A Study to Evaluate ENERGI-F703 GEL in Diabetic Foot Ulcer

Study Overview
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Brief Summary
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This Phase 3 study is a randomized, double-blind, vehicle-controlled, multiple-center, parallel study to evaluate efficacy and safety of ENERGI-F703 GEL compared with vehicle control in subjects with Wagner Grade 1 to Grade 2 diabetic foot ulcers. Baseline target ulcer size (<16 cm2 vs ≥16 cm2 ) will be included as a stratification factor. Subjects will be randomized 1:1 to receive ENERGI-F703 GEL or vehicle control using an interactive web response system for randomization to automatically assign a unique subject randomization number. Total duration of the study will be up to 31 weeks including Screening visit (approximately 2 to 3 weeks), double-blind dosing/observation phase (16 weeks), and a safety follow-up of 12 weeks after the last administration of study treatment.

Official Title
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A Randomized, Double-Blind, Vehicle-controlled, Parallel, Phase III Study to Evaluate Efficacy and Safety of ENERGI-F703 GEL in Subjects With Diabetic Foot Ulcers

Conditions
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Diabetic Foot Ulcer, Foot Ulcer, Diabetes Mellitus, Wound

Intervention / Treatment
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* Drug: ENERGI-F703 GEL
* Drug: ENERGI-F703 matched vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be at least 18 years old. Subject must have diagnosed with diabetes mellitus (DM), eg, currently under DM medication treatment or subjects with naïve DM with duplicated hemoglobin A1c over 6.5% and fasting plasma glucose over 126 mg/dL measured at least 1 week apart before screening. Subject must have at least 1 cutaneous ulcer on the foot and not healing for at least 4 weeks. The largest diabetic foot ulcer will be selected as target ulcer. If 2 or more ulcers have the largest size, the one with worst grade will be selected. If 2 or more ulcers have the largest size and grade, the one with longest duration will be selected. The target ulcer is classified as Grade 1 to Grade 2 ulcer according to Wagner Grading System and with ulcer size of 1.5 cm2 to 25 cm2. Diabetic foot ulcers should be free of any necrosis or infection Subject has signed the written informed consent form Male subjects must be surgically sterile (biologically or surgically) or commit to the use of a reliable method of birth control (must agree to use double-barrier contraception in the event of sexual activity) or be practicing abstinence for the duration of the study and for 30 days after study treatment administration. Female subjects are eligible only if all of the following apply: Not pregnant with a negative serum pregnancy test at Screening visit and negative urine pregnancy test within 24 hours before randomization (test not required for females of non-childbearing potential, defined as surgically sterile [eg, hysterectomy or bilateral oophorectomy] or postmenopausal [amenorrheic for at least 1 year]) Not lactating Not planning to become pregnant during the study If of childbearing potential, commits to the use of a highly effective method of contraception for the duration of the study and at least 30 days after study treatment administration. Exclusion Criteria: History or evidence of osteomyelitis as confirmed by the investigator. An x-ray/pathology assessment of debridement or a probe-to-bone (PTB) test will be used to determine presence of osteomyelitis. With target ulcer size decreased by at least 30% after at least 2 weeks of standard of care-only period between screening and randomization Subjects with highly exudated wounds which require dressing changes more than 3 times a day may be enrolled, but heavily exudated wounds should not be selected as target ulcers With poor nutritional status (serum albumin <2g/dL or prealbumin <10 mg/dL), poor diabetic control (hemoglobin A1c >12%), a leukocyte counts <2,000/mm3, abnormal liver function (aspartate aminotransferase, alanine aminotransferase >3 x upper limit of normal range) within 21 days before Randomization visit Requiring treatment with systemic corticosteroids, immunosuppressive or chemotherapeutic agents With known or suspected hypersensitivity to any ingredients of study product and vehicle With coronary heart disease with myocardial infarction, coronary artery bypass graft, or percutaneous transluminal coronary angioplasty within 3 months prior to study Known or suspected history of drug abuse or a recent history of alcohol abuse (regularly drinks >4 units of alcohol per day: 1 unit = 8 oz. beer, 3 oz. wine, or 1 oz. spirits) within 6 months prior to screening History or positive test results for HIV, presence of active Hepatitis B virus (HBV), or active Hepatitis C virus (HCV) Hepatitis B surface antigen positive at screening is exclusionary Subjects with history of past or resolved HBV infection or hepatitis B core antibody positive at screening are eligible if HBV DNA viral load ≤2000 IU/mL in the absence of antiviral therapy and during the previous 12 weeks prior to the viral load evaluation with normal transaminases values Subjects with a history of HCV infection or HCV antibody positive at screening are eligible if HCV viral load is below the level of detection Malignancy in the last 2 years, with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix Ankle brachial index <0.8 or >1.4 Enrollment in any investigational drug trial within 4 weeks before entering this study With any condition judged by the investigator that entering the trial may be detrimental to the subject -

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: ENERGI-F703 GEL<br>ENERGI-F703, topical application, 2 times daily for 16 weeks | Drug: ENERGI-F703 GEL<br>* Standard of care and ENERGI-F703 GEL are applied for the treatment of diabetic foot ulcers.<br>|
| Placebo Comparator: ENERGI-F703 matched vehicle<br>ENERGI-F703 matched vehicle, topical application, 2 times daily for 16 weeks | Drug: ENERGI-F703 matched vehicle<br>* Standard of care and ENERGI-F703 matched vehicle are applied for treatment of diabetic foot ulcers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ulcer complete closure rate | Proportion of subjects with a recording of complete ulcer closure at Week 16 (the end of the treatment period) as assessed by the investigator, where such closure is subsequently confirmed at 2 consecutive study visits over a 2-week period (ie, by Week 18). A complete ulcer closure is defined as 100% skin re epithelialization without drainage or dressing requirements. | Weeks 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time to ulcer closure | Time to ulcer closure in weeks, defined as the time from randomization to first record of complete closure, as assessed by the investigator, where complete closure is subsequently confirmed at 2 consecutive study visits over a 2-week period | Weeks 4, 6, 8, 10, 12, 14, and 16 | 
| The frequency and severity of adverse events | Frequency and severity of adverse events (AEs), including treatment emergent AEs, serious AEs, treatment-related AEs, and treatment-related serious AEs | Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, and 28 | 
| The proportion of subjects with complete ulcer closure | Proportion of subjects with confirmed complete ulcer closure as assessed by the investigator. | Weeks 4, 6, 8, 10, 12, 14, and 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Foot Ulcer, Diabetes Mellitus, Wound Healing