Nu-3 Gel for Infected Diabetic Foot Ulcers

Study Overview
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Brief Summary
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The goal of this clinical trial is to test a topical drug in patients with mild infections of their diabetic foot ulcer. The main questions it aims to answer are: What strength does the drug need to be in order to make the infection better? How frequently does the drug need to be applied in order to make the infection better? Participants will be asked to apply the medicine on their foot ulcer twice a day for 2 weeks and remain off of that foot during that time. Participants will receive the medication either once a day or twice a day, in either a 5% or 10% gel, or placebo. Researchers will compare the 5% and 10% gels to placebo to see if the infection improves.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate Safety and Antimicrobial Efficacy Of Topically Once Or Twice Daily Applied Bisphosphocin® Nu-3 Gel At 5% And 10% Concentrations To Infected Diabetic Foot Ulcers (iDFU)

Conditions
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Diabetic Foot Infection

Intervention / Treatment
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* Drug: 5% Nu-3 gel
* Drug: 10% Nu-3 gel
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Male and female subjects ≥18 years of age. 2. Voluntary written informed consent, including information about the provisions of the Health Insurance Portability and accountability act (HIPAA) as applicable. 3. Non-hospitalized ambulatory subjects diagnosed with diabetes mellitus, Type I or II per ADA criteria with signs of a localized mild foot infection as defined by the IDSA infection severity criteria (Lipsky,2012) a. the presence of purulent drainage or at least two of the following criteria: i. erythema, ii. warmth, iii. pain or tenderness, iv. edema, or v. induration (The diagnosis of mild infection must be confirmed immediately following debridement at Baseline). 4. The target ulcer is classified as a grade 1 ulcer according to the Wagner Scale (Wagner 1979). The ulcer is a superficial, full-thickness ulcer limited to the dermis, not extending to the subcutis. Target ulcer is >1 cm2 and <12 cm2 post debridement at baseline and must be no higher than the ankle, on or below the malleolus (ankle bone) with ≥50% below the malleolus. 5. Adequate vascular perfusion as evidenced by one of the following: Dorsal transcutaneous oxygen measurement (TCOM) or a skin perfusion pressure (SPP) measurement of ≥ 40 mmHg Ankle Branchial Index (ABI) between 0.9 and 1.3 within 3 months of Screening using the extremity with the target ulcer. Arterial Doppler ultrasound evaluating for biphasic or triphasic dorsalis pedis and posterior tibial vessels at the level of the ankle or a TBI (Toe Brachial Index) of >0.75. 6. Subject has a caregiver who will attend the Baseline visit (V2) and/or watch the dosing and dressing demonstration video and apply wound treatment along with study dressings for the study duration. 7. Must meet one of the following criteria: a. Female subjects of Non-Child-Bearing Potential i. Postmenopausal for at least 1 year ii. Surgically sterilized (i.e., hysterectomy or bilateral oophorectomy more than 3 months prior to Screening) iii. Bilateral tube ligation > 6 months prior to screening iv. A negative serum β-hCG pregnancy test at screening and no breastfeeding after the administration of the study drug. b. Male subjects of Non-Childbearing Potential defined as: i. Vasectomized subjects for > 6 months prior to Screening ii. Those diagnosed as sterile by a physician. c. Females and Males of Childbearing Potential who practice an acceptable method of contraception defined as the i. Use of any form of hormonal contraceptive ii. Use of a barrier method with spermicide, condoms, intrauterine device, iii. Abstinence from sexual intercourse starting at least 60 days prior to Screening and continuing at least 14 days following the last treatment. 8. Subjects must be willing to undergo all clinical investigation-related procedures, attend all required visits, and cooperate fully with the investigator and site personnel. 9. Subject must be willing to wear offloading RCW, if necessary, throughout the duration of the clinical treatment. 10. Subject must have plain radiograph taken at screening and prior to randomization showing no evidence of bony abnormalities consistent with osteomyelitis, or gas compatible with tissue crepitus, in the affected foot. Exclusion Criteria: 1. Ulceration with exposed tendon, capsule, or bone 2. IDSA-defined moderate or severe DFU infection. 3. Infected diabetic foot ulcer that is associated with local wound complication such as prosthetic materials or protruding surgical hardware. 4. > 1 infected foot ulcer 5. Subject is currently receiving topical antimicrobial treatment for a localized infection of the study ulcer and whose infection is improving in response to treatment. 6. Subject has received a systemic antibiotic within 48 hours prior to Screening. 7. Concurrent or expected to require systemic antimicrobials during the study period for any infection including diabetic foot ulcer. 8. Any subject that has active viral hepatitis (A, B, C) and/or untreated HIV/AIDS. 9. 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 10. eGFR <60 and/or subject on hemodialysis within 3 months prior to randomization. 11. Hemoglobin A1c (HbA1c) >12% within 3 months prior to randomization. 12. Aspartate Aminotransferase (AST, GOT) and/or Alanine Aminotransferase (ALT, GPT) >3.0 x the upper limit of normal and/or bilirubin >1.5 x the upper limit of normal within 3 months prior to randomization. 13. Acute active Charcot foot 14. Any subject that would be unable to safely monitor the infection status at home and return for scheduled visits. 15. History of immunosuppression within 3 months prior to randomization, or taking immunosuppressive agents including systemic corticosteroids, except stable daily doses of 5 mg/day or less for chronic conditions 16. Any subject with a life expectancy ≤ 6 months 17. Use of investigational drugs within 28 days prior to screening 18. Use of Aspirin® or acetylsalicylic acid containing medication (except low-dose aspirin) < 7 days before baseline, 19. Use of oral anticoagulants (e.g., warfarin, Xarelto® or comparable products). 20. History of concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the subject or compliance with the protocol including known or suspected active abuse of alcohol, narcotics, or non-prescription drugs. 21. Prior randomization in this clinical trial, or a previous Bisphosphocin study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5% Nu-3 gel once daily<br>The 5% Nu-3 gel is applied once per day and placebo is applied once per day. | Drug: 5% Nu-3 gel<br>* The gel is called Nu-3 which is either applied once per day or twice per day to the infected ulcer.<br>Drug: Placebo<br>* Placebo gel is either applied once per day or twice per day to the infected ulcer.<br>|
| Experimental: 5% Nu-3 gel twice daily<br>The 5% Nu-3 gel is applied twice per day. | Drug: 5% Nu-3 gel<br>* The gel is called Nu-3 which is either applied once per day or twice per day to the infected ulcer.<br>|
| Experimental: 10% Nu-3 gel once daily<br>The 10% Nu-3 gel is applied once per day and placebo is applied once per day. | Drug: 10% Nu-3 gel<br>* The gel is called Nu-3 which is either applied once per day or twice per day to the infected ulcer.<br>Drug: Placebo<br>* Placebo gel is either applied once per day or twice per day to the infected ulcer.<br>|
| Experimental: 10% Nu-3 gel twice daily<br>The 10% Nu-3 gel is applied twice per day. | Drug: 10% Nu-3 gel<br>* The gel is called Nu-3 which is either applied once per day or twice per day to the infected ulcer.<br>|
| Placebo Comparator: Placebo<br>The placebo is applied twice per day. | Drug: Placebo<br>* Placebo gel is either applied once per day or twice per day to the infected ulcer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Number of AEs overall and those assessed by the investigators as possibly, probably, and definitely related to the study drug; number of SAEs per patient and cohort | Day 0 to Day 28 | 
| Efficacy | The rate of reduction in CFUs by >=2 logs per pathogen identified as typical and highly suspicious for being the cause of the infection, in each treatment group compared to placebo group at Day 7 compared to Day 0, and Day 14 compared to Day 0. | Day 0 to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment failure rate per treatment regimen | The proportion of patients whose infection was not cured, defined as resolution of all wound infection signs, or whose infection did not improve over the course of the study defined as a lower number of clinical signs of infection or lower extent or severity as assesed by wound infection score. | Day 0 to Day 14 | 
| Treatment failure rate per treatment regimen | Number of treatment failures, defined as need to switch to oral antibiotic treatment based on clinical wound-infection assessment by the PI, per cohort | Day 0 to Day 14 | 
| Safety | Number of AEs (overall and those assessed by the investigators as possibly, probably and definitely related to the study drug) and SAEs per patient and cohort and clinically relevant changes in physical examination, vital signs, laboratory and/or ECG measurements at the defined timepoints compared to baseline | Day 0 to Day 28 | 
| Safety | Change in parameters indicative of skin irritation and/or skin sensitization compared to baseline | Day 0 to Day 28 | 
| Pharmacokinetics | Maximum concentration in the first 20 patients sampled for PK across all dosing groups after initial and repeated dosing | Day 0 to Day 13 |