Phase 2a Multi-Center Prospective, Randomized Trial to Evaluate the Safety & Efficacy of Topical PEP-TISSEEL for Diabetic Foot Ulcers (DFU)

NCT06319287 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: PRO-00125
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2a Multi-Center, Prospective, Randomized, Controlled Study aimed to evaluate the Safety and Efficacy of Topically Applied PEP-TISSEEL in Subjects with Diabetic Foot Ulcers (DFU)

Conditions

Diabetic Foot Ulcer

Keywords

Diabetic Foot Ulcer; Diabetic Wound; Diabetic Foot; Foot Ulcer; Exosome; Extracellular Vesicle

Outcome Measures

Primary Outcomes (2)

• Wound Closure

  Complete wound closure (wound healing) by 12 weeks (efficacy; landmark analysis)

  12 weeks

• Safety

  Count dose limiting toxicity events (incidence of treatment-emergent adverse event)

  6 months

Secondary Outcomes (1)

• Percent Area Reduction of Wound at 12 Weeks

  12 weeks

Other Outcomes (3)

• Visual Analogue Scale (VAS) for Pain over 12 weeks

  12 weeks

• Semmes-Weinstein Score

  12 weeks

• Wound-Q Scale

  12 weeks

Study Arms (2)

PEP-TISSEEL+SOC

ACTIVE COMPARATOR

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

Biological: PEP (Purified Exosome Product) / TISSEEL

Standard of Care

SHAM COMPARATOR

* 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

Biological: PEP (Purified Exosome Product) / TISSEEL

Interventions

PEP (Purified Exosome Product) / TISSEEL BIOLOGICAL

PEP Drug Product is a lyophilized powder contained within a 10R glass vial. PEP Drug Product is a lyophilized powder derived from apheresed platelets in plasma. The powder cake weighs approximately 75 mg per vial. This protocol will evaluate 2 vials of PEP Drug Product delivered in 10 mL TISSEEL fibrin sealant (15mg/mL PEP-TISSEEL) for 12 weeks. TISSEEL is a fibrin sealant indicated as an adjunct to standard surgical techniques (such as suture and ligature) to prevent leakage from colonic anastomoses following the reversal of temporary colostomies

Also known as: Extracellular Vesicles

PEP-TISSEEL+SOC; Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥ 18 years of age
• Properly obtained written informed consent
• Documented history of Type I or Type II Diabetes Mellitus, requiring oral and/or insulin replacement therapy
• The index ulcer is classified as Wagner grade 1 ulcer and remains Wagner 1 Grade between Screening and Randomization/Baseline visit (Visit 1 through Visit 3)
• These ulcers are superficial, full-thickness ulcers limited to the dermis, not extending to the subcutaneous tissue
• Area of index ulcer must be between 1 cm2 to 15 cm2 post debridement at screening and baseline
• The index ulcer must be located anatomically on the foot with ≥ 50% of the wound area below the medial or lateral malleolus
• Presence of a persistent nonhealing DFU for at least 4 weeks from Randomization and not more than 1 year that has failed to respond to SOC at any point during this timeframe
• Adequate vascular perfusion as evidenced by one of the following:
• Dorsal transcutaneous oxygen measurement (TCOM/TcPO2) measurement of
• ≥ 40 mmHg within 90 days of Screening (Visit 1 or 2)
• Ankle Branchial Index (ABI) between 0.7 and 1.3 within 90 days of Screening (Visit 1 or 2) using the extremity on which the index ulcer is located
• Arterial Doppler ultrasound evaluating for biphasic or triphasic dorsalis pedis and/or posterior tibial vessels at the level of the ankle or a TBI (Toe Brachial Index) of \> 0.6 is acceptable within 90 days of Screening (Visit 1 or 2)
• The index ulcer has been offloaded with protocol defined offloading device during Screening (Run-In) period through Randomization/Baseline visit.
• Must meet one of the following criteria:

You may not qualify if:

• Actively undergoing chemotherapy treatment (localized radiation treatment is allowed if it is not on the DFU wound site and in remission based on scans, bloodwork or some other kind of test, such as a breast biopsy or a bone marrow biopsy)
• Ulceration with exposed tendon, capsule, or bone
• Suspicion of bone or joint infection by clinical or other criteria as per STONEES criteria below:
• a. STONEES criteria for infection: i. size increase, ii. temperature elevation, iii. os (probe to bone) iv. new areas of breakdown v. exudative vi. erythema/edema vii. smell
• Unable or unwilling to utilize the protocol defined offloading device
• Subjects who have undergone endovascular or open revascularization of the index limb within the last 30 days from Screening.
• Index ulcer has decreased in area by ≥ 30% between Screening (Visit 1) and Baseline visits
• Any subject that is currently on/or requires oral, systemic or topical antibiotics, or is anticipated to require their use during the course of the study
• Any subject that has vascular compromise requiring surgical intervention or has undergone vascular reconstruction or angioplasty less than 1 month prior to randomization. Any planned surgical procedures during the study participation
• Serum Creatinine level \> 3.0 mg/dL
• Hemoglobin A1c (HbA1c) \>12%
• Aspartate Aminotransferase (AST, GOT) and/or Alanine Aminotransferase (ALT, GPT) \>3x the upper limit of normal
• Acute active Charcot foot
• The location of the index ulcer is within 2 cm of any other ulcer
• Any subject that would be unable to safely monitor the infection status of the index ulcer at home and return for scheduled visits

Sponsors & Collaborators

• Rion Inc.: lead
• Professional Education and Research Institute: collaborator

Study Sites (1)

Professional Education & Research Institute (PERI)

Blue Ash, Ohio, 45242, United States

Location

Related Links

• Rion company website
• PERI company website

MeSH Terms

Conditions

Diabetic Foot; Foot Ulcer

Interventions

Fibrin Tissue Adhesive

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies; Foot Diseases

Intervention Hierarchy (Ancestors)

Fibrin; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multi-center, Open Label, Randomized Controlled Clinical Trial Evaluating the Effect of PEP/TISSEEL in the Treatment of Diabetic Foot Ulcers

Study Record Dates

• First Submitted: March 13, 2024
• First Posted: March 20, 2024
• Study Start: February 27, 2024
• Primary Completion: April 23, 2025
• Study Completion: November 1, 2025
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)