Clinical trial NCT05725018: EB-101 Treatment for New and Previously Treated Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Official title: A Phase 3b Study for the Treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB) in New and Previously EB-101 Treated Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Epidermolysis Bullosa
Recessive Dystrophic Epidermolysis Bullosa
RDEB
Keywords: Chronic wounds
Lead sponsor: Abeona Therapeutics, Inc
Sponsor class: INDUSTRY
First posted: 2023-02-13
Enrollment: 12
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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 RDEB wounds in new and previously EB-101 treated patients 12 months and older.

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 RDEB 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.

Eligibility criteria: Inclusion Criteria:

1. Clinical diagnosis of RDEB.
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. Two confirmed RDEB C7 mutations with recessive inheritance patterns (or confirmation that parents don't have any evidence of dominant disease).
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.

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 RDEB 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 RDEB 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.

Primary outcomes:
measure: Safety Endpoint (number of treatment-related and treatment-emergent adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 6 months
measure: Safety Endpoint (number of patients and wounds that have an infection or any related adverse event.)
timeFrame: 6 months
measure: Safety Endpoint (number of patients and wounds that result in hospitalization (serious adverse event )
timeFrame: 6 months
measure: Safety Endpoint (Incidence of squamous cell carcinoma)
timeFrame: 6 months
measure: Safety Endpoint RCR status
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
measure: Proportion of RDEB wounds with ≥50%, ≥75%, and complete
timeFrame: 6 months
measure: Extent of pain reduction assessed by the Wong-Baker FACES scale
timeFrame: 6 months
measure: Longitudinal change in scores of Worst Itch Numeric Rating Scale
timeFrame: 6 months
measure: Longitudinal change of Zarit Burden Interview Short Form
timeFrame: 6 months
measure: Change in Quality of Life in Epidermolysis Bullosa
timeFrame: 6 months
measure: Change in Caregiver Global Impression of Pain
timeFrame: 6 months
measure: Comparison of how non-collagenous region 1 of the collagen VII molecule
timeFrame: 6 months
measure: Comparison of how circulating C7 antibody status relates to wound healing and safety profile
timeFrame: 6 months
Locations:
city: Redwood City
country: United States
facility: Stanford University
state: California
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
Study officials:
affiliation: Abeona Therapeutics, Inc
name: Angela Iheanacho, MS
role: STUDY_DIRECTOR
affiliation: Abeona Therapeutics, Inc
name: Sarah Abdelwahab, MD
role: STUDY_DIRECTOR
References: