A Novel Injectable Polypeptide Nanoparticle Encapsulated siRNA Targeting TGF-β1 and COX-2 for Localized Fat Reduction II: Phase I Clinical Trial.

[BACKGROUND] Rising demand for non-invasive body contouring is driven by aesthetics and the obesity epidemic. Deoxycholic acid (DCA) is the only FDA-approved injectable for fat reduction but can cause side effects and significant local skin reactions (LSR). RNA interference, using small interfering RNA (siRNA) molecules, offers targeted fat reduction by silencing genes involved in fat maintenance. STP705, a siRNA injectable targeting TGF-β1 and COX-2, has shown promising preclinical results both in vitro and in animal models.

[AIMS] To evaluate the safety and tolerability of STP705 for localized fat reduction in subjects undergoing abdominoplasty.

[METHODS] This phase I dose-ranging, randomized, vehicle-controlled trial involved eight females undergoing abdominoplasty who received subcutaneous STP705 injections at varying concentrations and volumes in designated abdominal zones. Safety assessments, including physical exams, lab tests, ECGs, and local skin reactions (LSRs), were conducted at baseline and follow-ups. Histopathologic evaluations of biopsies collected during abdominoplasty assessed adipocyte apoptosis and tissue remodeling.

[RESULTS] STP705 demonstrated a favorable safety profile with no clinically significant changes in lab values, vital signs, or ECGs. Adverse events (AEs) were rare and transient. The incidence, intensity, and duration of LSRs were low throughout the study. Histological analysis revealed adipocyte destruction, fat remodeling, and necrosis.

[CONCLUSION] STP705 was safe and very well-tolerated and showed preliminary efficacy in inducing adipocyte apoptosis and tissue remodeling, suggesting a safer alternative or adjunct to existing fat reduction therapies. These findings support further trials to establish the safety and efficacy of STP705 for targeted fat reduction and body contouring.

[TRIAL REGISTRATION] ClinicalTrials.gov identifier: NCT05422378.