allo-APZ2-CVU for Venous Leg Ulcers

Recruiting at 16 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

250 Participants Needed

Trial Summary

What is the purpose of this trial?

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 compared to placebo.

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.

What data supports the effectiveness of the treatment allo-APZ2-CVU for Venous Leg Ulcers?

Research shows that skin-derived ABCB5-positive mesenchymal stem cells (a type of cell that can develop into different types of tissues) significantly reduced wound size in patients with chronic venous ulcers, with a median reduction of up to 87% in some cases. This suggests that these cells could be a promising treatment for non-healing venous leg ulcers. ^{1 2 3 4 5}

Is allo-APZ2-CVU safe for humans?

In a clinical trial for chronic venous ulcers, the treatment with ABCB5+ mesenchymal stem cells, which includes allo-APZ2-CVU, was generally safe. Out of 83 adverse events, only three were related to the treatment, and they were mild or moderate and resolved without lasting effects. ^{2 3 5 6 7}

How is the treatment allo-APZ2-CVU different from other treatments for venous leg ulcers?

The treatment allo-APZ2-CVU uses ABCB5-positive mesenchymal stem cells (special cells that can help repair tissues) to reduce inflammation and promote healing in chronic venous leg ulcers that don't respond to standard care. This approach is unique because it targets inflammation at the wound site, helping to shift the immune response from harmful to healing, which is not typically addressed by other treatments. ^{3 4 5 6 8}

Research Team

Anna Moessmer

Principal Investigator

RHEACELL GmbH & Co. KG

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[Preliminary study on autologous bone marrow mononuclear cells transplantation for lower limb chronic venous ulcer]. [2011]

2. England 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. [2015]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Allogeneic ABCB5+ mesenchymal stem cells for treatment-refractory chronic venous ulcers: a phase I/IIa clinical trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Autologous bone marrow-derived cells for venous leg ulcers treatment: a pilot study. [2020]

5. England 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. [2020]

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

Adipose-derived stem cells in patients with venous ulcers: Systematic review. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Role of mesenchymal stromal cells derivatives in diabetic foot ulcers: a controlled randomized phase 1/2 clinical trial. [2023]

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

Open-label Venous Leg Ulcer Pilot Study Using a Novel Autolologous Homologous Skin Construct. [2022]