Nu-3 Gel for Infected Diabetic Foot Ulcers

• ClinicalTrials.gov Identifier: NCT06020235
• Recruitment Status: Not yet recruiting
• First Posted: August 31, 2023
• Last Update Posted: March 12, 2024
• Sponsor: Lakewood-Amedex Inc
• Information provided by (Responsible Party): Lakewood-Amedex Inc

Tracking Information

• First Submitted Date: August 8, 2023
• First Posted Date: August 31, 2023
• Last Update Posted Date: March 12, 2024
• Estimated Study Start Date: December 2024
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 27, 2023)

• Safety [ Time Frame: Day 0 to Day 28 ]
  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
• Efficacy [ Time Frame: Day 0 to Day 14 ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 27, 2023)

• Treatment failure rate per treatment regimen [ Time Frame: Day 0 to Day 14 ]
  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.
• Treatment failure rate per treatment regimen [ Time Frame: Day 0 to Day 14 ]
  Number of treatment failures, defined as need to switch to oral antibiotic treatment based on clinical wound-infection assessment by the PI, per cohort
• Safety [ Time Frame: Day 0 to Day 28 ]
  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
• Safety [ Time Frame: Day 0 to Day 28 ]
  Change in parameters indicative of skin irritation and/or skin sensitization compared to baseline
• Pharmacokinetics [ Time Frame: Day 0 to Day 13 ]
  Maximum concentration in the first 20 patients sampled for PK across all dosing groups after initial and repeated dosing

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: August 27, 2023)

• Wound healing [ Time Frame: Day 0 to Day 28 ]
  Percentage area reduction of wound size at Day 7, Day 14, and Day 28 compared to baseline
• Wound healing [ Time Frame: Day 0 to Day 28 ]
  Change in the 5-component clinical signs DFI score at all timepoints compared to baseline
• Wound healing [ Time Frame: Day 0 to Day 28 ]
  Change in the overall DFI score at all timepoints compared to baseline

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Nu-3 Gel for Infected Diabetic Foot Ulcers
• Official Title: 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)

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Diabetic Foot Infection

Intervention

• Drug: 5% Nu-3 gel
  The gel is called Nu-3 which is either applied once per day or twice per day to the infected ulcer.
• Drug: 10% Nu-3 gel
  The gel is called Nu-3 which is either applied once per day or twice per day to the infected ulcer.
• Drug: Placebo
  Placebo gel is either applied once per day or twice per day to the infected ulcer.

Study Arms

• Experimental: 5% Nu-3 gel once daily
  The 5% Nu-3 gel is applied once per day and placebo is applied once per day.
  Interventions:

  • Drug: 5% Nu-3 gel
  • Drug: Placebo
• Experimental: 5% Nu-3 gel twice daily
  The 5% Nu-3 gel is applied twice per day.
  Intervention: Drug: 5% Nu-3 gel
• Experimental: 10% Nu-3 gel once daily
  The 10% Nu-3 gel is applied once per day and placebo is applied once per day.
  Interventions:

  • Drug: 10% Nu-3 gel
  • Drug: Placebo
• Experimental: 10% Nu-3 gel twice daily
  The 10% Nu-3 gel is applied twice per day.
  Intervention: Drug: 10% Nu-3 gel
• Placebo Comparator: Placebo
  The placebo is applied twice per day.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: August 27, 2023): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2025
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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:

  1. Dorsal transcutaneous oxygen measurement (TCOM) or a skin perfusion pressure (SPP) measurement of ≥ 40 mmHg
  2. Ankle Branchial Index (ABI) between 0.9 and 1.3 within 3 months of Screening using the extremity with the target ulcer.

  3. 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Thomas Balzer; 941-225-2516 ext 108; tbalzer@lakewoodamedex.com

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT06020235
• Other Study ID Numbers: LAI-Nu-3-CLIN004
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Lakewood-Amedex Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Lakewood-Amedex Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Lakewood-Amedex Inc
• Verification Date: August 2023