Amnion Membrane Allograft for Venous Leg Ulcers

Overseen By Melissa Crosswhite

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Skye Biologics Holdings, LLC

Must not be taking: Immunosuppressants, Chemotherapy, Steroids

Disqualifiers: Infection, Osteomyelitis, Diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, E-GRAFT™ (an amnion membrane allograft) and FIBRACOL™, to determine which more effectively heals venous leg ulcers. Researchers will assess the speed of ulcer closure, changes in size over 12 weeks, side effects, pain levels, and infections. Participants should have had a leg or foot ulcer for at least four weeks that hasn't healed with standard care and must agree to weekly study visits. As an unphased trial, this study provides participants the chance to contribute to valuable research that could enhance future treatment options for venous leg ulcers.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressants or high doses of corticosteroids, you may be excluded from participating.

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

Research has shown that amnion membrane allografts, such as E-GRAFT™, are generally safe for people. These allografts, derived from the amniotic sac, have been used safely to treat wounds like diabetic foot ulcers and venous leg ulcers. In these studies, patients tolerated the treatments well, with few reports of serious side effects. This suggests that E-GRAFT™ is likely safe for most people when included in a wound care plan. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

E-GRAFT™ is unique because it utilizes an amnion membrane allograft to aid in the healing of venous leg ulcers. Unlike traditional treatments like compression therapy or dressings that focus on managing symptoms and promoting moisture balance, E-GRAFT™ leverages the regenerative properties of the amnion membrane, which is rich in growth factors and anti-inflammatory proteins. This innovative approach aims to accelerate healing by actively promoting tissue regeneration, making it a promising option for those with chronic wounds.

What evidence suggests that this trial's treatments could be effective for venous leg ulcers?

Studies have shown that amnion membrane allografts, such as E-GRAFT™, effectively treat venous leg ulcers. Research indicates that these grafts promote wound healing by encouraging new tissue growth and reducing swelling. Initial findings suggest that E-GRAFT™, which participants in this trial may receive, closes wounds more effectively than some other treatments. The success of these support structures for cells in healing chronic leg ulcers highlights the potential benefits of E-GRAFT™. This trial will compare E-GRAFT™ with FIBRACOL™, another treatment option in the study, to evaluate their effectiveness in healing ulcers regardless of initial size. ^{1 6 7 8 9}

Who Is on the Research Team?

Charles M Zelen, DPM FACFAS

Principal Investigator

Professional Education and Research Institute

Are You a Good Fit for This Trial?

This trial is for individuals with non-healing venous leg ulcers. Participants should have a wound that hasn't improved with standard treatments. Specific details about who can join or reasons someone might be excluded are not provided here.

Inclusion Criteria

The subject must be willing and able to participate in the informed consent process

The subject must agree to attend the weekly study visits required by the protocol

My ulcer has been treated with compression therapy for at least 2 weeks.

Exclusion Criteria

A subject known to have a life expectancy of less than 6 months is excluded

I am not on high-dose steroids or chemotherapy that weakens my immune system.

I have not had a partial leg amputation that affects wound healing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either E-GRAFT™ or FIBRACOL™ as the primary dressing along with standard of care for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• E-GRAFT™
• FIBRACOL™

Trial Overview The study compares two treatments: E-GRAFT™ combined with Standard Of Care (SOC) versus FIBRACOL™ also combined with SOC, to see which is better at healing venous leg ulcers over a period of 12 weeks.

How Is the Trial Designed?

Group I: SOC primary dressing with E-GRAFT ™ Experimental Treatment 1 Intervention

Participants receive standard of care with E-GRAFT™

Group II: SOC primary dressing with FIBRACOL™ Active Control 1 Intervention

Participants receive standard of care with FIBRACOL™

Who Is Running the Clinical Trial?

Skye Biologics Holdings, LLC

Lead Sponsor

Trials

4

Recruited

540+

Published Research Related to This Trial

In a pilot study involving 13 patients with chronic varicose leg ulcers that did not respond to standard treatments, the use of amniotic membrane (AM) showed effectiveness in promoting healing and epithelization.

After 2 years, only 23% of the patients experienced a recurrence of their ulcers, suggesting that AM can be a viable treatment option for patients with refractory ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic Membrane in the Treatment of Varicose Ulcers: a Center Experience. Rocha-Neves, J., Ferreria, A., Sousa, J., et al.[2019]

A fresh human placental membrane allograft was successfully used to heal a chronic venous ulcer in an 89-year-old woman, demonstrating its potential effectiveness in treating long-standing wounds.

After 60 days of treatment, the ulcer was completely healed, indicating that the amniochorionic membrane can be a viable therapeutic option for chronic vascular ulcers that do not respond to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Healing of a chronic ulcer of the lower limb of venous origin with fresh human amniochorionic membrane allograft Piamo, A., García, M., Romero, D., et al.[2023]

Amniotic membrane grafting shows promise for promoting healing in venous ulcers, particularly when autografts are not suitable, but it remains classified as an experimental therapy due to limited safety and efficacy studies.

While autografts are the least expensive option for treatment, amniotic membrane grafts could be more cost-effective than biocompatible skin substitutes over time, potentially saving €6765 at 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cost-benefit analysis of amniotic membrane transplantation for venous ulcers of the legs that are refractory to conventional treatment]. Gutiérrez-Moreno, S., Alsina-Gibert, M., Sampietro-Colom, L., et al.[2018]

In a pilot study involving 15 patients with chronic venous leg ulcers, amniotic membrane (AM) grafts demonstrated a 100% engraftment rate and significantly improved healing, with granulation tissue increasing from 17% to 69% over 14 days.

AM transplantation was found to be safe, with no adverse events reported, and resulted in a significant reduction in ulcer-related pain, making it a promising low-cost alternative for treating chronic leg ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of amniotic membrane transplantation in the treatment of venous leg ulcers. Mermet, I., Pottier, N., Sainthillier, JM., et al.[2022]

Amniotic membrane transplantation showed promising results in treating refractory chronic leg ulcers, with complete re-epithelialization achieved in one case by week 8 and an average wound size reduction of 81.93% by week 16 across four ulcers.

The treatment also significantly reduced pain intensity by 86.6% without any observed adverse effects, suggesting it is a safe and effective alternative for patients with difficult-to-treat ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic membrane transplantation in the treatment of chronic lower limb ulcers. Alsina-Gibert, M., Pedregosa-Fauste, S.[2012]

Human amniotic membrane has been shown to positively affect chronic venous leg ulcers by promoting healing processes such as granulation tissue formation and re-epithelialization.

Despite its benefits, more randomized clinical studies are necessary to fully establish its efficacy and optimize its use in wound healing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Human amniotic membrane in the management of chronic venous leg ulcers]. Tauzin, H., Humbert, P., Viennet, C., et al.[2022]

In a randomized controlled trial involving 60 patients with chronic venous leg ulcers, the use of dehydrated human amnion and chorion allograft (dHACA) combined with standard care resulted in a significantly higher healing rate (75%) compared to standard care alone (30%) after 12 weeks.

The treatment was found to be safe, with a 63.5% adverse event rate, but none of the adverse events were related to the graft or procedure, indicating that dHACA is a beneficial and safe option for treating chronic venous leg ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter, Randomized, Controlled, Clinical Trial Evaluating Dehydrated Human Amniotic Membrane in the Treatment of Venous Leg Ulcers. Serena, TE., Orgill, DP., Armstrong, DG., et al.[2023]

In a study involving 84 participants, the use of dehydrated human amnion/chorion membrane allograft combined with multilayer compression therapy resulted in 62% of patients achieving over 40% wound closure at 4 weeks, compared to only 32% in the control group, indicating significant efficacy of the allograft treatment (p = 0.005).

Wounds treated with the allograft showed a mean size reduction of 48.1% after 4 weeks, compared to just 19.0% for those receiving multilayer compression therapy alone, highlighting the allograft's potential to enhance healing in venous leg ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, randomized, controlled clinical trial evaluating the use of dehydrated human amnion/chorion membrane allografts and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers. Serena, TE., Carter, MJ., Le, LT., et al.[2022]

The human acellular amniotic membrane (HAAM) was found to be effective in treating venous lower limb ulcers, with complete healing in 2 out of 4 patients and significant reductions in ulcer size and depth in all cases.

HAAM treatment not only led to improved healing outcomes, such as >50% granulation tissue formation and the disappearance of infection signs, but it also proved to be more cost-effective compared to traditional treatments like skin autografts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human acellular amniotic membrane is adopted to treat venous ulcers. Wu, Z., Liu, X., Yuan, D., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8052075/

Effectiveness of different types of skin grafting for treating ... This protocol will use Bayesian NMA to assess the effectiveness of different types of skin grafting for treating venous leg ulcers.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06764953

Clinical Trial Evaluating an Amnion Membrane Allograft ... The main purpose of this research study is to compare the proportion of wound closure in subjects that receive E-GRAFT™ with SOC versus FIBRACOL™ with SOC.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0741521405001813

Effectiveness of an extracellular matrix graft (OASIS Wound ... These data suggest that the SIS wound matrix is effective in healing chronic leg ulcers regardless of the baseline ulcer size. Débridement is also known to be ...

4. journals.lww.com journals.lww.com/md-journal/fulltext/2021/04160/effectiveness_of_different_types_of_skin_grafting.88.aspx

Effectiveness of different types of skin grafting for... : Medicine Results: This protocol will use Bayesian NMA to assess the effectiveness of different types of skin grafting for treating venous leg ulcers.

5. jvsvenous.org jvsvenous.org/article/S2213-333X(21)00305-X/fulltext

Review of the current evidence for topical treatment ... In the present review, we focused on describing the rationale and scientific basis for topical wound care in the management of VLUs.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9586828/

A Multicenter, Randomized, Controlled, Clinical Trial ... In particular, dehydrated and cryopreserved human amnion/chorion allografts have been shown to be safe and effective in randomized controlled trials evaluating ...

7. cms.gov cms.gov/medicare-coverage-database/view/lcd.aspx?lcdid=39864&ver=2

Skin Substitute Grafts/Cellular and Tissue-Based Products ... This LCD covers skin substitute grafts/cellular and tissue-based products (CTP) for the treatment of diabetic foot ulcers (DFU) and venous leg ulcers (VLU) in ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/hsr2.70819

A Multicenter, Randomized, Controlled, Clinical Trial ... This multicenter, randomized, controlled study provides Level 1 evidence that, LPM as an adjunct to standard of care, significantly closed more venous leg ...

9. researchgate.net researchgate.net/publication/397134037_Real_world_evidence_retrospective_study_to_evaluate_the_safety_and_efficacy_of_an_amniotic_membrane_allograft_for_venous_leg_ulcers_in_a_post-acute_care_setting

(PDF) Real world evidence retrospective study to evaluate ... Real world evidence retrospective study to evaluate the safety and efficacy of an amniotic membrane allograft for venous leg ulcers in a post- ...