ALLO-ASC-SHEET for Diabetic Foot Ulcer

Overseen By Yun Jung Choi, PM

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Anterogen Co., Ltd.

Must not be taking: Antibiotics, Corticosteroids, Immunosuppressives, others

Disqualifiers: HIV, Hepatic deficiencies, Renal insufficiency, others

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: Unknown

Duration: 12 weeks

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 diabetic foot ulcers. The goal is to determine if this hydrogel sheet, containing special cells from fat tissue (adipose-derived stem cells), can heal these ulcers more effectively and safely than a similar sheet without the cells. Individuals with Type I or Type II diabetes and a specific type of foot ulcer (Wagner Grade II) present for more than four weeks are likely suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on high-dose antibiotics, certain steroids, or immunosuppressive drugs. It's best to discuss your current medications with the study team.

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

Research has shown that ALLO-ASC-SHEET, a special gel-like sheet made with donor stem cells, has been safe in earlier studies. These stem cells can reduce inflammation, lowering swelling and supporting healing. In studies involving people with diabetic foot ulcers, the treatment was well-received, and no major safety issues emerged. While minor side effects can occur with most treatments, no serious problems related to the gel have been reported. This suggests that ALLO-ASC-SHEET is generally safe for people based on current research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for diabetic foot ulcers?

ALLO-ASC-SHEET is unique because it uses allogenic adipose-derived mesenchymal stem cells embedded in a hydrogel sheet to treat diabetic foot ulcers. Unlike standard treatments that focus primarily on wound care and infection control, this treatment aims to harness the regenerative potential of stem cells to promote healing. Researchers are excited about this approach because it could potentially accelerate the healing process and improve outcomes for patients with chronic wounds, offering a novel mechanism of action that targets the underlying issues of tissue repair and regeneration.

What evidence suggests that ALLO-ASC-SHEET might be an effective treatment for diabetic foot ulcers?

Research has shown that ALLO-ASC-SHEET, which contains special cells from fat tissue that aid in wound healing, may effectively treat diabetic foot ulcers. These cells, known as adipose-derived mesenchymal stem cells, improve wound healing by reducing swelling and aiding tissue repair. In this trial, participants will receive either the ALLO-ASC-SHEET or a vehicle control hydrogel sheet without these stem cells. Past studies have demonstrated that patients using treatments with similar stem cells healed better than those who did not. This suggests that ALLO-ASC-SHEET could help close and heal foot ulcers in people with diabetes. Overall, the early findings are promising, indicating better outcomes for wound healing with this treatment. ^{1 3 5 6 7}

Who Is on the Research Team?

Yun Jung Choi, PM

Principal Investigator

Anterogen Co., Ltd.

Are You a Good Fit for This Trial?

Adults aged 18-80 with Type I or II diabetes and a Wagner Grade II foot ulcer between 1.5 cm2 and 15 cm2 that hasn't reached the bone, is free of dead tissue and infection, has good blood flow around it, and has been present for over 4 weeks. Excludes those with certain immune responses, non-diabetic ulcers, severe infections or liver/kidney issues, high HbA1c levels (>10%), allergies to specific proteins or glues, recent other treatments or trials participation.

Inclusion Criteria

The blood circulation around the ulcer meets one of the following criteria: A. Blood flow around the ulcer is checked using Doppler Test and shows specific patterns. B. The range of Ankle Brachial Index (ABI) is within a certain range. C. The transcutaneous oxygen pressure (TcPO2) is above a certain level.

I have a grade II ulcer that affects muscle or tendon but not bone.

My ulcer is clean and shows no signs of infection.

Exclusion Criteria

Is considered by the Investigator to have a significant disease which might impact the study

I have had cancer other than basal cell carcinoma in the last 5 years.

I cannot avoid putting weight on a certain part of my body.

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 or placebo for diabetic foot ulcers

12 weeks

Regular visits for wound assessment

Follow-up

Participants are monitored for durability of complete wound closure

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ALLO-ASC-SHEET

Trial Overview This phase 2 trial tests ALLO-ASC-SHEET's effectiveness in healing diabetic foot ulcers compared to a placebo. It's double-blind meaning neither participants nor researchers know who gets the real treatment versus placebo during the study.

How Is the Trial Designed?

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

ALLO-ASC-SHEET Hydrogel sheet containing allogenic adipose-derived mesenchymal stem cells

Group II: Hydrogel SHEET(Vehicle control) Placebo Group 1 Intervention

Vehicle Control Hydrogel sheet without allogenic adipose-derived mesenchymal stem cells

Who Is Running the Clinical Trial?

Anterogen Co., Ltd.

Lead Sponsor

Trials

31

Recruited

980+

Published Research Related to This Trial

Transplanting allogeneic adipose-derived stem cell (ASC) sheets into diabetic rats with full-thickness skin defects significantly accelerated wound healing and improved blood vessel formation within 2 weeks, indicating their potential effectiveness for treating nonhealing diabetic ulcers.

The ASC sheets not only promoted healing directly but also enhanced the formation of new blood vessels by secreting angiogenic growth factors, suggesting a dual mechanism of action in improving wound recovery in diabetic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic Transplantation of an Adipose-Derived Stem Cell Sheet Combined With Artificial Skin Accelerates Wound Healing in a Rat Wound Model of Type 2 Diabetes and Obesity. Kato, Y., Iwata, T., Morikawa, S., et al.[2022]

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 study involving 59 patients with diabetic foot ulcers, treatment with allogeneic adipose-derived stem cell (ASC) sheets resulted in a significantly higher rate of complete wound closure compared to a control group using polyurethane film, achieving 82% closure by week 12 versus 53%.

The treatment with ASC sheets was found to be safe, with no serious adverse events reported, suggesting that allogeneic ASCs could be a promising option for effectively treating diabetic foot ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of Allogeneic Adipose-Derived Stem Cell-Hydrogel Complex for Treating Diabetic Foot Ulcers. Moon, KC., Suh, HS., Kim, KB., et al.[2019]

In a study involving 16 patients with diabetic foot ulcers (DFUs) that had not healed with standard treatments, the use of autologous skin cell suspension (ASCS) combined with standard therapy resulted in a significant average reepithelialization of 84.9% and a reduction in ulcer area by 12.2 cm² over 26 weeks.

All ulcers showed positive healing trajectories, with those free from soft tissue infections achieving either complete healing or at least 95% reepithelialization, indicating that ASCS is a promising and well-tolerated treatment option for DFUs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot feasibility study of non-cultured autologous skin cell suspension for healing diabetic foot ulcers. Rashid, ST., Cavale, N., Bowling, FL.[2021]

A review of 11 randomized controlled trials found that adding allogeneic skin substitutes and human placental membrane allografts to standard wound care significantly increases the healing rates of diabetic foot ulcers (DFUs) at 6 and 12 weeks.

One study suggested that placental membrane allografts may be more effective than allogeneic skin substitutes, but more research is needed to confirm this finding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic Skin Substitutes Versus Human Placental Membrane Products in the Management of Diabetic Foot Ulcers: A Narrative Comparative Evaluation of the Literature. Luck, J., Rodi, T., Geierlehner, A., et al.[2019]

A 57-year-old woman with a 20-day diabetic foot ulcer (DFU) showed significant healing after treatment with placenta-derived mesenchymal stem cells (PDMSCs) hydrogel, indicating its potential efficacy in wound repair.

The treatment was safe, with no complications or recurrence of the ulcer observed over a 6-month follow-up period, suggesting that PDMSCs hydrogel could be a promising new approach for managing DFUs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-week topical treatment with placenta-derived mesenchymal stem cells hydrogel in a patient with diabetic foot ulcer: A case report. Zeng, X., Tang, Y., Hu, K., et al.[2022]

Mesenchymal stem cells (MSCs) have shown promise in treating diabetic foot ulcers (DFU) by accelerating wound healing and improving clinical outcomes, potentially reducing the need for amputations.

Bone marrow-derived MSCs (BM-MSCs) are highlighted as a particularly effective and cost-efficient option for transplantation in DFU treatment, offering a safe alternative with no ethical concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer. Cao, Y., Gang, X., Sun, C., et al.[2022]

Exosomes from mmu_circ_0001052-modified adipose-derived stem cells (ADSCs) significantly enhance wound healing in diabetic foot ulcers (DFU) by promoting angiogenesis through the miR-106a-5p and FGF4/p38MAPK pathway.

The study demonstrated that these exosomes reduce apoptosis and increase proliferation and migration of high glucose-induced human umbilical vein endothelial cells (HUVECs), indicating their potential as a therapeutic intervention for DFU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exosomes from mmu_circ_0001052-modified adipose-derived stem cells promote angiogenesis of DFU via miR-106a-5p and FGF4/p38MAPK pathway. Liang, ZH., Pan, NF., Lin, SS., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02619877

Clinical Study to Evaluate Efficacy and Safety of ALLO-ASC ... This is a phase II single-blinded study to evaluate the efficacy and safety of ALLO-ASC-DFU in patients with Diabetic Foot Ulcer, compared to standard therapy.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36674989/

Allogenic Adipose-Derived Stem Cells in Diabetic Foot ... This work aimed to examine the safety and efficacy of allogenic ADSCs in human diabetic foot ulcer treatment, in combination with the analyses of the wound.

3. diabetesjournals.org diabetesjournals.org/diabetes/article/68/4/837/39767/Potential-of-Allogeneic-Adipose-Derived-Stem-Cell

Potential of Allogeneic Adipose-Derived Stem Cell–Hydrogel ... The purpose of this study was to examine the potential of allogeneic ASC sheets for treating diabetic foot ulcers.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04497805

NCT04497805 | Clinical Study of ALLO-ASC-SHEET in ... This is a phase 2 double-blind clinical study to evaluate the efficacy and Safety of ALLO-ASC-SHEET in subjects with Diabetic Wagner Grade II Foot Ulcers, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11229965/

Adipose-derived stem cells in diabetic foot care Adipose-derived stem cells (ADSCs) have been identified as a promising therapeutic approach for improving wound healing in DFUs.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02394886

Safety of ALLO-ASC-DFU in the Patients With Diabetic Foot ... ALLO-ASC-DFU is a hydrogel sheet containing allogenic adipose-derived mesenchymal stem cells. Adipose-derived stem cells have anti-inflammatory effect and ...

7. 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).