ENERGI-F703 for Diabetic Foot Ulcers Phase II Study

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

The objective of this study is to evaluate the efficacy and safety of ENERGI-F703 in subject with diabetic foot ulcers.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Diabetic Foot; Foot Ulcer; Wounds
• Intervention / Treatment: Drug: ENERGI-F703; Drug: ENERGI-F703 matched vehicle

• Study Type: Interventional
• Enrollment (Actual): 141
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Tri-Service General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. With either gender aged at least 20 years old
2. With diagnosed diabetic mellitus (DM), e.g. currently under DM medication treatment or naïve DM subject with duplicated HbA1c over 6.5% and fasting plasma glucose over 126 mg/dL measured at least one week apart before Screening)
3. With at least one cutaneous ulcer on the foot (including ulcers on the lower legs) and not healing for at least 4 weeks. The largest diabetic foot ulcer will be selected as target ulcer. If two or more ulcers have the largest size, the one with worst grade will be selected. If two 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 3 ulcer according to Wagner Grading System and with ulcer size of 1 cm2 to 36 cm2 (Grade 3 ulcer subject may enter the study only if after debridement, the abscess of target ulcer is under control at investigator's discretion and osteomyelitis does not present)
5. Diabetic foot ulcers should be free of any necrosis or infection in any soft tissue and bone tissue;
6. Subject has signed the written informed consent form

Exclusion Criteria:

1. With active osteomyelitis
2. With target ulcer size decreased by at least 30% after at least 2 weeks of standard-of-care-only period or any other recorded regular therapy either before Screening visit or after completing Initial Phase
3. With poor nutritional status (albumin < 2g/dl), poor diabetic control (HbA1c > 12%), a leukocyte counts < 2,000/mm3, abnormal liver function (AST, ALT>3 x upper limit of normal range) within 14 days before Screening visit or 28 days before Randomization visit Note: HbA1c: hemoglobin A1c; AST: aspartate aminotransferase; ALT: alanine aminotransferase
4. Requiring treatment with systemic corticosteroids, immunosuppressive or chemotherapeutic agents
5. With known or suspected hypersensitivity to any ingredients of study product and vehicle
6. With coronary heart disease with myocardial infarction, coronary artery bypass graft (CABG), or percutaneous transluminal coronary angioplasty (PTCA) within 3 months prior to study
7. Pregnant or lactating or premenopausal with childbearing potential but not taking reliable contraceptive method(s) during the study period Note: Women with childbearing potential should agree to use a highly effective method of birth control, defined as those, alone or in combination, that result in a low failure rate when used consistently and correctly.

8. With the following conditions:

   1. ankle brachial index (ABI) < 0.4 OR
   2. ABI between 0.4 and 0.6 (inclusive) and not received appropriate treatment for improving venous and arterial insufficiency Note: Subjects with ABI between 0.4 and 0.6 (inclusive) and having received appropriate surgical or endovenous/endovascular therapy for improving venous and arterial insufficiency considered by investigators such as valvuloplasty, angioplasty, or bypass grafting will be eligible to enter the study at investigator's discretion.
9. Enrollment in any investigational drug trial within 4 weeks before entering this study
10. 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; ENERGI-F703, topical application, 2 times daily for 12 weeks	Drug: ENERGI-F703; Standard of care and ENERGI-F703 are applied for treatment of diabetic foot ulcers.
Placebo Comparator: Placebo; ENERGI-F703 matched vehicle, topical application, 2 times daily for 12 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 closure rate	Defined as the proportion of subjects with complete ulcer closure at the end of treatment period	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The accumulated confirmed ulcer closure rate at each of the post-treatment visit		Week 1, 2, 4 ,6 ,8, 10, 12
The ulcer closure time	Defined as the time to complete ulcer closure	Week 1, 2, 4, 6, 8, 10, 12
Percentage change in ulcer size for each post-treatment visit	Calculated as (Ulcer size at post treatment visit - Ulcer size at baseline)/(Ulcer size at baseline)	Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24
Adverse event incidence		Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24

Collaborators and Investigators

• Sponsor: Energenesis Biomedical Co., Ltd.
• Collaborators: A2 Healthcare Taiwan Corporation

Publications and helpful links

General Publications

• Yang JY, Chen CC, Chang SC, Yeh JT, Huang HF, Lin HC, Lin SH, Lin YH, Wei LG, Liu TJ, Hung SY, Yang HM, Chang HH, Wang CH, Tzeng YS, Huang CH, Chou CY, Lin YS, Yang SY, Chen HM, Lin JT, Cheng YF, Young GH, Huang CF, Kuo YC, Dai NT. ENERGI-F703 gel, as a new topical treatment for diabetic foot and leg ulcers: A multicenter, randomized, double-blind, phase II trial. EClinicalMedicine. 2022 Jul 10;51:101497. doi: 10.1016/j.eclinm.2022.101497. eCollection 2022 Sep.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2017
• Primary Completion (Actual): October 3, 2019
• Study Completion (Actual): December 26, 2019

Study Registration Dates

• First Submitted: January 27, 2016
• First Submitted That Met QC Criteria: February 1, 2016
• First Posted (Estimate): February 3, 2016

Study Record Updates

• Last Update Posted (Actual): November 24, 2020
• Last Update Submitted That Met QC Criteria: November 23, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; Wound Healing; Diabetic Foot Ulcer
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetic Neuropathies; Foot Diseases; Diabetes Mellitus; Diabetic Foot; Foot Ulcer; Ulcer
• Other Study ID Numbers: ENERGI-F703-01

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