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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PEP-TISSEEL, a fibrin sealant, for individuals with diabetic foot ulcers. Diabetic foot ulcers are painful sores on the feet that can be difficult to heal. The trial compares PEP-TISSEEL with standard treatment to determine if it promotes better and faster healing of the ulcers. Suitable participants have diabetes and a persistent foot ulcer that has not healed for at least four weeks despite standard care. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that PEP-TISSEEL is likely to be safe for humans?

Research has shown that PEP-TISSEEL has been tested for other health issues, and results suggest it is generally well-tolerated. In one study with patients who had long-lasting wounds, no serious side effects were reported, indicating the treatment might be safe for people.

As this study is in its early stages, it primarily focuses on assessing the treatment's safety. Treatments at this stage typically demonstrate some level of safety, but further research is necessary to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for diabetic foot ulcers?

PEP-TISSEEL is unique because it combines a fibrin sealant with advanced wound care dressings to potentially enhance the healing of diabetic foot ulcers. Unlike standard treatments, which typically rely on collagen-based dressings like Fibracol, PEP-TISSEEL's fibrin sealant may accelerate tissue repair by mimicking the body's natural clotting process, promoting better wound closure. Researchers are excited about PEP-TISSEEL because this new mechanism of action could lead to faster and more effective healing, improving outcomes for patients with this challenging condition.

What evidence suggests that PEP-TISSEEL might be an effective treatment for diabetic foot ulcers?

Research has shown that PEP-TISSEEL holds promise for treating diabetic foot ulcers. One study found that 81% of patients experienced complete healing of their ulcers within 6 months, increasing to 100% by 12 months. In this trial, participants in the PEP-TISSEEL+SOC arm will receive PEP-TISSEEL, which combines PEP (Platelet Exosome Product) with TISSEEL to aid blood clotting and potentially accelerate healing. This combination aims to enhance wound healing by supporting cell growth and tissue repair. While these early results are encouraging, further research is underway to confirm its effectiveness. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06319287

Study Details | NCT06319287 | Phase 2a Multi-Center ... The objective of this multi-center, prospective, randomized controlled study is to evaluate the safety and efficacy of PEP-TISSEEL+ Standard of Care (SOC)

2. withpower.com withpower.com/trial/phase-2-diabetic-foot-1-2024-6c9dd

PEP-TISSEEL for Diabetic Foot Ulcers 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11676782/

An Overview of Recent Clinical Trials for Diabetic Foot Ulcer ... Specifically, 81% of patients achieved full ulcer closure at 6 months, and this increased to 100% by 12 months [44]. Furthermore, Doppler ...

4. biospace.com biospace.com/rion-announces-initiation-of-phase-2a-clinical-study-for-purified-exosome-product-pep-in-diabetic-foot-ulcers

RION Announces Initiation of Phase 2A Clinical Study for ... RION's Phase 2A clinical trial focuses on evaluating the safety and efficacy of Platelet Exosome Product™ (PEP™) combined with TISSEEL fibrin ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06793748

NCT06793748 | Study to Evaluate the Safety, Tolerability ... Study to Evaluate the Safety, Tolerability, and Efficacy of PEP-TISSEEL in Subjects With Chronic Radiation Ulcer. ClinicalTrials.gov ID NCT06793748. Sponsor ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3626385/

Treatment of Nonhealing Diabetic Lower Extremity Ulcers ... No ulcer recurrence was noted in those patients during the follow-up period of 2 to 19 months. In this study, the combination of autologous platelet gel and ...

7. cms.gov cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=Y&NCAId=260

NCA - Autologous Blood-Derived Products for Chronic Non ... The objective of this study was to evaluate the safety and incidence of complete wound healing as well as wound recidivism rates among healed wounds in the ...