Fish Skin Graft for Venous Leg Ulcers

(THOR Trial)

Overseen By Thomas Serena, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Kerecis Ltd.

Must not be taking: Immunosuppressants, Chemotherapy, Biologics, others

Disqualifiers: End stage renal disease, Pregnancy, others

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

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

Compensation: Varies

Number of Visits: 12

Duration: 12 weeks

150 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the between-arm difference in the proportion of subjects achieving complete closure of hard-to-heal venous leg ulcers (VLU) between Intact Fish Skin Graft plus standard of care (IFSG/SOC) versus standard of care alone (SOC) over 12 weeks.

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, high-dose corticosteroids, or chemotherapy, you may not be eligible to participate.

What data supports the effectiveness of the treatment Intact Fish Skin Graft for venous leg ulcers?

Research shows that fish skin grafts rich in omega-3 fatty acids, like Kerecis Omega3, have been effective in healing chronic wounds, such as diabetic foot ulcers, faster than standard treatments. These grafts help wounds heal quicker by reducing inflammation and providing a protective barrier against bacteria. ^{1 2 3 4 5}

Is the fish skin graft treatment safe for humans?

The fish skin graft treatment, used under various names like Kerecis Omega3, has been evaluated in different studies for conditions such as diabetic foot wounds and necrotizing fasciitis. These studies suggest that the treatment is generally safe, with benefits like faster healing and reduced complications, although specific safety data for venous leg ulcers is not detailed. ^{1 2 5 6 7}

How is the fish skin graft treatment for venous leg ulcers different from other treatments?

The fish skin graft treatment is unique because it uses acellular fish skin rich in omega-3 fatty acids, which help in faster wound healing and provide anti-inflammatory benefits. Unlike traditional skin grafts, this treatment offers a natural barrier against bacteria and promotes better healing outcomes. ^{1 2 3 6 8}

Eligibility Criteria

This trial is for adults over 18 with nonhealing venous leg ulcers present for at least 4 weeks, but not treated with high-level compression for more than a year. The ulcer must be between 1 and 25 cm2 post-debridement. Participants need adequate blood flow as indicated by specific tests (ABI, TBI, TCOM, PVR). Those with multiple ulcers can join if the largest one meets these conditions.

Inclusion Criteria

I am 18 years old or older.

My TBI score is 0.6 or higher.

I have a leg ulcer that hasn't healed in over 4 weeks and haven't had long-term compression treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Intact Fish Skin Graft plus standard of care or standard of care alone for nonhealing venous leg ulcers

12 weeks

Up to 12 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Intact Fish Skin Graft

Trial Overview The study aims to see if adding Intact Fish Skin Graft (IFSG) to standard wound care helps heal tough venous leg ulcers better than just standard care alone. Patients are split into two groups: one receives IFSG/SOC and the other only SOC, and their healing progress is compared over a period of 12 weeks.

Participant Groups

Group I: Intact Fish Skin Graft (IFSG) + Standard of Care Experimental Treatment 1 Intervention

Up to 12 visits with Intact Fish Skin Graft (IFSG) + Standard of Care.

Group II: Standard of Care Active Control 1 Intervention

Standard of care will be cleaning, debridement, ulcer moisture balance, and offloading.

Intact Fish Skin Graft is already approved in European Union, United States for the following indications:

Approved in European Union as Kerecis Omega3 for:

• Second-degree burn wounds
• Chronic wounds
• Venous leg ulcers
• Diabetic foot ulcers

Approved in United States as Kerecis Omega3 for:

• Second-degree burn wounds
• Chronic wounds
• Venous leg ulcers
• Diabetic foot ulcers

Who Is Running the Clinical Trial?

Kerecis Ltd.

Lead Sponsor

Trials

14

Recruited

2,200+

Serena Group

Collaborator

Trials

6

Recruited

790+

Serena Group

Collaborator

Trials

6

Recruited

790+

Findings from Research

In a study of eight diabetic patients with postoperative foot wounds, the use of an intact fish skin graft rich in omega-3 resulted in over 84.9% reduction in wound area for wounds less than three months old after six weeks of treatment.

No infections or adverse skin reactions were reported, indicating that the fish skin graft is safe and may be an effective adjunct treatment for accelerating healing in diabetic foot wounds, especially when applied early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of diabetic foot wounds with acellular fish skin graft rich in omega-3: a prospective evaluation. Woodrow, T., Chant, T., Chant, H.[2019]

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 grafts from Atlantic cod, rich in omega-3 fatty acids like EPA and DHA, have shown increased efficacy in treating chronic, non-healing wounds such as diabetic foot ulcers, leading to faster healing rates compared to standard treatments.

The unique lipid profile of fish skin grafts not only promotes wound closure but also provides barrier protection against bacteria and modulates the inflammatory response, enhancing overall wound healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fish Skin Grafts with Omega-3 for Treatment of Chronic Wounds: Exploring the Role of Omega-3 Fatty Acids in Wound Healing and A Review of Clinical Healing Outcomes. Seth, N., Chopra, D., Lev-Tov, H.[2022]

In a study involving 94 patients with diabetic foot ulcers, the use of acellular fish skin grafts resulted in a significantly higher healing rate of 63.0% compared to 31.3% for the standard collagen alginate dressing after 12 weeks (P = 0.0036).

Both treatment groups had a similar mean healing time of 7 weeks, but the fish skin graft required a median of 6 applications to achieve healing, indicating its potential as an effective alternative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the effect of omega-3-rich fish skin in the treatment of chronic, nonresponsive diabetic foot ulcers: penultimate analysis of a multicenter, prospective, randomized controlled trial. Lullove, EJ., Liden, B., McEneaney, P., et al.[2022]

In a study of 51 patients with hard-to-heal venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs), the use of intact fish skin grafts (FSGs) led to faster healing than predicted by standard care (SOC), with some wounds healing over 50% sooner.

FSGs were particularly effective for wounds that were unlikely to heal with SOC, demonstrating the potential to change the healing trajectory even for wounds that initially increased in size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faster Than Projected Healing in Chronic Venous and Diabetic Foot Ulcers When Treated with Intact Fish Skin Grafts Compared to Expected Healing Times for Standard of Care: An Outcome-Based Model from a Swiss Hospital. Zehnder, T., Blatti, M.[2022]

The Kerecis™ Omega3 Wound matrix, derived from fish skin, was used to treat 25 complicated wounds in 23 patients, showing effectiveness in promoting healing where conventional treatments had failed.

Patients experienced a reduction in analgesic intake after starting treatment with the Omega3 Wound matrix, suggesting potential pain-relieving benefits alongside its wound healing properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The marine Omega3 wound matrix for treatment of complicated wounds: A multicenter experience report. Dorweiler, B., Trinh, TT., Dünschede, F., et al.[2022]

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]

In a study of 51 patients with diabetic foot ulcers, the use of acellular fish skin grafts resulted in an impressive 87.57% reduction in wound surface area over 16 weeks, with 60.34% of wounds fully healed.

The findings support previous research indicating that acellular fish skin grafts can effectively promote wound healing by facilitating the transition from chronic to acute healing stages, particularly showing rapid improvement in the first 4 weeks after application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acellular Fish Skin Graft Use for Diabetic Lower Extremity Wound Healing: A Retrospective Study of 58 Ulcerations and a Literature Review. Michael, S., Winters, C., Khan, M.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Treatment of diabetic foot wounds with acellular fish skin graft rich in omega-3: a prospective evaluation. [2019]

2. 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]

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

Fish Skin Grafts with Omega-3 for Treatment of Chronic Wounds: Exploring the Role of Omega-3 Fatty Acids in Wound Healing and A Review of Clinical Healing Outcomes. [2022]

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

Evaluating the effect of omega-3-rich fish skin in the treatment of chronic, nonresponsive diabetic foot ulcers: penultimate analysis of a multicenter, prospective, randomized controlled trial. [2022]

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

Faster Than Projected Healing in Chronic Venous and Diabetic Foot Ulcers When Treated with Intact Fish Skin Grafts Compared to Expected Healing Times for Standard of Care: An Outcome-Based Model from a Swiss Hospital. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

The marine Omega3 wound matrix for treatment of complicated wounds: A multicenter experience report. [2022]

7. 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]

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

Acellular Fish Skin Graft Use for Diabetic Lower Extremity Wound Healing: A Retrospective Study of 58 Ulcerations and a Literature Review. [2020]