of Amendment 3.)
4. Evidence of systemic infection.
5. Current evidence or a history of SCC in the area that will undergo EB-101 application.
6. Active drug or alcohol addiction.
7. Hypersensitivity to vancomycin or amikacin.
8. Receipt of chemical or biological investigational therapy for the specific treatment of DEB in the 3 months prior to EB-101 application.
9. Breast-feeding.
10. Inability to properly follow protocol assessments and protect keratinocyte sheet sites as determined by the PI.
11. Grade 3 clinical event or laboratory abnormality at Day 0. Abnormalities such as esophageal strictures, anemia, low albumin, and pain/itch are expected in severe DEB patients, and these abnormalities will not exclude a patient.
12. Unwillingness or inability to provide 4 skin biopsies, or patient's keratinocytes cannot be manufactured for use in EB-101 application.
13. Any other circumstance where the PI believes that the patient may not be appropriate for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EB-101 Surgical application of RDEB wounds; New or Previously Treated RDEB Patients	Biological: EB-101 Surgical application of RDEB wounds; 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]; Other Names: pz-cel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Endpoint (number of treatment-related and treatment-emergent adverse events (AEs) and serious adverse events (SAEs)	The number of treatment-related and treatment-emergent adverse events (TEAEs), treatment-emergent wound adverse events (TEWAEs), and serious adverse events (SAEs), including systemic and wound-specific adverse events.	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 (AE).	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 (SAE).	6 months
Safety Endpoint (Incidence of squamous cell carcinoma)	The incidence of squamous cell carcinoma (SCC).	6 months
Safety Endpoint RCR status	Replication-competent retrovirus (RCR) status.	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extent of pain reduction assessed by the Wong-Baker FACES scale	Extent of pain reduction assessed by the Wong-Baker FACES scale (for patients ages ≥6 years old) at Weeks 8, 12, and 24.	6 months
Longitudinal change in scores of Worst Itch Numeric Rating Scale	Longitudinal change in scores of Worst Itch Numeric Rating Scale (WI-NRS; for patients ages ≥6 years old) scores assessed at Weeks 8, 12, and 24	6 months
Longitudinal change of Zarit Burden Interview Short Form	Longitudinal change of Zarit Burden Interview Short Form (ZBI-12) for caregiver scores related to wound care, assessed at Weeks 12 and 24 (for all ages).	6 months
Change in Quality of Life in Epidermolysis Bullosa	Change in Quality of Life in Epidermolysis Bullosa (QOLEB) scores assessed at Week 24 compared with pretreatment Baseline scores (completed by patients ≥11 years old or with guidance for patients 8 to 10 years old). If patient is <8 years old, QOLEB should be completed by a legal guardian.	6 months
Change in Caregiver Global Impression of Pain	Change in Caregiver Global Impression of Pain (CrGI-Pain) scores assessed at Weeks 8, 12, and 24 compared with pretreatment Baseline (for all ages).	6 months
Comparison of how non-collagenous region 1 of the collagen VII molecule	Comparison of how non-collagenous region 1 of the collagen VII molecule (NC1) status relates to wound healing and safety profile (if applicable).	6 months
Comparison of how circulating C7 antibody status relates to wound healing and safety profile	Comparison of how circulating C7 antibody status relates to wound healing and safety profile (if applicable).	6 months
Proportion of RDEB wounds with ≥50%, ≥75%, and complete	Proportion of RDEB wounds with ≥50%, ≥75%, and complete (i.e., re epithelialization with no drainage or erosion and presence of only minor crusting) healing at Weeks 12 and 24, as determined by direct Investigator assessment.	6 months

Collaborators and Investigators

• Sponsor: Abeona Therapeutics, Inc
• Investigators: Study Director: Angela Iheanacho, MS, Abeona Therapeutics, Inc; Study Director: Sarah Abdelwahab, MD, Abeona Therapeutics, Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2023
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: January 23, 2023
• First Submitted That Met QC Criteria: February 2, 2023
• First Posted (Actual): February 13, 2023

Study Record Updates

• Last Update Posted (Actual): June 27, 2025
• Last Update Submitted That Met QC Criteria: June 24, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Chronic wounds
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Connective Tissue Diseases; Skin Diseases; Congenital Abnormalities; Skin Diseases, Genetic; Skin Abnormalities; Skin Diseases, Vesiculobullous; Collagen Diseases; Epidermolysis Bullosa; Epidermolysis Bullosa Dystrophica
• Other Study ID Numbers: EB-101-CL-302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No