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

Inclusion Criteria:

1. Males and females ≥ 18 years of age

2. Properly obtained written informed consent

3. Documented history of Type I or Type II Diabetes Mellitus, requiring oral and/orinsulin replacement therapy

4. The index ulcer is classified as Wagner grade 1 ulcer and remains Wagner 1 Gradebetween Screening and Randomization/Baseline visit (Visit 1 through Visit 3)

5. These ulcers are superficial, full-thickness ulcers limited to the dermis, notextending to the subcutaneous tissue

6. Area of index ulcer must be between 1 cm2 to 15 cm2 post debridement at screeningand baseline

7. The index ulcer must be located anatomically on the foot with ≥ 50% of the woundarea below the medial or lateral malleolus

8. Presence of a persistent nonhealing DFU for at least 4 weeks from Randomization andnot more than 1 year that has failed to respond to SOC at any point during thistimeframe

9. Adequate vascular perfusion as evidenced by one of the following:

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

11. 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

12. Arterial Doppler ultrasound evaluating for biphasic or triphasic dorsalis pedisand/or posterior tibial vessels at the level of the ankle or a TBI (ToeBrachial Index) of > 0.6 is acceptable within 90 days of Screening (Visit 1 or

10. The index ulcer has been offloaded with protocol defined offloading device duringScreening (Run-In) period through Randomization/Baseline visit.

11. Must meet one of the following criteria: a. Female subjects of Non-Child-Bearing Potential defined as: i. Postmenopausal forat 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 toScreening (Visit 1 or 2), or iii. Must have a negative serum β-hCG pregnancy test atVisit 1 and not be breastfeeding prior to being administered with the study drug b.Male subjects of Non-Childbearing Potential are defined as those vasectomizedsubjects whose vasectomy was performed 6 months prior to Screening (Visit 1 or 2) orthose diagnosed as sterile by a physician c. Females and Males of ChildbearingPotential who practice an acceptable method of contraception defined as the use ofany form of hormonal contraceptive, a barrier method with spermicide, condoms,intrauterine device, or abstinence from sexual intercourse starting at least 60 daysprior 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 anadditional urine test at Baseline/Randomization (Visit 3 or Day 0) and must not bebreastfeeding prior to being administered with the study drug

12. Ability to comply with the study protocol as per investigator discretion

Exclusion Criteria:

1. Actively undergoing chemotherapy treatment (localized radiation treatment is allowedif it is not on the DFU wound site and in remission based on scans, bloodwork orsome other kind of test, such as a breast biopsy or a bone marrow biopsy)

2. Ulceration with exposed tendon, capsule, or bone

3. Suspicion of bone or joint infection by clinical or other criteria as per STONEEScriteria 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

4. Unable or unwilling to utilize the protocol defined offloading device

5. Subjects who have undergone endovascular or open revascularization of the index limbwithin the last 30 days from Screening.

6. Index ulcer has decreased in area by ≥ 30% between Screening (Visit 1) and Baselinevisits

7. 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

8. Any subject that has vascular compromise requiring surgical intervention or hasundergone vascular reconstruction or angioplasty less than 1 month prior torandomization. Any planned surgical procedures during the study participation

9. Serum Creatinine level > 3.0 mg/dL

10. Hemoglobin A1c (HbA1c) >12%

11. Aspartate Aminotransferase (AST, GOT) and/or Alanine Aminotransferase (ALT, GPT) >3xthe upper limit of normal

12. Acute active Charcot foot

13. The location of the index ulcer is within 2 cm of any other ulcer

14. Any subject that would be unable to safely monitor the infection status of the indexulcer at home and return for scheduled visits

15. History of immunosuppression or taking immunosuppressive agents including systemiccorticosteroids, except stable daily doses of 5 mg/day or less for chronicconditions for up to 5 days

16. Any subject with a life expectancy ≤ 6 months

17. Pregnancy, including a positive pregnancy test at Baseline, orlactation/breastfeeding at anytime

18. Use of investigational drugs or biologics within 28 days prior to screening (Visit 1or 2)

19. History of a concurrent condition that, in the Investigator's opinion, wouldjeopardize the safety of the subject or compliance with the protocol

20. Known or suspected active abuse of alcohol, or non-prescription drugs

21. Participation in another interventional clinical study or study in the past 30 daysof Screening (Visit 1 or 2) or concurrent participation in another interventionalclinical study

22. Subjects who have untreated Hep C

23. Subjects who are HIV positive

24. Subjects on anticoagulation that are not maintained within the InternationalNormalized Ratio (INR) of > 3.0