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

Trial Summary

What is the purpose of this trial?

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. Other research purposes include the following: * Rate of wound closure * Change in ulcer size over 12 weeks * Any adverse events or reactions (side effects) * Change in pain levels * Occurrence of infection

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.

What data supports the effectiveness of the treatment E-GRAFT™, FIBRACOL™ for venous leg ulcers?

Research shows that using amniotic membrane grafts, like those in E-GRAFT™, can significantly improve healing in venous leg ulcers. In one study, 62% of patients treated with a similar allograft showed over 40% wound closure in 4 weeks, compared to 32% with standard therapy alone. ^{1 2 3 4 5}

Is the amnion membrane allograft safe for treating venous leg ulcers?

Research shows that using amnion membrane allografts for venous leg ulcers is generally safe. Studies report no significant safety concerns, and the treatment has properties like reducing inflammation and pain, and promoting healing. ^{1 2 6 7 8}

How does the treatment E-GRAFT™ differ from other treatments for venous leg ulcers?

E-GRAFT™ uses an amnion membrane allograft, which contains growth factors and proteins that help heal chronic ulcers. This treatment is unique because it promotes healing through natural components found in the amniotic membrane, offering a less costly and potentially more effective alternative to traditional skin grafts and other bioengineered skin substitutes. ^{1 3 5 7 9}

Research Team

Charles M Zelen, DPM FACFAS

Principal Investigator

Professional Education and Research Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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]

References

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

Use of amniotic membrane transplantation in the treatment of venous leg ulcers. [2022]

2. United States 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. [2022]

3. Colombia pubmed.ncbi.nlm.nih.gov

Healing of a chronic ulcer of the lower limb of venous origin with fresh human amniochorionic membrane allograft [2023]

4. France pubmed.ncbi.nlm.nih.gov

[Human amniotic membrane in the management of chronic venous leg ulcers]. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

Human acellular amniotic membrane is adopted to treat venous ulcers. [2020]

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

A Multicenter, Randomized, Controlled, Clinical Trial Evaluating Dehydrated Human Amniotic Membrane in the Treatment of Venous Leg Ulcers. [2023]

7. Portugal pubmed.ncbi.nlm.nih.gov

Amniotic Membrane in the Treatment of Varicose Ulcers: a Center Experience. [2019]

8. Spain pubmed.ncbi.nlm.nih.gov

Amniotic membrane transplantation in the treatment of chronic lower limb ulcers. [2012]

9. Spain pubmed.ncbi.nlm.nih.gov

[Cost-benefit analysis of amniotic membrane transplantation for venous ulcers of the legs that are refractory to conventional treatment]. [2018]