EB-101 for Epidermolysis Bullosa

Not currently recruiting at 1 trial location

Overseen By Abeona Therapeutics

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Abeona Therapeutics, Inc

Must be taking: Pain medications

Must not be taking: Investigational therapies

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 22

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called EB-101 for a rare skin condition known as epidermolysis bullosa (EB), specifically focusing on dystrophic epidermolysis bullosa (DEB). EB-101 is an experimental treatment involving ex-vivo-expanded autologous keratinocytes transduced with a retroviral vector containing the COL7A1 gene. The trial aims to assess the safety and effectiveness of EB-101 in healing large, long-lasting wounds in individuals, regardless of prior use of this treatment. Ideal candidates have a confirmed DEB diagnosis, a wound open for over six months, and a size greater than 20 cm². Participants must tolerate anesthesia and have stable pain management. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable pain medication regimen for at least 30 days before starting and throughout the study. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that EB-101, also known as prademagene zamikeracel, is a gene therapy being tested to treat wounds in people with recessive dystrophic epidermolysis bullosa (DEB). In studies using EB-101, the treatment appeared safe. Patients had their own skin cells altered to address the underlying problem of their condition, and these cells were then placed back onto their wounds.

Previous studies found that patients generally tolerated EB-101 well. No major safety issues were widely reported, and researchers have studied the treatment for its long-term effects. This therapy aims to heal large and chronic wounds by using the patient’s own cells, reducing the risk of rejection. While EB-101 is still under investigation for this specific use, available data suggest it is a promising and safe option for those eligible for the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Epidermolysis Bullosa?

EB-101 is unique because it offers a new approach to treating Epidermolysis Bullosa (EB) by using gene-corrected autologous keratinocytes. This means it targets the root cause of the condition by directly addressing the genetic defect in the patient’s skin cells. Unlike traditional treatments that focus on managing symptoms or protecting the skin, EB-101 aims to heal the wounds by restoring the missing or defective protein. Researchers are excited because this method could provide a long-lasting, potentially curative solution for patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB), offering hope beyond the current standard of care.

What evidence suggests that EB-101 is effective for treating Epidermolysis Bullosa?

Research shows that EB-101, also known as ZEVASKYN, effectively treats wounds in people with recessive dystrophic epidermolysis bullosa (RDEB). This treatment uses the patient's own skin cells, repaired with gene therapy, to create sheets placed on wounds. Studies have found that this method helps the skin produce type VII collagen, a protein often lacking or faulty in RDEB patients, leading to better wound healing. The data supporting its effectiveness has led to its approval for use in both adults and children with large, long-lasting wounds caused by this condition. Evidence suggests promising results in closing and healing wounds, making EB-101 an important option for those affected by RDEB.

In this trial, participants will receive the EB-101 treatment through surgical application to RDEB wounds, evaluating its effectiveness in new or previously treated RDEB patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Angela Iheanacho, MS

Principal Investigator

Abeona Therapeutics, Inc

Sarah Abdelwahab, MD

Principal Investigator

Abeona Therapeutics, Inc

Are You a Good Fit for This Trial?

This trial is for patients aged 6 and older with Recessive Dystrophic Epidermolysis Bullosa (RDEB) who have stable pain medication regimens and at least one wound larger than 20 cm2 that's been present for over six months. Participants must not be pregnant, use reliable birth control, and cannot have a history of certain allergies or recent investigational therapies.

Inclusion Criteria

I have two confirmed RDEB C7 mutations inherited recessively.

I have a wound larger than 20 cm2, present for over 6 months, and it's a stage 2 wound.

I am using reliable birth control and have a negative pregnancy test.

Exclusion Criteria

I have severe symptoms or lab results, but common issues like throat tightness, low iron, low protein, or pain/itch won't disqualify me.

I am too unwell to travel for treatment or participate in the study.

You are currently addicted to drugs or alcohol.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

5 weeks

1 visit (in-person), 1 phone call

Treatment

One-time surgical application of up to 12 autologous, gene-corrected keratinocyte sheets

1 week

Inpatient stay for up to 7 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Phone call on Day 14; telehealth visits on Weeks 4, 8, and 18; clinic visits on Weeks 12 and 24

What Are the Treatments Tested in This Trial?

Interventions

• EB-101
• Surgical application of RDEB wounds

Trial Overview The trial tests EB-101, which are engineered skin sheets applied surgically to treat wounds caused by RDEB. It aims to assess the safety of this treatment in both new patients and those previously treated with EB-101.

How Is the Trial Designed?

Group I: EB-101 Surgical application of RDEB wounds Experimental Treatment 1 Intervention

New or Previously Treated RDEB Patients

EB-101 is already approved in United States for the following indications:

Approved in United States as Prademagene zamikeracel for:

• Recessive dystrophic epidermolysis bullosa (RDEB)

Who Is Running the Clinical Trial?

Abeona Therapeutics, Inc

Lead Sponsor

Trials

12

Recruited

1,100+

Published Research Related to This Trial

The study established an efficient method for introducing the COL7A1 gene into skin cells from patients with dystrophic epidermolysis bullosa (DEB), showing that gene transfer can restore collagen VII expression in these cells.

Skin graft experiments indicated that gene-transferred fibroblasts produced more collagen VII at the dermal-epidermal junction than keratinocytes, suggesting that targeting fibroblasts may be a more effective approach for gene therapy in treating DEB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibroblasts show more potential as target cells than keratinocytes in COL7A1 gene therapy of dystrophic epidermolysis bullosa. Goto, M., Sawamura, D., Ito, K., et al.[2012]

Initial gene therapy experiments for epidermolysis bullosa (EB) have successfully corrected genetic defects in vitro and in animal models, particularly for junctional EB caused by mutations in laminin-5 and type XVII collagen.

Despite promising results in laboratory settings, these gene therapy approaches have not yet progressed to successful Phase I clinical trials in EB patients, prompting researchers to explore alternative methods like splicing modulation for potential treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy of epidermolysis bullosa. Bauer, JW., Laimer, M.[2023]

Ex vivo gene transfer using minimal self-inactivating retroviral vectors to correct COL7A1 in epidermal stem cells shows promise for treating recessive dystrophic epidermolysis bullosa (RDEB), with successful genetic correction of skin cells from patients.

The study demonstrated long-term expression of type VII collagen and restored skin adherence in human skin equivalents grafted onto mice, indicating potential for effective treatment in patients with RDEB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SIN retroviral vectors expressing COL7A1 under human promoters for ex vivo gene therapy of recessive dystrophic epidermolysis bullosa. Titeux, M., Pendaries, V., Zanta-Boussif, MA., et al.[2021]

A new gene delivery method using retroviral vectors has shown long-term success in restoring type VII collagen in skin tissue affected by recessive dystrophic epidermolysis bullosa (RDEB), maintaining expression for over a year and through 12 skin turnover cycles.

This restoration corrected key features of RDEB, such as the formation of anchoring fibrils, indicating that this approach is both effective and safe, paving the way for future human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term type VII collagen restoration to human epidermolysis bullosa skin tissue. Siprashvili, Z., Nguyen, NT., Bezchinsky, MY., et al.[2021]

RNA trans-splicing has been successfully demonstrated as a potential treatment for recessive dystrophic epidermolysis bullosa (RDEB) by correcting type VII collagen mutations in patient-derived keratinocytes, showing effective protein secretion in a pre-clinical mouse model.

The study indicates that using a self-inactivating lentiviral vector for RNA trans-splicing can lead to long-term correction of the RDEB phenotype, as evidenced by the strong expression of human type VII collagen in grafted skin on immunodeficient mice after 12 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An RNA-targeted therapy for dystrophic epidermolysis bullosa. Peking, P., Koller, U., Duarte, B., et al.[2018]

In a phase I trial involving 4 adults with recessive dystrophic epidermolysis bullosa (RDEB), gene-modified fibroblasts were safely administered with no serious adverse or autoimmune reactions observed over 12 months.

The treatment led to a significant increase in type VII collagen (C7) expression in the injected skin of 3 out of 4 subjects, indicating potential efficacy for restoring skin integrity, with sustained effects noted in 2 subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa. Lwin, SM., Syed, F., Di, WL., et al.[2022]

A retroviral vector was successfully used to deliver the wild-type BP180 gene to keratinocytes from patients with junctional epidermolysis bullosa (JEB), restoring BP180 protein expression and normalizing cell adhesion in vitro.

When these genetically modified keratinocytes were used to regenerate skin on immune-deficient mice, the resulting tissue showed restored BP180 expression at the dermal-epidermal junction, indicating potential for future gene therapy approaches in treating JEB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BP180 gene delivery in junctional epidermolysis bullosa. Seitz, CS., Giudice, GJ., Balding, SD., et al.[2023]

Citations

1. fda.gov fda.gov/media/186796/download

ZEVASKYN This document summarizes the basis of approval of ZEVASKYN for treatment of wounds in recessive dystrophic epidermolysis bullosa (RDEB).

2. investors.abeonatherapeutics.com investors.abeonatherapeutics.com/press-releases/detail/325/abeona-therapeutics-announces-permanent-j-code-for

Abeona Therapeutics® Announces Permanent J-Code for ... Abeona's ZEVASKYN® (prademagene zamikeracel) is the first and only autologous cell-based gene therapy for the treatment of wounds in adults and ...

3. go.drugbank.com go.drugbank.com/drugs/DB17895

Prademagene zamikeracel: Uses, Interactions, Mechanism ... Prademagene zamikeracel is a gene therapy used to treat wounds associated with recessive dystrophic epidermolysis bullosa.

4. bookcafe.yuntsg.com bookcafe.yuntsg.com/ueditor/jsp/upload/file/20250722/1753170209282019541.pdf

Prademagene zamikeracel for recessive dystrophic ... Prademagene zamikeracel is an autologous sheet of COL7A1 gene-corrected keratinocytes that aims to address the unmet clinical need in large, ...

5. zevaskynhcp.com zevaskynhcp.com/treatment-overview/

Treatment Overview ZEVASKYN™ (prademagene zamikeracel) is an autologous cell sheet-based gene therapy indicated for the treatment of wounds in adult and pediatric patients with ...

6. ema.europa.eu ema.europa.eu/en/medicines/human/orphan-designations/eu-3-17-1835

orphan designation for treatment of epidermolysis bullosa This medicine is prepared individually for patients who have epidermolysis bullosa due to mutations in the COL7A1 gene.