Phase II Study to Evaluate Efficacy and Safety of AMP Peptide PL-5 in Mild Infections of Diabetic Foot Ulcers

This is a Phase II, randomized, double-blind, placebo-controlled, multi-center study to evaluate the clinical efficacy and safety of Antimicrobial Peptide PL-5 Topical Spray in patients with mild infections of diabetic foot ulcers. Eligible subjects will be randomized (1:1:1) to receive twice a day, 14 days treatment of Antimicrobial Peptide PL-5 Topical Spray (1‰), Antimicrobial Peptide PL-5 Topical Spray (2‰) and topical placebo (vehicle) spray. In this study, the cut-off date for final analysis is defined as the time when all subjects have completed the last visit or discontinued the study

This is a Phase II, randomized, double-blind, placebo-controlled, multi-center study to evaluate the clinical efficacy and safety of Antimicrobial Peptide PL-5 Topical Spray in patients with mild infections of diabetic foot ulcers. Approximately 90 patients (30 per treatment group) will be randomized in this study. Eligible subjects will be randomized (1:1:1) to receive twice a day, 14 days treatment of Antimicrobial Peptide PL-5 Topical Spray (1‰), Antimicrobial Peptide PL-5 Topical Spray (2‰) and placebo of Antimicrobial Peptide PL-5 Topical Spray (vehicle). In this study, the cut-off date for final analysis is defined as the time when all subjects have completed the last visit or discontinued the study. The duration of the whole study is planned for 24 months; the duration of each participant is about 4-5 weeks, including Screening period/Baseline (about 7 days), treatment period (about 14 days), Follow-up period (about 7-14 days). No interim analysis will be performed in this study. This study is a phase II study, and no statistical hypothesis is proposed.

Eligibility Criteria:
Inclusion Criteria:

1. Age between 18 to 65 years.
2. Non-hospitalized ambulatory subjects with Diabetes mellitus, Type I or II, according to the American Diabetes Association criteria.
3. HbA1c ≤12% at screening.
4. At baseline visit (after any required debridement), presence of Grade 2 diabetic foot infection \[Grade 2 of the International Working Group on the Diabetic Foot (IWGDF) classification\]

   Infection present, as defined by the presence of at least 2 of the following items:
   * Local swelling or induration
   * Erythema \>0.5 cm to ≤2 cm around the ulcer.
   * Local tenderness or pain
   * Local increased warmth
   * Purulent discharge (thick, opaque to white, or sanguineous secretion)

   Mild infection of an ulcer is defined as:

   Presence of ≥2 manifestations of inflammation (purulence or erythema, tenderness, warmth, or induration), but any cellulitis/erythema extends ≤2cm around the ulcer, and infection is limited to the skin or superficial subcutaneous tissues; no other local complications or systemic illness.
5. Voluntary written consent, given before performance of any clinical investigation-related procedure not part of standard medical care, and with the understanding that consent may be withdrawn at any time without prejudice to future medical care.
6. Female subjects must meet at least one of the following additional criteria:

   * Surgically sterile with bilateral tubal ligation or hysterectomy.
   * Postmenopausal for at least one year.
   * If of childbearing potential, practicing an acceptable method of birth control for the duration of the clinical investigation as judged by the Investigator, such as condoms, foams, jellies, diaphragm, intrauterine device or abstinence

Exclusion Criteria:

1. Another cause of the inflammatory response of the skin around the ulcer (such as a trauma, gout, acute Charcot neuro-arthropathy, fracture, thrombosis, or venous stasis).
2. Foot deformities, calluses, corns, ingrown nails, fungal infections, which will impact infection or wound healing based on Investigator's judgement.
3. Received any topical or systemic antimicrobial therapy within 7 days prior to study entry (Day 1).
4. Infected diabetic foot ulcer that is associated with local wound complications such as prosthetic materials or protruding surgical hardware.
5. \> 1 infected foot ulcer.
6. Concurrent or expected to require systemic antimicrobials during the study period for any infection, including diabetic foot ulcer.
7. Bone or joint involvement is suspected based on clinical examination or plain X-ray.
8. Arterial brachial index (ABI) \<0.5 or ankle pressure \<50 mmHg. If ABI is \>1.3 (medial calcification is present), then only subjects meeting secondary testing requirements including either a toe pressure ≥30 mmHg, a transcutaneous pressure of oxygen ≥50 mmHg, or a skin perfusion pressure ≥40 mmHg are allowed. For subjects with ABI \>1.3, only the initial secondary test after ABI should be used for this assessment. A documented ABI within 3 months prior to Screening is acceptable, as is the initially performed secondary testing method for subjects with ABI \>1.3.
9. The subject is expected to be unable to care for the ulcer or return for all scheduled visits because of hospitalization, vacation, disability, etc. during the study period or cannot safely monitor the infection status at home.
10. Pregnant or lactating women.