allo-APZ2-CVU for Venous Leg Ulcers

Not currently recruiting at 15 trial locations

Overseen By Anna Moessmer

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: RHEACELL GmbH & Co. KG

Must not be taking: Immunosuppressives, Cytotoxics, Steroids

Disqualifiers: Diabetes, Peripheral artery disease, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 16

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a topical treatment called allo-APZ2-CVU to determine its effectiveness in healing venous leg ulcers that haven't responded to other therapies. These ulcers often appear on the lower leg or ankle and can be painful and difficult to heal. Participants will receive either the treatment or a placebo for comparison. The trial seeks individuals with a chronic venous leg ulcer that hasn't healed for up to 15 years and measures between 1 and 25 cm². As a Phase 3 trial, this treatment is in the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking medical advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications known to influence wound healing, such as systemic immunosuppressives, cytotoxic drugs, and high-dose systemic steroids. If you're on these medications, you may need to stop them to participate.

Is there any evidence suggesting that allo-APZ2-CVU is likely to be safe for humans?

Research has shown that allo-APZ2-CVU, a stem cell therapy, can help heal chronic wounds by reducing inflammation. This treatment uses special stem cells with unique healing properties.

Studies have generally found these stem cells to be safe for patients, with no significant reports of serious side effects in earlier trials. The treatment is now undergoing advanced trials, indicating that previous trials did not raise major safety concerns.

Overall, evidence suggests that allo-APZ2-CVU is safe for humans, though minor side effects may still occur, as with any treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for venous leg ulcers?

Unlike standard treatments for venous leg ulcers, which often involve compression therapy or topical medications, allo-APZ2-CVU is unique because it uses allogeneic, or donor-derived, stem cells. Researchers are excited about this treatment because these stem cells have the potential to enhance the body’s natural healing processes, potentially leading to faster and more effective ulcer healing. This innovative approach targets the underlying causes of chronic ulcers, offering new hope for patients who have not responded well to current therapies.

What evidence suggests that allo-APZ2-CVU might be an effective treatment for venous leg ulcers?

Research has shown that allo-APZ2-CVU, a treatment using special stem cells, may help heal chronic wounds like venous leg ulcers. These stem cells reduce inflammation, a major issue in wounds that don't heal well. Previous studies demonstrated that these cells improve healing by targeting the inflammation that keeps wounds open. This trial will test allo-APZ2-CVU in one arm, while another arm will receive a placebo. This new approach aims to directly address the persistent inflammation that makes these ulcers hard to treat. Although this therapy is still under investigation, early results are promising for those with difficult-to-treat ulcers. ^{1 2 3 5 6}

Who Is on the Research Team?

Anna Moessmer

Principal Investigator

RHEACELL GmbH & Co. KG

Are You a Good Fit for This Trial?

This trial is for individuals with chronic venous ulcers (CVUs) that haven't healed despite previous treatments. Specific details about who can join or reasons why someone might not be eligible are not provided.

Inclusion Criteria

I am willing to use effective birth control during the trial.

Body mass index between 15 and 50 kg/m²

Patients must be able to understand the nature of the study and provide written informed consent prior to any clinical trial procedures

Exclusion Criteria

Patients who, in the opinion of the investigator, for any reason are unable or unwilling to complete the trial per protocol (e.g. alcohol or substance abuse, not mobile, short life expectancy) or there is evidence of any other medical condition (such as psychiatric illness, physical examination, or laboratory findings) that may interfere with the planned treatment, affect the patient's compliance, or place the patient at high risk of complications related to the treatment

I haven't had any cancer in the past 5 years, except for certain skin cancers that were successfully treated.

I have leg pain from poor circulation that needs treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive allo-APZ2-CVU or placebo topically on Day 0

1 day

1 visit (in-person)

Efficacy Follow-up

Participants are monitored for efficacy of the treatment for 18 weeks

18 weeks

11 visits (in-person)

Safety Follow-up

Three safety follow-up visits to monitor long-term safety

10 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• allo-APZ2-CVU

Trial Overview The trial tests allo-APZ2-CVU, a new treatment applied directly to non-healing CVUs, against a placebo to see if it's more effective and safe in healing these persistent leg ulcers.

How Is the Trial Designed?

Group I: Verum Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

allo-APZ2-CVU is already approved in United States for the following indications:

Approved in United States as allo-APZ2-CVU for:

• None approved yet; currently in Phase III trials for CVU and Epidermolysis Bullosa

Who Is Running the Clinical Trial?

RHEACELL GmbH & Co. KG

Lead Sponsor

Trials

11

Recruited

680+

FGK Clinical Research GmbH

Industry Sponsor

Trials

53

Recruited

6,700+

Published Research Related to This Trial

Local administration of mesenchymal stem cells (MSCs) derived from ABCB5+ dermal cells significantly reduced inflammation and accelerated healing in a mouse model of nonhealing wounds, mimicking human venous leg ulcers.

The healing effects were attributed to the secretion of interleukin-1 receptor antagonist (IL-1RA) by ABCB5+ MSCs, which shifted the balance from proinflammatory M1 macrophages to repair-promoting M2 macrophages, indicating a promising new approach for treating chronic wounds in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Newly Defined ATP-Binding Cassette Subfamily B Member 5 Positive Dermal Mesenchymal Stem Cells Promote Healing of Chronic Iron-Overload Wounds via Secretion of Interleukin-1 Receptor Antagonist. Vander Beken, S., de Vries, JC., Meier-Schiesser, B., et al.[2020]

In a study involving 17 patients with chronic venous ulcers, autologous bone marrow mononuclear cell transplantation significantly accelerated healing, with a median healing time of 22 days compared to 57.5 days in a control group of 10 patients.

The transplantation group showed increased microvessel density in granulation tissue, indicating enhanced blood vessel formation, which likely contributed to the improved healing outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preliminary study on autologous bone marrow mononuclear cells transplantation for lower limb chronic venous ulcer]. Huang, W., Wang, L., Tan, B., et al.[2011]

In a pilot study involving 10 patients with venous leg ulcers (VLUs), the autologous homologous skin construct (AHSC) showed promising results, with 8 out of 10 ulcers achieving complete closure within 12 weeks after a single application.

The mean time to closure was 34 days, and all grafts successfully took, indicating that AHSC could be a viable treatment option for VLUs, although further research in larger studies is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label Venous Leg Ulcer Pilot Study Using a Novel Autolologous Homologous Skin Construct. Armstrong, DG., Orgill, DP., Galiano, RD., et al.[2022]

In a pilot study involving four patients with chronic venous leg ulcers, the use of autologous bone marrow-derived cell (BMDC) therapy alongside standard treatment resulted in significant reductions in ulcer size and wound pain after 12 months (P < 0.05).

The BMDC treatment was found to be safe and well tolerated over the long term, suggesting it could be a promising adjuvant therapy for enhancing healing in chronic wounds, although further research with larger randomized controlled trials is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous bone marrow-derived cells for venous leg ulcers treatment: a pilot study. Otero, G., Agorio, C., Sujanov, A., et al.[2020]

In a phase I/IIa clinical trial involving patients with chronic venous ulcers resistant to standard treatment, topical applications of ABCB5+ mesenchymal stem cells (MSCs) led to a significant median wound size reduction of 76% to 87% over 12 weeks, demonstrating their potential efficacy in healing non-healing wounds.

The treatment was well tolerated, with only three mild to moderate adverse events related to the cell product, indicating a favorable safety profile for ABCB5+ MSCs in the treatment of chronic venous ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic ABCB5+ mesenchymal stem cells for treatment-refractory chronic venous ulcers: a phase I/IIa clinical trial. Kerstan, A., Dieter, K., Niebergall-Roth, E., et al.[2023]

Adipose-derived stem cells (ADSCs) showed promising results in healing venous leg ulcers (VLU), with a 75% healing rate reported in a randomized study compared to 50% in the control group, and one study achieving 100% healing.

The application of ADSCs was associated with a decrease in pain scores and no serious complications, suggesting that this treatment is safe for patients with chronic VLUs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adipose-derived stem cells in patients with venous ulcers: Systematic review. Elsharkawi, M., Ghoneim, B., Westby, D., et al.[2023]

The study demonstrated that HP802-247, a spray-applied cell therapy containing neonatal keratinocytes and fibroblasts, significantly reduced the area of chronic venous leg ulcers compared to a placebo, particularly with the optimal dosing of 0.5×10^6 cells/mL every 14 days.

Adverse events were similar across all treatment groups, indicating that HP802-247 is a safe option for treating venous leg ulcers, with no significant increase in serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spray-applied cell therapy with human allogeneic fibroblasts and keratinocytes for the treatment of chronic venous leg ulcers: a phase 2, multicentre, double-blind, randomised, placebo-controlled trial. Kirsner, RS., Marston, WA., Snyder, RJ., et al.[2015]

In a phase 1/2 clinical trial involving patients with grade 1 and 2 diabetic foot ulcers (DFUs), the administration of allogeneic bone marrow mesenchymal stromal cell derivatives (allo-hBM-MSCDs) was found to be safe, with no reported adverse events.

Patients treated with allo-hBM-MSCDs or allo-hBM-MSCs showed significantly greater wound closure and faster skin regeneration compared to those receiving conventional treatment with PolyMem dressing, indicating a promising new approach for managing DFUs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of mesenchymal stromal cells derivatives in diabetic foot ulcers: a controlled randomized phase 1/2 clinical trial. Arango-Rodríguez, ML., Solarte-David, VA., Becerra-Bayona, SM., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06489028

Study Details | NCT06489028 | Allogeneic ABCB5-positive ... The aim of this clinical trial is to investigate the efficacy and safety of allo-APZ2-CVU, administered topically on therapy-resistant non-healing CVUs ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8635035/

Allogeneic ABCB5+ Mesenchymal Stem Cells for ... Skin-derived ABCB5+ mesenchymal stem cells can dampen the sustained IL-1β‒driven inflammation present in chronic wounds. On the basis of their wound healing‒ ...

3. rheacell.com rheacell.com/pdf/20240924_ots_Fachmeldung_RHEACELL_CVU_Phase_3_Genehmigung_EN_final.pdf

RHEACELL announces FDA approval for Phase 3 study in ... Allo-APZ2-CVU is a first-in-class stem cell therapy leveraging. ABCB5-positive mesenchymal stem cells (MSCs) to treat patients with severe.

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

ABCB5+ mesenchymal stromal cells facilitate complete ... Recessive dystrophic epidermolysis bullosa (RDEB) is a hereditary, rare, devastating and life-threatening skin fragility disorder with a high unmet medical ...

5. go.drugbank.com go.drugbank.com/drugs/DB17862

Skin-derived ABCB5-positive Mesenchymal Stem cells Skin-derived ABCB5-positive Mesenchymal Stem cells are under investigation in clinical trial NCT04971161 (Allogeneic Abcb5-positive Dermal ...

6. biorn.org biorn.org/rheacell-receives-ema-approval-for-allo-apz2-cvu-phase-3-trial-in-chronic-venous-ulcers/

RHEACELL receives EMA approval for allo-APZ2-CVU ... allo-APZ2-CVU leverages ABCB5-positive mesenchymal stem cells with unique immunomodulatory properties to treat patients with severe immune ...