PEP-TISSEEL for Diabetic Foot Ulcers

Overseen By Maureen Merrifield, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rion Inc.

Must not be taking: Antibiotics, Immunosuppressants, Corticosteroids

Disqualifiers: Chemotherapy, Charcot foot, HIV, 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: 1

Duration: 12 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a special glue-like substance called PEP-TISSEEL combined with usual treatments on patients with non-healing diabetic foot ulcers. The goal is to see if this combination helps wounds heal better by sticking tissues together and promoting faster healing.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently on or require antibiotics, or if you are taking immunosuppressive agents, except for stable low doses of corticosteroids. It's best to discuss your specific medications with the trial team.

How is the PEP-TISSEEL treatment different from other treatments for diabetic foot ulcers?

PEP-TISSEEL is unique because it is a fibrin sealant, which means it uses proteins to help blood clot and seal wounds, potentially speeding up the healing process. This is different from other treatments like antibiotics or dressings, which focus on infection control or wound coverage. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for individuals with diabetic foot ulcers. Specific criteria aren't provided, but typically participants would need to have a confirmed diagnosis of DFU and be in stable health otherwise.

Inclusion Criteria

Must meet one of the following criteria:

- Dorsal transcutaneous oxygen measurement (TCOM/TcPO2) measurement of ≥ 40 mmHg within 90 days of Screening (Visit 1 or 2)

My wound is between 1 cm2 and 15 cm2 after cleaning.

Exclusion Criteria

I cannot or will not use the specified support device.

I have an active case of Charcot foot.

I had surgery to improve blood flow in my limb within the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive PEP-TISSEEL+SOC or SOC only treatment for diabetic foot ulcers

12 weeks

Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• PEP-TISSEEL

Trial Overview The study is testing PEP-TISSEEL, applied topically on diabetic foot ulcers. It's designed to see if this treatment is safe and works well (efficacy) compared to other treatments or placebos.

Participant Groups

Group I: PEP-TISSEEL+SOC Active Control 1 Intervention

Treatment for the PEP-TISSEEL+SOC arm is: * PEP-TISSEEL * Mepitel dressing followed by Tegaderm® (Mepilex can be used if subjects are allergic to Tegaderm) * 3M Cavilon® (may be used on the borders prior to placing the Tegaderm or Mepilex) * Padded 3-layer secondary outer layer dressing (Profore (Smith and Nephew (Memphis, TN)); and * Offloaded with an offloading Controlled Ankle Movement (CAM) Boot (Foot Defender (Miami, FL) or Total Contact Cast (TCC)) Use of an alternate offloading device (e.g., Charcot Restraint Orthotic Walker (CROW) boot, custom shoe, etc.) may be approved on a case-by-case basis

Group II: Standard of Care Placebo Group 1 Intervention

* Fibracol * Mepitel dressing followed by Tegaderm (Mepilex can be used if subjects are allergic to Tegaderm) * 3M Cavilon (may be used on the borders prior to placing the Tegaderm or Mepilex ) * Padded 3-layer secondary outer layer dressing (Profore (Smith and Nephew (Memphis, TN)) or equivalent); and * Offloaded with an offloading CAM Boot (Foot Defender (Miami, FL) or TCC) * Use of an alternate offloading device (e.g., Charcot Restraint Orthotic Walker (CROW) boot, custom shoe, etc.) may be approved on a case-by-case basis

PEP-TISSEEL is already approved in United States, European Union for the following indications:

Approved in United States as TISSEEL for:

• Hemostasis
• Sealing of colonic anastomoses following reversal of temporary colostomies

Approved in European Union as TISSEEL for:

• Hemostasis
• Sealing of colonic anastomoses following reversal of temporary colostomies

Who Is Running the Clinical Trial?

Rion Inc.

Lead Sponsor

Trials

4

Recruited

260+

Professional Education and Research Institute

Collaborator

Trials

16

Recruited

1,400+

Findings from Research

In treating ischemic diabetic ulcers, distinguishing between limb-threatening and non-limb-threatening infections is crucial, with Staphylococcus aureus being a common pathogen for the latter, and appropriate antibiotic therapy can significantly impact healing outcomes.

Adjunctive therapies like granulocyte colony-stimulating factor and iloprost have shown benefits in reducing amputation rates and improving ulcer healing, highlighting the importance of a multifactorial approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Local care and medical treatment for ischemic diabetic ulcers]. Lazareth, I.[2022]

DSC127, a novel topical agent for diabetic foot ulcers (DFUs), is currently in Phase III clinical trials and has shown promising results in accelerating wound healing compared to the existing treatment, Regranex, which has limited efficacy.

The mechanism of action for DSC127 includes promoting cell proliferation, enhancing blood vessel formation, and improving collagen deposition and skin regeneration, making it a potentially effective treatment for chronic wounds in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NorLeu3-Angiotensin (1-7) [DSC127] as a Therapy for the Healing of Diabetic Foot Ulcers. Rodgers, KE., Bolton, LL., Verco, S., et al.[2019]

In a study of 50 diabetic patients with foot ulcers, those treated with Mepilex Lite dressings healed significantly faster (median 49.9 days) compared to those using vaseline gauze (median 65.5 days), indicating better efficacy for Mepilex Lite.

While there was no significant difference in pain levels between the two groups, Mepilex Lite dressings were effective in reducing the wound area, suggesting they may enhance the healing process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of diabetic foot ulcers using Mepilex Lite Dressings: a pilot study. Zhang, Y., Xing, SZ.[2014]

Hyperbaric oxygen therapy (HBOT) significantly improves healing rates and reduces the risk of major amputations in patients with diabetic foot ulcers, based on a systematic review of 18 studies involving 1526 patients.

The evidence for other adjunctive therapies, such as arterial pump devices and pharmacologic agents like iloprost and pentoxifylline, is limited and does not show significant benefits compared to conventional treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of adjunctive therapies in diabetic foot ulcers. Elraiyah, T., Tsapas, A., Prutsky, G., et al.[2022]

The incidence of diabetic foot ulcers (DFU) is rising globally, making effective treatment crucial to prevent infections and amputations.

The TLC-NOSF dressing, which combines lipidocolloid technology with nano-oligosaccharide factors, has shown effectiveness in managing DFU, supporting its use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uso de apósitos con TLC-NOSF en el manejo de la úlcera de pie diabético, basado en la revisión de la evidencia y la práctica clínica. Sagüez, FS., Gallardo, RC., Pozo, AP.[2021]

References

1. France pubmed.ncbi.nlm.nih.gov

[Local care and medical treatment for ischemic diabetic ulcers]. [2022]

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

NorLeu3-Angiotensin (1-7) [DSC127] as a Therapy for the Healing of Diabetic Foot Ulcers. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Treatment of diabetic foot ulcers using Mepilex Lite Dressings: a pilot study. [2014]

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

A systematic review and meta-analysis of adjunctive therapies in diabetic foot ulcers. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Uso de apósitos con TLC-NOSF en el manejo de la úlcera de pie diabético, basado en la revisión de la evidencia y la práctica clínica. [2021]