AFS vs. AHC Grafts for Flesh-Eating Disease

(NF Trial)

Overseen By Colleen Brennan, MPH,BSN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Kerecis Ltd.

Disqualifiers: Other study participation, NPWT device inapplicable

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 9 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Necrotizing Fasciitis (NF) is a potentially life-threatening soft tissue infection. This study is comparing acellular fish skin graft (AFS) to standard of care allograft (AHC) in the treatment of NF. The purpose of this study is to compare clinical outcomes and time until autograft take in patients that were treated with AHC or AFS prior to permanent autografting to treat NF.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the idea that AFS vs. AHC Grafts for Flesh-Eating Disease is an effective treatment?

The available research shows that acellular fish skin grafts (AFS) are effective in treating wounds, including those from flesh-eating disease. AFS is made from the skin of Atlantic cod and helps wounds heal by supporting new tissue growth. One study highlighted its use in treating leg wounds from necrotizing fasciitis, a type of flesh-eating disease, showing faster healing and better outcomes. Another study noted that AFS reduced pain and hospital stay for children needing skin grafts. While there is no direct comparison to acellular human cadaver allografts (AHC) for flesh-eating disease, AFS has shown promising results in similar wound treatments. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment AFS (Acellular Fish Skin Graft) for flesh-eating disease?

Acellular fish skin grafts (AFS) have been shown to improve wound healing by supporting tissue regeneration and reducing healing time in various wound types, including those from necrotizing fasciitis (flesh-eating disease). They are rich in omega-3, which helps with tissue repair, and have been used successfully in both adults and children for different types of wounds, suggesting their potential effectiveness for treating flesh-eating disease. ^{1 2 3 4 5}

What safety data exists for AFS and AHC grafts?

Acellular fish skin grafts (AFS) have been studied in various clinical applications, including wound healing in both adults and children, with no known transmission of prion, bacterial, or viral diseases from North-Atlantic cod to humans. They are FDA cleared and CE marked, indicating a recognized level of safety. Studies have shown their use in reducing operating times, post-operative complications, and pain. There is no specific safety data provided for acellular human cadaver allografts (AHC) in the provided research. ^{1 2 4 6 7}

Is the acellular fish skin graft safe for use in humans?

Acellular fish skin grafts (FSGs) are considered safe for use in humans, as they are cleared by the US Food and Drug Administration for various wound treatments and have no known risk of transmitting diseases from North-Atlantic cod to humans. They have been used successfully in both adults and children, with no reported safety issues in the studies reviewed. ^{1 2 4 6 7}

Is the treatment AFS, AHC a promising treatment for flesh-eating disease?

Yes, AFS and AHC are promising treatments because they use advanced materials like Acellular Fish Skin Graft and Acellular Human Cadaver Allograft, which can help in tissue repair and healing. ^{8 9 10 11 12}

How does the treatment AFS and AHC differ from other treatments for flesh-eating disease?

AFS (Acellular Fish Skin Graft) and AHC (Acellular Human Cadaver Allograft) are unique because they use biological materials from fish skin and human cadavers, respectively, to help heal wounds. These treatments are different from traditional methods as they provide a natural scaffold for tissue regeneration, potentially improving healing in severe cases like flesh-eating disease. ^{8 9 10 11 12}

Research Team

Bounthavy Homsombath, M.D

Principal Investigator

Joseph M.Still Research Foundation

Eligibility Criteria

Adults over 18 with stable Necrotizing Fasciitis, treated at specific centers, can join this trial. It's not for those already in a drug/device study or with wounds where Negative Pressure Wound Therapy can't be applied due to location.

Inclusion Criteria

Has been admitted to the Joseph M. Still Burn Center at Doctors Hospital Augusta or Advanced Wound Clinic for treatment of NF which has been treated and is considered stable

Exclusion Criteria

Index wounds that due to anatomical location are unable to apply a NPWT device.

Subject has been previously enrolled into this study or is currently participating in another drug or device study that has not reached its primary endpoint

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Acellular Fish Skin (AFS) or Acellular Human Cadaver (AHC) with Negative Pressure Wound Therapy (NPWT) to prepare the wound bed prior to autografting

9 weeks

Weekly visits with +/- 4 days interval

Autograft Monitoring

Participants are monitored for autograft take after the wound is ready for autografting

Up to 9 visits

Long-term Follow-up

Participants are monitored at months 3, 6, and 9 post autograft placement for long-term outcomes

Treatment Details

Interventions

• AFS
• AHC

Trial Overview The trial is testing if Acellular Fish Skin Graft (AFS) leads to better healing and quicker readiness for permanent grafting compared to the standard Human Cadaver Allograft (AHC), both used alongside negative pressure wound therapy.

Participant Groups

Group I: Treatment: Acellular Fish Skin (AFS) with Standard of Care Negative Pressure Wound Therapy (NPWT) Experimental Treatment 1 Intervention

Eligible subjects will be randomized electronically to either the Acellular Fish Skin (AFS)arm. The subject will undergo wound bed preparation by surgical debridement. the AFS will be applied to the wound bed and secured with sutures, the size of the AFS will be determined after surgical debridement. Once the AFS is in place a Negative Pressure Wound Therapy device will be placed. the subject will be monitored weekly on scheduled intervals of +/- 4 days post AFS placement to assess the status of the wound and readiness for autografting. Once the wound is ready for autografting the subject will be monitored for autograft take, for up to 9 visits. Long term follow-up will be done at month 3, 6, 9 post autograft placement

Group II: Acellular Human Cadaver with Standard of Care Negative Pressure Wound Therapy (NPWT) Active Control 1 Intervention

.Eligible subjects will be randomized electronically to standard of care arm which is Acellular Human Cadaver (AHC) The subject will undergo wound bed preparation by surgical debridement. The AHC will be applied to the wound bed and secured with sutures, the size of the AHC will be determined after surgical debridement. Once the AHC is in place a Negative Pressure Wound Therapy device will be placed. the subject will be monitored weekly on scheduled intervals of +/- 4 days post AHC placement to assess the status of the wound and readiness for autografting. Once the wound is ready for autografting the subject will be monitored for autograft take, for up to 9 visits. Long term follow-up will be done at month 3, 6, 9 post autograft placement

AFS is already approved in United States, European Union for the following indications:

Approved in United States as Acellular Fish Skin Graft for:

• Wound care for necrotizing fasciitis

Approved in European Union as Acellular Fish Skin Graft for:

• Wound care for necrotizing fasciitis

Who Is Running the Clinical Trial?

Kerecis Ltd.

Lead Sponsor

Trials

14

Recruited

2,200+

Joseph M. Still Research Foundation, Inc.

Collaborator

Trials

9

Recruited

360+

Findings from Research

Acellular fish skin grafts (FSGs) derived from Atlantic cod are effective for wound healing, supporting tissue regeneration and revascularization, and are safe as they do not transmit known diseases to humans.

FSGs are the only acellular dermal matrix products not derived from mammals and have been successfully used in both adult and pediatric patients, including a case where a 7-year-old boy's abdominal wall wound healed effectively with FSG treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fish Skin Graft: Narrative Review and First Application for Abdominal Wall Dehiscence in Children. Di Mitri, M., Di Carmine, A., Thomas, E., et al.[2023]

In a study of 15 pediatric patients using a novel acellular fish skin graft (FSG) derived from cod, rapid wound healing was achieved, with 100% wound area coverage and 95% complete healing, significantly reducing the time to engraftment from an average of 21 days to 12 days when combined with negative pressure wound therapy (NPWT).

The use of FSG resulted in shorter operating times (less than 60 minutes), no reported complications or allergic reactions, and excellent pliability of healed wounds, making it a promising and sustainable option for pediatric skin grafting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of acellular intact fish skin grafts in treating acute paediatric wounds during the COVID-19 pandemic: a case series. Ciprandi, G., Kjartansson, H., Grussu, F., et al.[2022]

The autologous homologous skin construct (AHSC) successfully closed all 15 wounds in a diverse group of patients with various wound types using a single application, demonstrating its efficacy in skin repair.

Biopsies of the treated areas showed that AHSC resulted in mature, full-thickness skin with features like hair follicles and glands, indicating that the regenerated tissue closely resembles native skin without any reported adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Homologous Skin Constructs Allow Safe Closure of Wounds: A Retrospective, Noncontrolled, Multicentered Case Series. Mundinger, GS., Armstrong, DG., Smith, DJ., et al.[2021]

The use of an acellular fish skin matrix on donor sites for skin grafts in head and neck cancer surgeries significantly reduced healing time from an average of 68 days to 32 days, demonstrating its efficacy in promoting faster recovery.

Additionally, the fish skin matrix led to lower pain levels and eliminated local infections, with infection rates dropping from 60% to 0%, highlighting its potential safety benefits in wound care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acellular fish skin matrix on thin-skin graft donor sites: a preliminary study. Badois, N., Bauër, P., Cheron, M., et al.[2022]

Intact fish skin grafts (iFSGs) showed promising results in promoting wound granulation and providing pain relief in two patients with extensive leg ulcers following necrotizing fasciitis, with no complications or allergic reactions reported.

The application of iFSGs was easy and led to excellent functional and cosmetic outcomes after subsequent autologous skin grafting, suggesting their potential as a valuable treatment option for necrotizing fasciitis and possibly other wound types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Intact Fish Skin Grafts in the Treatment of Necrotizing Fasciitis of the Leg: Early Clinical Experience and Literature Review on Indications for Intact Fish Skin Grafts. Dueppers, P., Bozalka, R., Kopp, R., et al.[2023]

Acellular fish skin shows great potential as a tissue-engineered scaffold for clinical applications, particularly in artificial skin, surgical patches, and wound dressings, although no research has been reported in China yet.

While the development of products based on acellular fish skin is considered clinically feasible and necessary, further foundational research is needed to ensure its safety and efficacy in medical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[NEW PROGRESS OF ACELLULAR FISH SKIN AS NOVEL TISSUE ENGINEERED SCAFFOLD]. Wei, X., Wang, N., He, L., et al.[2019]

Acellular fish skin grafts (FSGs) were used successfully on 13 dogs and 4 cats with complex wounds, leading to complete healing in most cases without any reported adverse events.

The median time for wounds to heal after the first FSG application was 71 days, and the application process was straightforward, requiring no special training or equipment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acellular fish skin grafts for the management of wounds in dogs and cats: 17 cases (2019-2021). Mauer, ES., Maxwell, EA., Cocca, CJ., et al.[2022]

In a study involving rabbits, researchers successfully created vascularized island flaps using cryopreserved allogeneic vascular bundles, demonstrating their potential as effective vascular pedicles for tissue transfer.

After 8 days, the implanted vascular bundles showed successful integration with the recipient's native vessels, leading to viable flaps, indicating that cryopreserved vascular bundles can support tissue survival and healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental study of allogeneically vascularized prefabricated flaps. Hirai, T., Manders, EK., Hughes, K., et al.[2019]

Arterioarterial grafts (AAGs) can be a viable alternative for hemodialysis in patients who have exhausted other vascular access options, showing satisfactory dialysis adequacy across eight studies involving 151 patients.

The primary patency rates for AAGs were between 67%-94.5% at six months and 54%-61% at 36 months, indicating a reasonable longevity for this graft type, especially with end-to-side configurations that did not lead to distal ischemia upon occlusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An arterioarterial prosthetic graft as an alternative option for haemodialysis access: a systematic review. Grima, MJ., Vriens, B., Holt, PJ., et al.[2022]

The use of human acellular vessels (HAV) as a conduit for vascular access in hemodialysis shows promise in improving safety and efficacy for patients with end-stage renal disease, particularly in complex cases where standard options are limited.

In a high-risk population with significant comorbidities, the technical success of surgeries using HAV for aneurysm repairs suggests that this regenerative medicine approach could expand treatment options for patients needing vascular access.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded Utility of Human Acellular Vessel in Hemodialysis Access Surgery and Arterial Aneurysm Repair. Nickerson, MC., Thamba, A., Rao, V., et al.[2023]

In a study involving nine patients who required arteriovenous fistulae for hemodialysis, nine autogenous vein grafts (AVG) were successfully used, demonstrating a potential solution for patients lacking suitable vessels.

However, three grafts failed within 3 to 14 months, and complications such as thrombosis and false aneurysms occurred, indicating that while AVG can be effective, they may also present significant risks and require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular access for haemodialysis with autogenous vein graft arteriovenous fistulas. Lindfors, O., Eklund, B., Kock, B.[2004]

The study of 20 patients using dimethyl sulfoxide-cryopreserved cadaveric vein allografts for hemodialysis showed a significant increase in panel reactive antibody (PRA) values, indicating broad allosensitization, with a mean PRA of 84.1% after an average of 3.1 months.

In contrast, a control group of 20 matched patients on a kidney transplant waiting list had a mean PRA of only 5.5%, with no conversions from nonreactive to reactive PRA, suggesting that these allografts pose a risk for potential kidney transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of cryopreserved cadaveric vein allograft for hemodialysis access precludes kidney transplantation because of allosensitization. Benedetto, B., Lipkowitz, G., Madden, R., et al.[2013]

References

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

Fish Skin Graft: Narrative Review and First Application for Abdominal Wall Dehiscence in Children. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Use of acellular intact fish skin grafts in treating acute paediatric wounds during the COVID-19 pandemic: a case series. [2022]

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

Autologous Homologous Skin Constructs Allow Safe Closure of Wounds: A Retrospective, Noncontrolled, Multicentered Case Series. [2021]

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

Acellular fish skin matrix on thin-skin graft donor sites: a preliminary study. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Use of Intact Fish Skin Grafts in the Treatment of Necrotizing Fasciitis of the Leg: Early Clinical Experience and Literature Review on Indications for Intact Fish Skin Grafts. [2023]

6. China pubmed.ncbi.nlm.nih.gov

[NEW PROGRESS OF ACELLULAR FISH SKIN AS NOVEL TISSUE ENGINEERED SCAFFOLD]. [2019]

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

Acellular fish skin grafts for the management of wounds in dogs and cats: 17 cases (2019-2021). [2022]

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

Experimental study of allogeneically vascularized prefabricated flaps. [2019]

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

An arterioarterial prosthetic graft as an alternative option for haemodialysis access: a systematic review. [2022]

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

Expanded Utility of Human Acellular Vessel in Hemodialysis Access Surgery and Arterial Aneurysm Repair. [2023]

11. Finland pubmed.ncbi.nlm.nih.gov

Vascular access for haemodialysis with autogenous vein graft arteriovenous fistulas. [2004]

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

Use of cryopreserved cadaveric vein allograft for hemodialysis access precludes kidney transplantation because of allosensitization. [2013]