ENERGI-F703 gel, as a new topical treatment for diabetic foot and leg ulcers: A multicenter, randomized, double-blind, phase II trial

Jui-Yung Yang; Cha-Chun Chen; Shun-Cheng Chang; Jiun-Ting Yeh; Hui-Fu Huang; Hwang-Chi Lin; Shang-Hsi Lin; Yu-Hsien Lin; Lin-Gwei Wei; Tom J Liu; Shih-Yuan Hung; Hui-Mei Yang; Hui-Hsiu Chang; Chih-Hsin Wang; Yuan-Sheng Tzeng; Chieh-Huei Huang; Chang-Yi Chou; Ying-Sheng Lin; Shih-Yi Yang; Han-Min Chen; Jiun-Tsai Lin; Yi-Fang Cheng; Guang-Huar Young; Chun-Fang Huang; Ya-Chun Kuo; Niann-Tzyy Dai

doi:10.1016/j.eclinm.2022.101497

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.

Authors

Jui-Yung Yang¹, Cha-Chun Chen², Shun-Cheng Chang³, Jiun-Ting Yeh⁴, Hui-Fu Huang⁵, Hwang-Chi Lin², Shang-Hsi Lin², Yu-Hsien Lin², Lin-Gwei Wei⁶, Tom J Liu⁷, Shih-Yuan Hung⁸, Hui-Mei Yang⁸, Hui-Hsiu Chang⁷, Chih-Hsin Wang⁹, Yuan-Sheng Tzeng⁹, Chieh-Huei Huang⁵, Chang-Yi Chou⁶, Ying-Sheng Lin⁷, Shih-Yi Yang¹, Han-Min Chen¹⁰, Jiun-Tsai Lin¹⁰, Yi-Fang Cheng¹⁰, Guang-Huar Young¹⁰, Chun-Fang Huang¹⁰, Ya-Chun Kuo¹⁰, Niann-Tzyy Dai⁹

Affiliations

¹ Division of General Plastic Surgery, Taipei Chang Gung Memorial Hospital, Taipei, Taiwan.
² Division of Plastic Surgery, Shin Kong Memorial Wu Ho-Su Hospital, Taipei, Taiwan.
³ Division of Plastic Surgery, Shuang Ho Hospital, New Taipei, Taiwan.
⁴ Division of Trauma Plastic Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁵ Division of Plastic Surgery, National Taiwan University Hospital, Taipei, Taiwan.
⁶ Division of Plastic Surgery, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan.
⁷ Division of Plastic Surgery, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan.
⁸ Division of Endocrinology and Metabolism, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁹ Division of Plastic and Reconstructive Surgery, Tri-Service General Hospital, Taipei, Taiwan.
¹⁰ Energenesis Biomedical Co. Ltd, Taipei, Taiwan.

Abstract

Background: Diabetic foot and leg ulcers are a major cause of disability among patients with diabetes mellitus. A topical gel called ENERGI-F703, applied twice daily and with adenine as its active pharmaceutical ingredient, accelerated wound healing in diabetic mice. The current study evaluated the safety and efficacy of ENERGI-F703 for patients with diabetic foot and leg ulcers.

Methods: This randomized, double-blind, multicenter, phase II trial recruited patients from eight medical centers in Taiwan. Patients with intractable diabetic foot and leg ulcers (Wagner Grade 1-3 without active osteomyelitis) were randomly assigned (2:1) to receive topical ENERGI-F703 gel or vehicle gel twice daily for 12 weeks or until complete ulcer closure. The investigator, enrolled patients and site personnel were masked to treatment allocation. Intention to treat (ITT) population and safety population were patient to primary analyses and safety analyses, respectively. Primary outcome was complete ulcer closure rate at the end of treatment. This trial is registered with ClinicalTrials.gov, number NCT02672436.

Findings: Starting from March 15^th, 2017 to December 26^th, 2019, 141 patients were enrolled as safety population and randomized into ENERGI-F703 gel (n = 95) group or vehicle gel (n = 46) group. In ITT population, ENERGI-F703 (n = 90) and vehicle group showed ulcer closure rates of 36.7% (95% CI = 26.75% - 47.49%) and 26.2% (95% CI = 13.86% - 42.04%) with difference of 9.74 % (95 % CI = -6.74% - 26.23%) and 25% quartiles of the time to complete ulcer closure of 69 days and 84 days, respectively. There were 25 (26.3%) patients in ENERGI-F703 group and 11 (23.9%) patients in vehicle group experiencing serious adverse events and five deaths occurred during the study period, none of them related to the treatment.

Interpretation: Our study suggests that ENERGI-F703 gel is a safe and well-tolerated treatment for chronic diabetic foot and leg ulcers. Further studies are needed to corroborate our findings in light of limitations.

Funding: Energenesis Biomedical Co., Ltd.

Keywords: ATP; Adenine; Adenosine triphosphate; Diabetic foot ulcer; Diabetic wound healing.

Associated data

ClinicalTrials.gov/NCT02672436