Stem Cell Therapy for Epidermolysis Bullosa

Overseen By Cristina Daniele

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: RHEACELL GmbH & Co. KG

Disqualifiers: Tumor diseases, Allergies, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

74 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new stem cell therapy called allo-APZ2-OTS for individuals with recessive dystrophic epidermolysis bullosa (RDEB), a rare skin disorder that causes painful, easily blistered skin. The trial aims to determine the safety and effectiveness of this treatment by comparing it to a placebo. Individuals with RDEB who have a persistent, non-infected wound may be suitable candidates for this study. As a Phase 3 trial, this treatment represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking therapy.

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 are currently or have recently been in another clinical trial, you may not be eligible to participate.

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

Research has shown that allo-APZ2-OTS, a type of stem cell treatment, was tested in earlier studies with patients who have recessive dystrophic epidermolysis bullosa (RDEB). These studies assessed the treatment's safety and potential benefits. Reports indicate that most patients tolerated the treatment well. Some experienced mild side effects, but no serious issues were directly linked to the treatment.

The treatment is now undergoing testing in a later phase of clinical trials. This indicates that earlier studies found it relatively safe, but further research is necessary to confirm its long-term safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Epidermolysis Bullosa, which focus on symptom management and wound care, allo-APZ2-OTS is a stem cell therapy that aims to address the root cause of the condition. Researchers are excited about allo-APZ2-OTS because it involves using allogeneic stem cells, which have the potential to regenerate healthy skin and promote healing at a cellular level. This approach could provide a more lasting solution compared to existing treatments, which primarily offer temporary relief.

What evidence suggests that allo-APZ2-OTS might be an effective treatment for recessive dystrophic epidermolysis bullosa?

Research shows that allo-APZ2-OTS, which uses special stem cells called ABCB5+ mesenchymal stem cells (capable of transforming into different tissue types), may help treat recessive dystrophic epidermolysis bullosa (RDEB). Studies have found that these stem cells can reduce skin problems by interacting with the body's immune system. Participants in this trial may receive this treatment, which has demonstrated improvement in patients with a noticeable decrease in RDEB-related skin issues. The treatment is also safe and well-tolerated. Overall, this therapy offers hope as a new way to manage the disease for those with RDEB. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for males and females from 6 months old with confirmed recessive dystrophic epidermolysis bullosa (RDEB). Participants must have a specific wound type, be in good general health, and understand the study. Women who can have children need a negative pregnancy test and agree to use birth control.

Inclusion Criteria

I have RDEB confirmed by genetic testing or skin biopsy.

Subject is eligible to participate in this clinical trial based on general health condition

My wound is between 5-50 cm2, older than 21 days but less than 9 months, and not infected.

Exclusion Criteria

Clinically significant or unstable concurrent disease or other clinical contraindications like an uncontrolled or poorly controlled mental health condition of the subject and/or his/her legal representative that could impact on patient's safety or interfere with study compliance such as inability to attend scheduled study visits

Employees of the sponsor, or employees or relatives of the investigator

Previous participation in this clinical trial (except for screening failures)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous administration of allo-APZ2-OTS or placebo

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• allo-APZ2-OTS
• Placebo

Trial Overview The trial tests allo-APZ2-OTS, an intravenous treatment for RDEB against a placebo. The goal is to see if it's safe and works better than not receiving the active treatment.

How Is the Trial Designed?

Group I: Verum Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

RHEACELL GmbH & Co. KG

Lead Sponsor

Trials

11

Recruited

680+

Published Research Related to This Trial

Bone marrow contains specific cells that can help heal skin wounds and correct defects in the skin's structure, particularly in conditions like epidermolysis bullosa (EB), a genetic skin disease.

Research indicates that the beneficial epithelial progenitors for skin repair come from a specific type of bone marrow stem cell, known as PDGFRalpha-positive mesenchymal stem cells, highlighting their potential for therapeutic use in treating EB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stem cell therapy for intractable skin diseases]. Tamai, K.[2012]

In a phase I/IIa clinical trial involving 16 patients with recessive dystrophic epidermolysis bullosa (RDEB), treatment with ABCB5+ mesenchymal stem cells (MSCs) showed a statistically significant reduction in disease activity scores, indicating potential efficacy as a disease-modifying therapy.

The treatment was well-tolerated, with only three adverse events related to the cell product, all of which were manageable and resolved without lasting effects, suggesting a favorable safety profile for ABCB5+ MSCs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial of ABCB5+ mesenchymal stem cells for recessive dystrophic epidermolysis bullosa. Kiritsi, D., Dieter, K., Niebergall-Roth, E., et al.[2022]

In a clinical trial involving 16 patients with recessive dystrophic epidermolysis bullosa (RDEB), treatment with ABCB5+ mesenchymal stromal cells led to a significant closure of 64.9% of wounds by week 12, with many wounds closing as early as day 17 or 35.

The treatment not only facilitated wound closure but also significantly reduced the rate of new wound formation by 79.3%, suggesting a promising therapeutic efficacy for ABCB5+ MSCs in managing RDEB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ABCB5+ mesenchymal stromal cells facilitate complete and durable wound closure in recessive dystrophic epidermolysis bullosa. Dieter, K., Niebergall-Roth, E., Daniele, C., et al.[2023]

The phase I/IIa trial involving 6 patients with recessive dystrophic epidermolysis bullosa (RDEB) demonstrated that intravenous infusions of allogeneic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) were safe and well tolerated, with no serious adverse events reported.

Patients showed significant improvements in disease severity, blister counts, pain, and quality of life, with the most notable effects observed 56-112 days post-treatment, indicating potential clinical efficacy of hUCB-MSCs in managing RDEB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous allogeneic umbilical cord blood-derived mesenchymal stem cell therapy in recessive dystrophic epidermolysis bullosa patients. Lee, SE., Lee, SJ., Kim, SE., et al.[2021]

ABCB5+ mesenchymal stem cells (MSCs) from discarded skin samples show strong potential for treating chronic skin wounds and inflammatory diseases, demonstrating effective immunomodulatory and wound healing properties.

The FDA has approved a phase III trial for ABCB5+ MSCs in treating recessive dystrophic epidermolysis bullosa, and they are now accessible for treating chronic venous ulcers in Germany, highlighting their promising therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skin-Derived ABCB5+ Mesenchymal Stem Cells for High-Medical-Need Inflammatory Diseases: From Discovery to Entering Clinical Routine. Niebergall-Roth, E., Frank, NY., Ganss, C., et al.[2023]

ABCB5+ dermal mesenchymal stem cells (DSCs) show superior ability to migrate and engraft in skin wounds compared to bone marrow-derived MSCs, suggesting they may be more effective for treating skin conditions like recessive dystrophic epidermolysis bullosa (RDEB).

The unique expression of HOXA3 in ABCB5+ DSCs may enhance their skin homing properties, which could lead to improved wound healing and has potential implications for broader regenerative medicine applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ABCB5+ dermal mesenchymal stromal cells with favorable skin homing and local immunomodulation for recessive dystrophic epidermolysis bullosa treatment. Riedl, J., Pickett-Leonard, M., Eide, C., et al.[2022]

The use of allogeneic adipose-derived mesenchymal stem cells (ADMSC) in a patient with recessive dystrophic epidermolysis bullosa (RDEB) showed significant long-lasting improvements in wound healing, pain, and quality of life, with effects observed up to 2 years after treatment.

ADMSC treatment was well-tolerated and correlated with changes in immune response and levels of profibrotic factors, suggesting a potential new therapeutic option for patients who do not respond to conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial Effect of Systemic Allogeneic Adipose Derived Mesenchymal Cells on the Clinical, Inflammatory and Immunologic Status of a Patient With Recessive Dystrophic Epidermolysis Bullosa: A Case Report. Maseda, R., Martínez-Santamaría, L., Sacedón, R., et al.[2020]

Citations

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

Clinical trial of ABCB5+ mesenchymal stem cells for ... This trial demonstrates good tolerability, manageable safety, and potential efficacy of i.v. ABCB5+ MSCs as a readily available disease-modifying therapy for ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03529877

NCT03529877 | Allogeneic ABCB5-positive Stem Cells for ... The aim of this clinical trial is to investigate the efficacy (by monitoring overall improvement of EB symptoms) and safety (by monitoring adverse events) ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1465324923000361

ABCB5+ mesenchymal stromal cells facilitate complete ... The beneficial effect of ABCB5+ MSCs on disease severity was mainly attributable to a decrease in skin activity, with patients whose Epidermolysis Bullosa ...

4. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/allogeneic-skin-derived-abcb5-positive-mscs-allo-apz2-ots

allogeneic skin-derived ABCB5-positive MSCs allo-APZ2- ... Upon administration of the allo-APZ2-OTS, the MSCs are able to differentiate into several lineages, provide immunomodulatory activity, interact with various ...

5. clinicaltrials.eu clinicaltrials.eu/inn/allogeneic-skin-derived-abcb5-positive-dermal-mesenchymal-stromal-cells/

Allogeneic Skin-Derived Abcb5-Positive Dermal ... Clinical trials are currently underway to study ABCB5+ MSCs for both Epidermolysis Bullosa and chronic venous ulcers. These trials will help researchers ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05838092?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(Epidermolysis%20bullosa%20OR%20%22acantholysis%20bullosa%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)))&rank=7

Allogeneic ABCB5-positive Dermal Mesenchymal Stromal ... The aim of this clinical trial is to investigate the safety and efficacy of allo-APZ2-OTS administered intravenously to subjects with recessive dystrophic ...

7. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/allogeneic-skin-derived-abcb5-positive-mscs-allo-apz2-ots

Clinical Trials Using Allogeneic Skin-derived ABCB5 ... Review the clinical trials studying allogeneic skin-derived abcb5-positive mscs allo-apz2-ots on this list and use the filters to refine the results by age ...