Related Experiment Video
Updated: Jan 12, 2026
Prospective, Randomized, and Controlled Study of a Human Umbilical Cord Mesenchymal Stem Cell Injection for Treating Diabetic Foot Ulcers
Published on: March 3, 2023
Anatomically Directed Lower Extremity Gene Therapy for Ulcer Healing: A Double-Blind, Randomized, Placebo-Controlled
David G Armstrong1, Michael S Conte2, Joseph L Mills3
1Department of Surgery, Keck School of Medicine of the University of Southern California, Los Angeles (D.G.A.).
Background:
People with chronic limb-threatening ischemia lack Food and Drug Administration-approved therapies for wound healing, creating an unmet need for novel approaches. Prior studies of biologics in chronic limb-threatening ischemia have largely targeted end-stage patients with amputation-free survival as the primary outcome. This trial evaluated the efficacy of intramuscular administration of AMG0001, a plasmid encoding human HGF (hepatocyte growth factor), to promote ulcer healing in patients with chronic limb-threatening ischemia and neuroischemic ulcers.
Methods:
LEGenD-1 was a double-blind, randomized, placebo-controlled phase II trial conducted at 22 US sites. Seventy-five participants with neuroischemic ulcers and toe pressure or transcutaneous oxygen pressure between 30 and 59 mm Hg were randomized to receive AMG0001 at 4 mg, 8 mg, or placebo. Injections were administered intramuscularly along an angiographically guided target artery path on days 0, 28, 56, and 84. The 2 coprimary end points were time to complete healing and the proportion of subjects with ulcers healed by 6 months in a pooled AMG0001 analysis. Secondary end points included healing by 12 months, ulcer recurrence, and hemodynamic changes.
Results:
Baseline characteristics were comparable across groups (mean age 62.6 years; 80.0% male; 70.7% with diabetes). Mean toe pressure was 46.1 mm Hg, and transcutaneous oxygen pressure was 49.8 mm Hg. Median time to healing was significantly shorter with AMG0001 versus placebo (84 versus 280 days; P=0.007); 4 mg: 98 days (P=0.017); 8 mg: 84 days (P=0.022). By 6 months, 63.3% of AMG0001-treated participants healed versus 38.5% of placebo (P=0.053). By 12 months, healing rates were 77.6% versus 46.2% (P=0.010). Adverse events were similar across groups.
Conclusions:
Anatomically targeted intramuscular delivery of AMG0001 significantly accelerated healing in patients with moderate chronic limb-threatening ischemia and neuroischemic ulcers and may represent a promising nonsurgical therapeutic strategy.
Registration:
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04267640.
Insights
AMG0001, a novel therapy for chronic limb-threatening ischemia, significantly accelerated wound healing in patients with neuroischemic ulcers. This approach offers a promising nonsurgical option for this underserved patient population.
Area of Science:
- Vascular Medicine
- Regenerative Medicine
- Clinical Trials
Background:
- Chronic limb-threatening ischemia (CLTI) lacks FDA-approved therapies for wound healing, presenting a significant unmet medical need.
- Existing biologic studies in CLTI often focus on end-stage patients with amputation-free survival as the primary outcome.
- This trial investigated AMG0001, a plasmid encoding hepatocyte growth factor (HGF), for promoting ulcer healing in CLTI patients.
Purpose of the Study:
- To evaluate the efficacy of intramuscular AMG0001 in promoting ulcer healing in patients with CLTI and neuroischemic ulcers.
- To assess the safety and effectiveness of AMG0001 compared to placebo.
- To determine the optimal dosage and timing for AMG0001 administration.
Main Methods:
- The LEGenD-1 trial was a double-blind, randomized, placebo-controlled Phase II study at 22 US sites.
- Seventy-five participants with neuroischemic ulcers and specific perfusion criteria were randomized to AMG0001 (4 mg or 8 mg) or placebo.
- Intramuscular injections were administered along a guided artery path on days 0, 28, 56, and 84.
Main Results:
- Median time to complete ulcer healing was significantly shorter with AMG0001 versus placebo (84 vs. 280 days; P=0.007).
- By 6 months, 63.3% of AMG0001-treated participants achieved healing compared to 38.5% with placebo (P=0.053).
- Healing rates at 12 months were 77.6% for AMG0001 versus 46.2% for placebo (P=0.010), with similar adverse events across groups.
Conclusions:
- Anatomically targeted intramuscular delivery of AMG0001 significantly accelerated healing in patients with moderate CLTI and neuroischemic ulcers.
- AMG0001 represents a promising nonsurgical therapeutic strategy for CLTI-related wound healing.
- Further investigation into AMG0001 could lead to new treatment options for patients with CLTI.
