Study of EB-101 for the Treatment of Recessive Dystrophic Epidermolysis Bullosa

Recessive Dystrophic Epidermolysis Bullosa Clinical Trial

— VITAL  

Official title:

VITAL: A Pivotal Phase 3 Study of EB-101 for the Treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB) (GENE TRANSFER)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03632265
• Other study ID #: 46946
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: October 1, 2018
• Est. completion date: March 31, 2021

Study information

• Verified date: August 2018
• Source: Stanford University
• Contact: Melissa Barriga
• Phone: 6507368033
• Email: mbarriga[@]stanford.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

VITAL is an open-label, Phase 3 study of one-time surgical application of at least 35 EB-101 grafts for the treatment of eligible, chronic open wound sites in up to 15 RDEB patients.

Patient wounds will be randomized to receive grafting or remain untreated (control). Up to 6 wound sites for EB 101 grafting and at least 1 untreated control wound site will be performed for each patient.

Description:

This research project involves transferring type VII collagen into RDEB patients' keratinocytes, which are the majority of the cells in the outer layer of skin. We plan to take biopsies, grow cells in the laboratory (in sterile dishes with special fluid that allows cells to grow and multiply) and then infect these cells with a virus that we have engineered to insert the type of collagen VII gene that functions normally. This is known as "gene transfer".

The virus is made so that it only delivers the collagen VII into skin cells and should not spread to other parts of the body. Blood and skin tests will verify that the virus is not spreading. We will then graft these corrected cells (EB-101) over wounds that have not healed for some time.

The corrected cells are grown into sheets of cells that look like a plastic film. We plan to graft the sheet of cells to wound sites.

Patients will not be able to choose which wounds will receive grafting. The investigator will identify wounds that are suitable for grafting. A computer program will determine which wounds to graft (this is called randomization).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 15
• Est. completion date: March 31, 2021
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

1. Clinical diagnosis of RDEB;

2. Age 6 years or older, willing and able to give consent/assent;

3. If under the age of 18, guardian(s) is/are willing and able to give consent;

4. NC1[+] - portion of collagen VII;

5. Two confirmed RDEB collagen VII mutations with recessive inheritance patterns (or confirmation that parents don't have any evidence of dominant disease);

6. At least 40 cm2 areas of chronically wounded areas on the trunk and/or arms/legs suitable for skin grafting (open wounds);

7. Able to undergo adequate anesthesia to allow grafting procedures to take place;

8. Must have at least 2 eligible wound sites;

a. Wound sites must: i. Have an area =20 cm2, ii. Present for =6 months, and iii. Stage 2 wound;

9. Women of childbearing potential must use a reliable birth control method for 6 months post treatment.

Exclusion Criteria:

1. Medical instability limiting ability to travel to Stanford University Medical Center;

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. Evidence of immune response to C7 by IIF;

4. Evidence of systemic infection;

5. Current evidence or a history of SCC in the area that will undergo grafting;

6. Active drug or alcohol addiction;

7. Hypersensitivity to vancomycin or amikacin;

8. Receipt of chemical or biological study product for the specific treatment of RDEB in the past 3 months;

9. Positive pregnancy test or breast-feeding;

10. Clinically significant medical or laboratory abnormalities as determined by the investigator and the EB physician;

11. Inability to properly follow protocol and protect graft sites, as determined by the investigator and the EB physician;

12. Grade 3 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 subject; and

13. Inability to culture subject's keratinocytes

Related Conditions & MeSH terms

• Epidermolysis Bullosa
• Epidermolysis Bullosa Dystrophica
• Recessive Dystrophic Epidermolysis Bullosa

Intervention

Biological:
• EB-101
EB-101 is comprised of RDEB keratinocytes isolated from the patient's skin biopsies and transduced with a virus containing functioning collagen VII.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Jean Yuh Tang	Abeona Therapeutics, Inc

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of EB-101 wound healing change per patient between baseline and 3 months; treated versus untreated wounds; intra-subject chronic wound sites	Wound healing change will be assessed and subsequently photographed and quantified using medical imaging software from Canfield Scientific.	3 months
Secondary	Investigator's Global Assessment (IGA) score	Investigator's impression of healing of each graft/control site; less than or equal to 50% or greater than 50%	3 months
Secondary	Durability	Proportion of EB-101 grafts with IGA score of =50% wound healing at 3 months that continue to have IGA score of =50%	6 months
Secondary	Patient global impression scale of change	Patient will be asked to access overall change;	3 months
Secondary	Median of patient's impression of pain at each graft/control site	Median will be calculated of patient reported outcome assessing the subject's impression of pain of each graft/control site using the Wong-Baker Scale	3 months
Secondary	Median of patient's impression of itch at each graft/control site	Median will be calculated of patient reported outcome assessing the subject's impression of itch of each graft/control site using the Itch Man Scale	3 months