Nu-3 Gel for Infected Diabetic Foot Ulcers

Diabetic Foot Infection Clinical Trial

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06020235
• Other study ID #: LAI-Nu-3-CLIN004
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 2024
• Est. completion date: August 2025

Study information

• Verified date: August 2023
• Source: Lakewood-Amedex Inc
• Contact: Thomas Balzer
• Phone: 941-225-2516
• Email: tbalzer[@]lakewoodamedex.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: August 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Diabetic Foot
• Diabetic Foot Infection
• Foot Ulcer

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.
• 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.
• Placebo
Placebo gel is either applied once per day or twice per day to the infected ulcer.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Lakewood-Amedex Inc

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Wound healing	Percentage area reduction of wound size at Day 7, Day 14, and Day 28 compared to baseline	Day 0 to Day 28
Other	Wound healing	Change in the 5-component clinical signs DFI score at all timepoints compared to baseline	Day 0 to Day 28
Other	Wound healing	Change in the overall DFI score at all timepoints compared to baseline	Day 0 to Day 28
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Safety	Change in parameters indicative of skin irritation and/or skin sensitization compared to baseline	Day 0 to Day 28
Secondary	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