A Phase 1/2a Clinical Trial to Evaluate the Efficacy and Safety of Allogenic Adipose Tissue-Derived Mesenchymal Stem Cell Clusters in Patients with Critical Limb Ischemia.

Abstract

Critical limb ischemia (CLI) is a severe manifestation of peripheral arterial disease, often resulting in ischemic rest pain, non-healing ulcers, or gangrene. Due to the limited effectiveness of conventional revascularization techniques in 5%∼20% of patients, alternative therapeutic approaches are needed. This Phase 1/2a clinical trial evaluated the safety, tolerability, and efficacy of allogeneic adipose tissue-derived mesenchymal stem cell clusters (ADMSCCs) in patients with CLI who were not eligible for standard revascularization methods. The study was conducted in two phases: Phase 1 used a 3＋3 dose-escalation design to determine tolerability, and Phase 2a assessed efficacy at the maximum tolerated dose. Twenty patients were treated with ADMSCCs, with safety (adverse events and dose-limiting toxicity) and efficacy (pain intensity, walking distance, and ulcer size) as primary endpoints. ADMSCCs were injected intramuscularly, and patients were monitored for 24 weeks. ADMSCCs were well-tolerated, with no serious adverse events or dose-limiting toxicities observed. Significant reductions in ischemic pain and increases in pain-free walking distance were noted at 4, 12, and 24 weeks. Although ankle-brachial index and toe-brachial index showed no significant changes, ulcer healing was observed in one participant. These findings suggest that ADMSCC therapy may be a viable alternative for patients with CLI, with a favorable safety profile and sustained therapeutic effects. Further studies with larger sample sizes and randomized control groups are needed to confirm these results and explore integration with existing treatments.