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

A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of Antimicrobial Peptide PL-5 Topical Spray in Patients With 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

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Foot Ulcers
• Intervention / Treatment: Drug: Antimicrobial Peptide PL-5 Topical Spray and Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Vista, California, United States, 92081
      • ILD Research Center
  • Florida
    • Miami, Florida, United States, 33175
      • Bioresearch Partner Holdings, LLLP
    • Tampa, Florida, United States, 33615
      • Santos Research Center, CORP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Antimicrobial Peptide PL-5 Topical Spray: 1 mg/g (1‰); Eligible subjects will be randomized (1:1:1) to receive twice a day, 14 days treatment of Antimicrobial Peptide PL-5 Topical Spray (1‰)	Drug: Antimicrobial Peptide PL-5 Topical Spray and Placebo; Antimicrobial Peptide PL-5 Topical Spray At about 5 cm vertically above the wound, the investigator sprays antimicrobial peptide PL-5 topical spray on the test wound. The cover area after spraying is a cone with a surface diameter of about 5 cm and area about 20 cm2. One spray dose is about 0.1 ml. The number of drug sprays is determined according to the wound area in the screening period, and the determined dose is applied consistently. During the operation, an effective spray operation is completely ejected with no leakage.; Other Names: AMP PL-5 and Placebo
Experimental: Antimicrobial Peptide PL-5 Topical Spray:2 mg/g (2‰); Eligible subjects will be randomized (1:1:1) to receive twice a day, 14 days treatment of Antimicrobial Peptide PL-5 Topical Spray (2‰)	Drug: Antimicrobial Peptide PL-5 Topical Spray and Placebo; Antimicrobial Peptide PL-5 Topical Spray At about 5 cm vertically above the wound, the investigator sprays antimicrobial peptide PL-5 topical spray on the test wound. The cover area after spraying is a cone with a surface diameter of about 5 cm and area about 20 cm2. One spray dose is about 0.1 ml. The number of drug sprays is determined according to the wound area in the screening period, and the determined dose is applied consistently. During the operation, an effective spray operation is completely ejected with no leakage.; Other Names: AMP PL-5 and Placebo
Placebo Comparator: Topical placebo (vehicle); Eligible subjects will be randomized (1:1:1) to receive twice a day, 14 days treatment of Antimicrobial Placebo of Antimicrobial Peptide PL-5 Topical Spray (vehicle).	Drug: Antimicrobial Peptide PL-5 Topical Spray and Placebo; Antimicrobial Peptide PL-5 Topical Spray At about 5 cm vertically above the wound, the investigator sprays antimicrobial peptide PL-5 topical spray on the test wound. The cover area after spraying is a cone with a surface diameter of about 5 cm and area about 20 cm2. One spray dose is about 0.1 ml. The number of drug sprays is determined according to the wound area in the screening period, and the determined dose is applied consistently. During the operation, an effective spray operation is completely ejected with no leakage.; Other Names: AMP PL-5 and Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	the Investigator will grade the clinical response as （1）"infection resolved or cured" (all signs and symptoms of infection resolved);（2）"infection improving"(most, but not all, signs and symptoms of infection improved or resolved)（3）"treatment failure" (≥1 signs or symptoms of infection substantially worsening), (4)"unevaluable"(<3 days of study treatment or patient lost to follow-up), or （5）"recurrence"(a previously cured or improved infection showing worsening of signs or symptoms of infection)	At EOT (End-of-therapy: within 24 hours after the final dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiological response	Microbiological culture examination of wound tissue; Analysis of drug sensitivity test results; Analysis of MIC50, MIC90, geometric mean inhibitory concentration and range results of clinically isolated pathogenic bacteria. At baseline, day 1, and at all other study visits, Investigators will culture samples obtained from the wound at which culturable material and signs of infection are present. They will obtain specimens using tissue curettage with a sterile scalpel, place them into transport media, and ship them to the designated central laboratory for species identification and antibiotic susceptibility testing. For specific operations of bacteriological examination of wound tissue, please refer to the clinical microbiology operation manual. Result: 1）Resolved;2） Improved;3)Failure 4） Colonization 5） Superinfection.	Interim Clinical Evaluation (ICE): 7 days after the initiation of the study drug. End of Therapy (EOT): within 24 hours after the final dose. Post-therapy evaluation (PTE): 7-14 days after the final dose.
Comprehensive Response	At EOT and PTE, the Investigator will grade the comprehensive response as （1）"cure"(patients are clinically cured, and the bacteria are eradicated or presumed eradicated.);（2）"failure" (patients are classified as clinical failure or/and microbiological responses are failure and superinfection) or （3）"indeterminate"(if both clinical and microbiological responses are indeterminate).	End of Therapy (EOT): within 24 hours after the final dose. Post-therapy evaluation (PTE):7-14 days after the final dose.
Safety and tolerability	The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), and clinically significant changes in physical examination, vital signs, laboratory tests, and 12-lead electrocardiogram (ECG)	Interim Clinical Evaluation (ICE): 7 days after the initiation of the study drug. End of Therapy (EOT): within 24 hours after the final dose. Post-therapy evaluation (PTE): 7-14 days after the final dose
Clinical response	At each visit after enrollment, the Investigator will grade the clinical response as （1）"infection resolved or cured" (all signs and symptoms of infection resolved);（2）"infection improving"(most, but not all, signs and symptoms of infection improved or resolved)（3）"treatment failure" (≥1 signs or symptoms of infection substantially worsening), (4)"unevaluable"(<3 days of study treatment or patient lost to follow-up), or （5）"recurrence"(a previously cured or improved infection showing worsening of signs or symptoms of infection)	Interim Clinical Evaluation (ICE): 7 days after the initiation of the study drug. End of Therapy (EOT): within 24 hours after the final dose. Post-therapy evaluation (PTE): 7-14 days after the final dose.
Wound infection Score and Total Wound Score	A "wound infection score" was semiquantitatively assessed by grading each of 7 parameters with a score of 0-3: (1) purulent drainage, (2) nonpurulent drainage, (3) erythema, (4) induration, (5) tenderness, (6) pain, and (7) local warmth.	At baseline, day 1, and at all other study visits, investigators will compile a "total wound score" that included ratings of signs and symptoms of infection, wound measurements (maximum length, width, and depth), and assessment of granulation tissue.

Collaborators and Investigators

• Sponsor: Jiangsu ProteLight Pharmaceutical & Biotechnology Co., Ltd.
• Collaborators: Parexel
• Investigators: Study Chair: Mingxia Chen, MD, MS, Jiangsu Protelight Pharmaceutical & Biotechnology Co., Ltd

Publications and helpful links

General Publications

• Wei Y, Li Y, Li X, Zhao Y, Xu J, Wang H, Rong X, Xiong J, Chen X, Luo G, Lv G, Lin C, Han C, Yu H, Zhang Y, Tang S, Fan Y, Tu J, Xia C, Zu H, Liu W, Liu C, Liu J, Zhang B, Nong Q, Li T, Wang L, Song G, Su Y, Chen Z, Lai W, Fu Y, Yu J, Zhang P, Yang W, Yao G, Zhang H, Fan K, Dong H, Chen Y, Wu J; PL-5 Investigators. Peceleganan Spray for the Treatment of Skin Wound Infections: A Randomized Clinical Trial. JAMA Netw Open. 2024 Jun 3;7(6):e2415310. doi: 10.1001/jamanetworkopen.2024.15310.
• Wei Y, Wu J, Chen Y, Fan K, Yu X, Li X, Zhao Y, Li Y, Lv G, Song G, Rong X, Lin C, Wang H, Chen X, Zhang P, Han C, Zu H, Liu W, Zhang Y, Liu C, Su Y, Zhang B, Sun B, Wang L, Lai W, Liu J, Xia C, Ji G, Zhu F, Yu J, Ahemaiti A, Dong H, Chen M; PL-5 Investigators. Efficacy and Safety of PL-5 (Peceleganan) Spray for Wound Infections: A Phase IIb Randomized Clinical Trial. Ann Surg. 2023 Jan 1;277(1):43-49. doi: 10.1097/SLA.0000000000005508. Epub 2022 Jul 4.

Helpful Links

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Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: December 19, 2023
• First Posted (Actual): January 3, 2024

Study Record Updates

• Last Update Posted (Actual): May 25, 2025
• Last Update Submitted That Met QC Criteria: May 23, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Diabetic; Diabetic Foot Infection; Diabetic Foot; Wound Infection
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Diabetes Mellitus; Diabetic Angiopathies; Diabetes Complications; Skin Diseases; Skin Ulcer; Leg Ulcer; Diabetic Neuropathies; Foot Diseases; Ulcer; Infections; Diabetic Foot; Foot Ulcer; Anti-Bacterial Agents; Anti-Infective Agents
• Other Study ID Numbers: 280800-JSPL-PL-5-203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No