Diabetic Foot UlcerPhase 2NCT06319287
Phase 2a Multi-Center Prospective, Randomized Trial to Evaluate the Safety & Efficacy of Topical PEP-TISSEEL for Diabetic Foot Ulcers (DFU)
A Phase 2 study testing PEP (Purified Exosome Product) / TISSEEL in people with Diabetic Foot Ulcer, run by Rion Inc. at 1 site in United States.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Foot Ulcer
- What is being tested?
- PEP (Purified Exosome Product) / TISSEEL
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Feb 2024to 1 Nov 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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:
- Female subjects of Non-Child-Bearing Potential defined as: i. Postmenopausal for at least 1 year (Subject verbal confirmation acceptable), or surgically sterilized (i.e., hysterectomy or bilateral oophorectomy more than 3 months prior to Screening (Visit 1 or 2)), or ii. Bilateral tubal ligation more than 6 months prior to Screening (Visit 1 or 2), or iii. Must have a negative serum β-hCG pregnancy test at Visit 1 and not be breastfeeding prior to being administered with the study drug b. Male subjects of Non-Childbearing Potential are defined as those vasectomized subjects whose vasectomy was performed 6 months prior to Screening (Visit 1 or 2) or those diagnosed as sterile by a physician c. Females and Males of Childbearing Potential who practice an acceptable method of contraception defined as the use of any form of hormonal contraceptive, a barrier method with spermicide, condoms, intrauterine device, or abstinence from sexual intercourse starting at least 60 days prior to Screening and continuing at least 30 days following the last treatment.
- Female will undergo a negative serum β-hCG pregnancy test at Visit 1 and an additional urine test at Baseline/Randomization (Visit 3 or Day 0) and must not be breastfeeding prior to being administered with the study drug
- Ability to comply with the study protocol as per investigator discretion
Who cannot join
- 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:
- 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.
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- 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
- History of immunosuppression or taking immunosuppressive agents including systemic corticosteroids, except stable daily doses of 5 mg/day or less for chronic conditions for up to 5 days
- Any subject with a life expectancy ≤ 6 months
- Pregnancy, including a positive pregnancy test at Baseline, or lactation/breastfeeding at anytime
- Use of investigational drugs or biologics within 28 days prior to screening (Visit 1 or 2)
- History of a concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the subject or compliance with the protocol
- Known or suspected active abuse of alcohol, or non-prescription drugs
- Participation in another interventional clinical study or study in the past 30 days of Screening (Visit 1 or 2) or concurrent participation in another interventional clinical study
- Subjects who have untreated Hep C
- Subjects who are HIV positive
- Subjects on anticoagulation that are not maintained within the International Normalized Ratio (INR) of > 3.0
Trial locations and contacts
1 site in 1 country.
United States1 site
Professional Education & Research Institute (PERI)
Blue Ash, Ohio, 45242
About this study
Official title: A Phase 2a Multi-Center, Prospective, Randomized Controlled Study to Evaluate the Safety and Efficacy of Topically Applied PEP-TISSEEL in Subjects With Diabetic Foot Ulcers (DFU)
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)
Read the detailed description
The objective of this multi-center, prospective, randomized controlled study is to evaluate the safety and efficacy of PEP-TISSEEL+ Standard of Care (SOC) compared to SOC only treatment in up to 60 subjects (30 subjects PEP-TISSEEL + SOC and 30 subjects SOC only), specifically for the treatment of their non-healing DFU.
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
Treatment for the Standard of Care (SOC) only arm is:
- 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
- Conditions
- Diabetic Foot Ulcer
- Being tested
- PEP (Purified Exosome Product) / TISSEEL
- Keywords
- Diabetic Foot Ulcer, Diabetic Wound, Diabetic Foot, Foot Ulcer, Exosome, Extracellular Vesicle
- Medical subject headings
- Diabetic Foot, Foot Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PEP (Purified Exosome Product) / TISSEELBiological
Also called Extracellular Vesicles
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Biological: PEP (Purified Exosome Product) / TISSEEL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Wound Closure
Complete wound closure (wound healing) by 12 weeks (efficacy; landmark analysis)
Measured: 12 weeks
Dose Limiting Toxicities
Count dose limiting toxicity events.
Measured: 12 week treatment + 3 month (12 weeks) non-dosing Safety Follow-Up
Secondary outcomes (1)
Percent Area Reduction of Wound at 12 Weeks
Percentage area reduction (PAR) at 12 weeks.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2024
- Study start27 Feb 2024
- Primary completion23 Apr 2025
- Study completion1 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetic Foot UlcerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multi-center, Open Label, Randomized Controlled Clinical Trial Evaluating the Effect of PEP/TISSEEL in the Treatment of Diabetic Foot Ulcers
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rion Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Professional Education and Research Institute
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06319287
- Sponsor's protocol ID
- PRO-00125
- Status last verified
- Jun 2026
- First submitted
- 13 Mar 2024
- Last updated
- 20 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a Multi-Center, Prospective, Randomized Controlled Study to Evaluate the Safety and Efficacy of Topically Applied PEP-TISSEEL in Subjects With Diabetic Foot Ulcers (DFU)
- ClinicalTrials.gov ID
- NCT06319287
- Acronym / sponsor ID
- PRO-00125
- Conditions
- Diabetic Foot Ulcer
- Keywords
- Diabetic Foot Ulcer, Diabetic Wound, Diabetic Foot, Foot Ulcer, Exosome, Extracellular Vesicle
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Rion Inc.Industry (pharma, biotech, devices)
- Collaborators
- Professional Education and Research Institute
- Study start
- 27 Feb 2024 (actual)
- Primary completion
- 23 Apr 2025 (actual)
- Study completion
- 1 Nov 2025 (actual)
- First posted
- 20 Mar 2024 (actual)
- Results
- Posted 20 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Detailed description
The objective of this multi-center, prospective, randomized controlled study is to evaluate the safety and efficacy of PEP-TISSEEL+ Standard of Care (SOC) compared to SOC only treatment in up to 60 subjects (30 subjects PEP-TISSEEL + SOC and 30 subjects SOC only), specifically for the treatment of their non-healing DFU.
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
Treatment for the Standard of Care (SOC) only arm is:
- 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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Multi-center, Open Label, Randomized Controlled Clinical Trial Evaluating the Effect of PEP/TISSEEL in the Treatment of Diabetic Foot Ulcers
| Arm | Type | Receives |
|---|---|---|
| PEP-TISSEEL+SOC | Active comparator | Biological: PEP (Purified Exosome Product) / TISSEELTreatment 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 |
| Standard of Care | Sham comparator | Biological: PEP (Purified Exosome Product) / TISSEEL* 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (25 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PEP (Purified Exosome Product) / TISSEELAlso: Extracellular VesiclesPEP 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 | Biological | PEP-TISSEEL+SOC, Standard of Care |
Primary outcome
Complete Wound Closure
Time frame: 12 weeks
Complete wound closure (wound healing) by 12 weeks (efficacy; landmark analysis)
Dose Limiting Toxicities
Time frame: 12 week treatment + 3 month (12 weeks) non-dosing Safety Follow-Up
Count dose limiting toxicity events.
1 secondary outcome
Percent Area Reduction of Wound at 12 Weeks
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Rion company websiteLink provided by the sponsor.
- PERI company websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PEP (Purified Exosome Product) / TISSEEL in people with Diabetic Foot Ulcer, run by Rion Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Wound Closure (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2026.