Phase 3, Open-label Clinical Trial of EB-101 for the Treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB)

• ClinicalTrials.gov Identifier: NCT04227106
• Recruitment Status: Completed
• First Posted: January 13, 2020
• Last Update Posted: December 5, 2022
• Sponsor: Abeona Therapeutics, Inc
• Information provided by (Responsible Party): Abeona Therapeutics, Inc

Tracking Information

• First Submitted Date: January 10, 2020
• First Posted Date: January 13, 2020
• Last Update Posted Date: December 5, 2022
• Actual Study Start Date: January 10, 2020
• Actual Primary Completion Date: October 18, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 25, 2021)

• Wound Healing [ Time Frame: 24 weeks post-treatment ]
  Proportion of RDEB wound sites with ≥50% healing from Baseline in treated versus untreated wounds
• Pain Reduction [ Time Frame: 24 weeks post-treatment ]
  Associated with wound dressing change assessed by the mean differences in scores of the Wong-Baker FACES scale between treated and untreated wounds

Original Primary Outcome Measures (submitted: January 10, 2020)

Wound Healing [ Time Frame: 12 weeks post-treatment ]

Proportion of RDEB wound sites with ≥50% healing from Baseline in treated versus untreated intra-participant wound sites

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 3, Open-label Clinical Trial of EB-101 for the Treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB)
• Official Title: VIITAL: A Phase 3 Study of EB-101 for the Treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB)
• Brief Summary: The purpose of this trial is to evaluate safety and efficacy of surgical application of EB-101 (autologous, gene-corrected keratinocyte sheets) as a treatment of recessive dystrophic epidermolysis bullosa (RDEB).

Detailed Description

Recessive dystrophic epidermolysis bullosa (RDEB) is an ultra-rare, severe inherited blistering skin disease caused by the absence of a protein known as type 7 collagen (C7). There is no approved treatment for RDEB. Only supportive care is currently possible.

This open-label, controlled study will evaluate the efficacy and safety of EB-101 for the treatment of large, chronic, RDEB wounds. The study intervention consists of one-time surgical application of gene-corrected keratinocyte sheets (EB-101) for the treatment of RDEB wound sites in up to approximately 10-15 participants. A single EB-101 sheet is able to provide healing to a wound area up to approximately 40cm2. Up to 6 (six) EB-101 sheets may be applied to each patient, depending on the area of existing wounds. The co-primary endpoints of the study are: 1) the proportion of RDEB wound sites with greater than or equal to 50% healing from baseline, comparing treated with untreated wound sites at Week 24 (Month 6) as determined by direct investigator assessment; and 2) pain reduction associated with wound dressing change assessed by the mean differences in scores of the Wong-Baker FACES scale between treated and untreated wounds at Week 24 (Month 6). Patient-reported outcomes and safety will also be collected throughout the study.

The primary analysis for efficacy will be assessed when all patients reach Week 24. Safety and efficacy assessments will be conducted at regular intervals and completed when last patient reaches Week 26 post-treatment.

Upon completion of the study period, patients will be monitored annually as per standard of care for up to 15 years.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Epidermolysis Bullosa
• Recessive Dystrophic Epidermolysis Bullosa

Intervention

Biological: 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 Name: LZRSE-Col7A1 Engineered Autologous Epidermal Sheets [LEAES]

Study Arms

Experimental: EB-101

One-time surgical application of EB-101 on up to 6 chronic, RDEB wounds

Intervention: Biological: EB-101

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 2, 2022): 11
• Original Estimated Enrollment (submitted: January 10, 2020): 15
• Actual Study Completion Date: October 18, 2022
• Actual Primary Completion Date: October 18, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Clinical diagnosis of RDEB;
• Age 6 years or older, willing and able to give consent/assent;
• If under the age of 18, guardian(s) is/are willing and able to give consent;
• Positive expression of the non-collagenous region 1 of the type 7 collagen protein (NC1+) in the skin;
• Two confirmed RDEB C7 mutations with recessive inheritance patterns (or confirmation that parents don't have any evidence of dominant disease);
• At least 40 cm2 areas of chronically wounded area on the trunk and/or extremities suitable for EB-101 application (open erosions);
• Able to undergo adequate anesthesia during EB-101 application;

• Must have at least two matched, eligible wound sites (one pair);

  • Wound sites must:

    • Have an area ≥20 cm2,
    • Present for ≥6 months, and
    • Stage 2 wound;
• Women of childbearing potential must use a reliable birth control method throughout the duration of the study and for 6 months post treatment;
• Negative pregnancy test;
• Must be on stable pain medication regimen at least 30 days prior to Screening

Exclusion Criteria:

• Medical instability limiting ability to travel to the study site;
• 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 of immune response to C7 by indirect immunofluorescence (IIF);
• 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 study product for the specific treatment of RDEB in the past 3 months;
• Positive pregnancy test or breast-feeding;
• Clinically significant medical or laboratory abnormalities as determined by the Principal Investigator;
• Inability to properly follow protocol 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. These abnormalities will not exclude a participant; and
• Inability to culture participant's keratinocytes.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04227106
• Other Study ID Numbers: EB-101-CL-301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Abeona Therapeutics, Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Abeona Therapeutics, Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jean Tang, MD; Stanford University

• PRS Account: Abeona Therapeutics, Inc
• Verification Date: April 2022