ALLO-ASC-SHEET for Epidermolysis Bullosa

Overseen By Fernanda Bellodi Schmidt

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Anterogen Co., Ltd.

Must not be taking: Antibiotics

Disqualifiers: Pregnancy, Breastfeeding, Others

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

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: 12

Duration: 12 weeks

6 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ALLO-ASC-SHEET for individuals with dystrophic epidermolysis bullosa, a condition that causes fragile skin and painful blisters. The study compares two treatments: ALLO-ASC-SHEET, which uses adipose-derived stem cells, and a regular hydrogel sheet. The trial aims to determine which treatment more effectively heals skin ulcers. It seeks participants with confirmed dystrophic epidermolysis bullosa who have two similar, non-infected skin ulcers. As a Phase 2 trial, it focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you require antibiotics for a bacterial infection on the target skin ulcer area, you may be excluded from the trial.

Is there any evidence suggesting that ALLO-ASC-SHEET is likely to be safe for humans?

Research shows that ALLO-ASC-SHEET is generally safe and well-tolerated. Previous studies with similar treatments, such as ALLO-ASC-DFU, indicate that these hydrogel sheets, containing special cells that help repair damaged tissue, can reduce swelling and irritation.

These special cells, called adipose-derived stem cells, come from fat tissue and have been safely used in treatments for skin wounds. Most patients experience only mild side effects. Additionally, researchers are currently testing ALLO-ASC-SHEET in a mid-stage trial, indicating some earlier evidence of its safety.

Overall, while more research is needed, early findings suggest that ALLO-ASC-SHEET is safe for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard care options for Epidermolysis Bullosa, which typically involve conventional wound dressings, ALLO-ASC-SHEET is unique because it uses allogeneic mesenchymal stem cells. These stem cells offer a new mechanism of action by potentially promoting healing and tissue regeneration directly at the wound site. Researchers are excited about this treatment as it could provide a more proactive healing approach, possibly improving outcomes for patients with this challenging condition.

What evidence suggests that ALLO-ASC-SHEET might be an effective treatment for Epidermolysis Bullosa?

Research has shown that ALLO-ASC-SHEET, one of the treatments studied in this trial, might help treat wounds in people with epidermolysis bullosa, a condition that makes the skin very fragile. This treatment uses special cells from fat tissue, which can transform into different cell types to repair damaged skin. Studies have found that these cells can reduce inflammation and aid in healing wounds in various skin conditions. Although more research is needed, early results suggest that ALLO-ASC-SHEET could be promising in managing and healing the difficult wounds caused by this condition. Participants in this trial may receive either ALLO-ASC-SHEET or a conventional therapy as a control. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals with dystrophic epidermolysis bullosa, confirmed by specific tests. Participants must have skin ulcers between 5-20 cm2 in size that are stable and not infected. Women who are pregnant, breastfeeding, or not using contraception if of childbearing potential cannot join.

Inclusion Criteria

I have been diagnosed with dystrophic epidermolysis bullosa confirmed by specific tests.

I have specific types of skin ulcers due to dystrophic epidermolysis bullosa.

I have two similar skin ulcers, each 5-20 cm2, that haven't changed much in size recently.

Exclusion Criteria

I am not pregnant, breastfeeding, or planning to become pregnant and agree to use contraception during the trial.

I need antibiotics for a bacterial infection in the area of my skin ulcer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ALLO-ASC-SHEET and Vehicle control treatments for target lesions

12 weeks

12 IP applications

Follow-up

Participants are monitored for safety and effectiveness after treatment

25 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ALLO-ASC-SHEET
• Vehicle Control

Trial Overview The study involves applying a new treatment called ALLO-ASC-SHEET to three skin lesions and a placebo (Vehicle control) to one lesion on the same person. The assignment of treatments to each lesion is decided randomly at enrollment.

How Is the Trial Designed?

Group I: ALLO-ASC-SHEET Experimental Treatment 1 Intervention

Allogeneic mesenchymal stem cells Dressing for Dystrophic Epidermolysis Bullosa wound

Group II: Conventional Therapy Active Control 1 Intervention

Hydrogel Sheet Matching control

Who Is Running the Clinical Trial?

Anterogen Co., Ltd.

Lead Sponsor

Trials

31

Recruited

980+

Published Research Related to This Trial

Adipose-derived stem cells (ASC) can be effectively transdifferentiated into keratinocyte-like cells under specific in vitro conditions, particularly using a medium with retinoic acid, hydrocortisone, ascorbic acid, and BMP-4, which enhances their expression of pan-cytokeratin.

The study found that adhesion to type IV collagen and the use of 3D cultures lifted to an air-liquid interface significantly promoted epidermal stratification and the expression of key epidermal differentiation markers, suggesting potential applications in treating non-healing wounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Directing adipose-derived stem cells into keratinocyte-like cells: impact of medium composition and culture condition. Petry, L., Kippenberger, S., Meissner, M., et al.[2019]

Adipose-derived stem cells (ADSCs) and their secretory factors significantly promote hair growth by increasing the proliferation of human follicular cells and protecting dermal papilla cells from damage.

In animal studies, conditioned media from ADSCs not only induced the hair growth phase (anagen) but also enhanced hair shaft elongation, suggesting that ADSC-derived proteins could be effective treatments for hair loss in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Basic Mechanism of Hair Growth Stimulation by Adipose-derived Stem Cells and Their Secretory Factors. Won, CH., Park, GH., Wu, X., et al.[2022]

Topical treatment with adipose-derived stem cells (ADSC) significantly improved corneal wound healing in injured rat corneas, showing smaller epithelial defects compared to control and adipose-treated eyes.

Histological analysis revealed that ADSC-treated corneas achieved complete re-epithelization with reduced inflammation and fibroblast activation, indicating a beneficial effect on corneal repair mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human adipose-derived stem cells for the treatment of chemically burned rat cornea: preliminary results. Zeppieri, M., Salvetat, ML., Beltrami, AP., et al.[2013]

Adipose-derived stromal/stem cells (ASCs) significantly enhance long-term survival of skin allografts in a mouse model, demonstrating their potential to improve outcomes in reconstructive transplantation.

The study showed that co-infusion of ASCs with donor bone marrow cells led to stable immune tolerance and reduced complications associated with traditional long-term immunosuppression, suggesting a promising new approach for treating combat-related injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adipose-derived stromal cells promote allograft tolerance induction. Davis, TA., Anam, K., Lazdun, Y., et al.[2018]

Autologous adipose-derived stem cells (ASCs) from diabetic mice (DMA) demonstrated comparable effectiveness to nondiabetic ASCs in promoting wound healing, improving angiogenesis, and enhancing tissue regeneration in diabetic wounds, based on a study involving 36 db/db mice.

Despite some limitations in osteogenesis, DMAs showed similar capabilities in adipogenesis and overall therapeutic potential, suggesting that using a patient's own stem cells could be a viable treatment option for diabetic wounds without the risks associated with donor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Diabetic Adipose-derived Stem Cells are Comparable to Allogeneic Non-diabetic Counterparts in Improving Diabetic Wound Healing. Chen, B., Wei, Y., Cai, J., et al.[2023]

In a phase II clinical trial involving 59 patients with complex perianal fistulas, treatment with adipose-derived stem cells (ASCs) combined with fibrin glue resulted in a significantly higher healing rate (71%) compared to fibrin glue alone (16%), indicating that ASCs enhance treatment efficacy.

The treatment was well tolerated, with a low recurrence rate of 17.6% at one year, and patients receiving ASCs reported better quality of life scores, suggesting that this therapy is both effective and safe for managing complex perianal fistulas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Garcia-Olmo, D., Herreros, D., Pascual, I., et al.[2022]

Adipose-derived stem cells (ASCs) enhance the proliferation and wound healing capabilities of keratinocytes and dermal fibroblasts, suggesting their potential role in skin repair.

The study found that ASC-conditioned medium (ASC-CM) not only promotes cell growth but also increases collagen production in fibroblasts, indicating that ASCs may aid in chronic wound healing through paracrine signaling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paracrine effects of adipose-derived stem cells on keratinocytes and dermal fibroblasts. Lee, SH., Jin, SY., Song, JS., et al.[2021]

Adipogenic differentiated adipose-derived stem cells (ASCs) can be safely used for allogenic applications, as they do not trigger an immune response in MHC-mismatched recipients, making them a potential 'universal donor' for soft-tissue regeneration.

In a phase I clinical study, these cells did not cause significant local or systemic immune responses or adverse events, indicating their safety for use in donor-independent healthy subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical implication of allogenic implantation of adipogenic differentiated adipose-derived stem cells. Kim, I., Bang, SI., Lee, SK., et al.[2021]

Adipose-derived stromal/stem cells (ASC) can differentiate into epithelial cells when treated with a combination of all-trans retinoic acid (ATRA), Activin A (ActA), and bone morphogenetic protein-7 (BMP-7), indicating their potential for tissue repair.

The combination of these factors not only induced the expression of epithelial markers CK18 and ZO-1 but did so without increasing cell proliferation, suggesting a targeted approach to enhance differentiation without affecting cell growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

During epithelial differentiation of human adipose-derived stromal/stem cells, expression of zonula occludens protein-1 is induced by a combination of retinoic acid, activin-A and bone morphogenetic protein-7. Griesche, N., Bereiter-Hahn, J., Geiger, H., et al.[2018]

In a study involving 30 patients with chronic wounds, transplantation of autologous adipose-derived stem cell (ADSC) sheets significantly improved wound healing, with 90% re-epithelialization observed by three weeks post-treatment.

The treatment led to increased proliferation of key healing components such as fibroblasts and collagen, resulting in reduced wound size and improved wound bed conditions, demonstrating the efficacy of ADSCs in chronic wound management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Adipose-Derived Stem Cell (Adsc) Transplantation In The Management Of Chronic Wounds. Dung, TN., Han, VD., Tien, GN., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02579369

Study to Evaluate the Safety of ALLO-ASC-DFU in ... ALLO-ASC-DFU is a hydrogel sheet containing allogenic adipose-derived mesenchymal stem cells. Adipose-derived stem cells have anti-inflammatory effect and ...

2. withpower.com withpower.com/trial/phase-2-epidermolysis-bullosa-dystrophica-2022-1abb1

ALLO-ASC-SHEET for Epidermolysis Bullosa ALLO-ASC-SHEET uses adipose-derived stem cells, which are unique because they can transform into different types of cells and help repair damaged skin. This ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7985058/

Current Advanced Therapies Based on Human ... In this review, a total of thirteen types of hMSCs used as advanced therapy have been analyzed, considering the last 5 years (2015–2020).

4. sciencedirect.com sciencedirect.com/science/article/pii/S146532492200771X

Adipose-derived stem cells applied in skin diseases ... In this narrative review, the authors give an overview of some of the latest studies concerning wound healing as well as treatment of several skin diseases.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8663784/

Clinical trial of ABCB5+ mesenchymal stem cells for ... Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating, and life-threatening inherited skin fragility disorder. RDEB is caused by biallelic ...

6. trial.medpath.com trial.medpath.com/clinical-trial/289a0645e137fb52/clinical-study-efficacy-safety-alloscdf-diabetic-foot-ulcers

Clinical Study to Evaluate Efficacy and Safety of ALLO-ASC ... ALLO-ASC-DFU is a hydrogel sheet containing allogenic adipose-derived mesenchymal stem cells. Adipose-derived stem cells have anti-inflammatory effect and ...