Randomized Phase 2b Trial of CBL-514 Injection for Abdominal Subcutaneous Fat Reduction With Clinician- and Patient-reported Outcomes and MRI Assessment.

Abstract

CBL-514, a small-molecule injectable lipolysis agent that induces adipocyte apoptosis, demonstrated clinically meaningful reductions in abdominal subcutaneous fat by ultrasound in previous Phase 2 studies, with no observed necrosis or nerve injury. To evaluate the efficacy and safety of CBL-514 for abdominal subcutaneous fat reduction using clinician-reported scale, patient-reported scale, and MRI assessments. In this randomized, single-blind, placebo-controlled Phase 2b trial (NCT05736107), 108 adults with moderate (Grade 3) to severe (Grade 4) abdominal subcutaneous fat were randomized 1:1 to receive up to four CBL-514 (2 mg/cm2; ≤600 mg/treatment) or placebo treatments at 3-week intervals). Primary efficacy was the proportion of participants with ≥1-grade improvement on the Clinician-Reported Abdominal Fat Rating Scale (CR-AFRS) at 12-week follow-up. Secondary endpoints included Patient-Reported AFRS (PR-AFRS), MRI-assessed changes in abdominal fat volume and thickness, and safety. In the full analysis set, 76.7% (23/30) of CBL-514-treated participants achieved ≥1-grade CR-AFRS improvement versus 18.9% (7/37) with placebo (P<0.0001). PR-AFRS results were similar, with 76.7% (23/30) of CBL-514 participants achieving ≥1-grade improvement versus 19.4% (7/36) in placebo (P<0.0001). MRI demonstrated least squares (LS) mean abdominal fat volume reduction compared to baseline of -152.9 mL ± 17.75, with LS mean percent changes of -20.3%, both significantly greater than placebo (P<0.0001). Most responders demonstrated improvement on the CR-AFRS after 1-2 treatments. CBL-514 was well tolerated, with mainly mild, transient injection-site reactions. CBL-514 significantly reduced abdominal fat by patient- and clinician-reported outcomes and MRI, with a favorable safety profile supporting its potential as a minimally invasive option.