EB-101 for Epidermolysis Bullosa

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

12 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment EB-101 for Epidermolysis Bullosa?

Research on similar gene therapies for Epidermolysis Bullosa shows promise, with studies demonstrating long-term restoration of type VII collagen, which is crucial for skin integrity, in preclinical models. These findings suggest that gene delivery methods, like those used in EB-101, can effectively correct genetic defects in skin tissue, potentially improving symptoms in patients. ^{1 2 3 4 5}

Is EB-101 safe for use in humans?

The treatment involving gene-modified cells, similar to EB-101, was well tolerated in a study with no serious adverse reactions or autoimmune responses observed, suggesting it is generally safe in humans. ^{1 2 3 4 5}

How is the treatment EB-101 unique for epidermolysis bullosa?

EB-101 is unique because it involves using a patient's own skin cells that are genetically modified to correct the COL7A1 gene mutation, which is responsible for the skin fragility in epidermolysis bullosa. This ex-vivo gene therapy approach aims to restore the production of type VII collagen, a key structural protein, directly addressing the root cause of the condition rather than just alleviating symptoms. ^{1 3 4 6 7}

What is the purpose of this trial?

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.

Research Team

Angela Iheanacho, MS

Principal Investigator

Abeona Therapeutics, Inc

Sarah Abdelwahab, MD

Principal Investigator

Abeona Therapeutics, Inc

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

BP180 gene delivery in junctional epidermolysis bullosa. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Long-term type VII collagen restoration to human epidermolysis bullosa skin tissue. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

SIN retroviral vectors expressing COL7A1 under human promoters for ex vivo gene therapy of recessive dystrophic epidermolysis bullosa. [2021]

5. England pubmed.ncbi.nlm.nih.gov

An RNA-targeted therapy for dystrophic epidermolysis bullosa. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Gene therapy of epidermolysis bullosa. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Fibroblasts show more potential as target cells than keratinocytes in COL7A1 gene therapy of dystrophic epidermolysis bullosa. [2012]