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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus; Foot Ulcer; Diabetic Foot Ulcer; Wound
• Intervention / Treatment: Drug: ENERGI-F703 matched vehicle; Drug: ENERGI-F703 GEL

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yifang Cheng, PhD; Phone Number: +886-2-26270835; Email: ct@energenesis-biomedical.com

Study Locations

• Taiwan
  • Chiayi City, Taiwan
    • Recruiting
    • Ditmanson Medical Foundation Chia-Yi Christian Hospital
    • Contact: Chien-Liang Fang, Dr.
  • Kaohsiung City, Taiwan
    • Recruiting
    • Kaohsiung Medical University Hospital
    • Contact: Shu-Hung Huang, Dr.
  • Taichung, Taiwan
    • Recruiting
    • China Medical University Hospital
    • Contact: Hsin-Han Chen, Dr.
  • Taichung, Taiwan
    • Recruiting
    • Taichung Veterans General Hospital
    • Contact: Yiling Lin, Dr.
  • Taichung, Taiwan
    • Recruiting
    • Kung Tien General Hospital
    • Contact: Shih-Ting Tseng, Dr.
  • Tainan City, Taiwan
    • Recruiting
    • National Cheng Kung University Hospital
    • Contact: Shin-Chen Pan, Dr.
  • Tainan City, Taiwan
    • Recruiting
    • Chi Mei Medical Center
    • Contact: Chun Chia Chen, Dr.
  • Taipei, Taiwan
    • Recruiting
    • Mackay Memorial Hospital
    • Contact: Ming Feng Tsai, Dr.
  • Taipei, Taiwan
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: Chih-Hsun Lin, Dr.
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Hui-Fu Huang, Dr.
  • Taipei, Taiwan
    • Recruiting
    • Tri-Service General Hospital
    • Contact: Hao-Yu Chiao, Dr.
  • Taipei, Taiwan
    • Recruiting
    • Cathay General Hospital
    • Contact: Chi-Ming Pu, Dr.
  • Taipei, Taiwan
    • Recruiting
    • Shin Kong Wu Ho Su Memorial Hospital
    • Contact: Cha-Chun Chen, Dr.
  • Taoyuan District, Taiwan
    • Recruiting
    • Linkou Chang Gung Memorial Hospital
    • Contact: Jiun-Ting Yeh, Dr.
• United States
  • Florida
    • Miami, Florida, United States, 33165
      • Recruiting
      • Reliant Medical Research
      • Contact: Ramses Vega, Dr.
    • Miami, Florida, United States, 33155
      • Recruiting
      • Bioclinical Research
      • Contact: Rogelio Iglesias, Dr.
    • Miami, Florida, United States, 33135
      • Recruiting
      • A and D Doctor Center
      • Contact: Yordan Orive, Dr.
    • Miami, Florida, United States, 33174-3201
      • Recruiting
      • Advanced Medical Research Institute
      • Contact: Enrique Pelayo, Dr.
    • Palmetto Bay, Florida, United States, 33176
      • Recruiting
      • New Horizons Research
      • Contact: Derrick H. Diaz, Dr.
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Recruiting
      • IACT Health
      • Contact: Joseph Surber, Dr.
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Recruiting
      • The Jackson Clinic PA
      • Contact: Kellie Wallace-Wilding, Dr.
  • Texas
    • Houston, Texas, United States, 77095
      • Recruiting
      • Mt. Olympus Medical Research
      • Contact: Julie Lester, Dr.
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Recruiting
      • Wasatch Clinical Research
      • Contact: Clark Larsen, Dr.
  • Virginia
    • Salem, Virginia, United States, 24153-6404
      • Recruiting
      • Salem Veterans Affairs Medical Center VAMC
      • Contact: Aliza Lee, Dr.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subject must be at least 18 years old.
2. 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.
3. 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.
4. 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.
5. Diabetic foot ulcers should be free of any necrosis or infection
6. Subject has signed the written informed consent form
7. Male subjects must be surgically sterile 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.

8. 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:

1. 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. However, participants who have a history or evidence of osteomyelitis in other parts of their body are eligible to participate in the study. If the medical history of osteomyelitis was cured by antibiotic therapy, surgery or amputation for more than 1 year, and no recurrence, no finding to the current leg and foot after testing, the participant can be enrolled
2. With target ulcer size decreased by at least 30% after at least 2 weeks of standard of care-only period between screening and randomization
3. 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
4. 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
5. Requiring treatment with systemic corticosteroids, immunosuppressive or chemotherapeutic agents
6. With known or suspected hypersensitivity to any ingredients of study product and vehicle
7. With coronary heart disease with myocardial infarction, coronary artery bypass graft, or percutaneous transluminal coronary angioplasty within 3 months prior to study (patients who have undergone peripheral angioplasty should be excluded unless the surgery was performed at least 30 days prior to screening)
8. 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 (within 6 months prior to screening includes both drug abuse and alcohol abuse)
9. History or positive test results for HIV
10. 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
11. Ankle brachial index <0.8 or >1.4
12. Enrollment in any investigational drug trial within 4 weeks before entering this study
13. With any condition judged by the investigator that entering the trial may be detrimental to the subject -

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ENERGI-F703 GEL; ENERGI-F703, topical application, 2 times daily for 16 weeks	Drug: ENERGI-F703 GEL; Standard of care and ENERGI-F703 GEL are applied for the treatment of diabetic foot ulcers.
Placebo Comparator: ENERGI-F703 matched vehicle; ENERGI-F703 matched vehicle, topical application, 2 times daily for 16 weeks	Drug: ENERGI-F703 matched vehicle; Standard of care and ENERGI-F703 matched vehicle are applied for treatment of diabetic foot ulcers.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Energenesis Biomedical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2023
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: June 15, 2023
• First Submitted That Met QC Criteria: June 25, 2023
• First Posted (Actual): July 5, 2023

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; Wound Healing; Diabetic Foot Ulcer
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetic Angiopathies; Diabetes Complications; Skin Diseases; Skin Ulcer; Leg Ulcer; Diabetic Neuropathies; Foot Diseases; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Wounds and Injuries; Diabetes Mellitus; Diabetic Foot; Foot Ulcer
• Other Study ID Numbers: ENERGI-F703-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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