Efficacy and Safety of N‐Acetyl‐GED‐0507‐34‐LEVO Gel in Patients with Moderate‐to Severe Facial Acne Vulgaris: A Phase 2B randomised double‐blind, vehicle‐controlled trial

Preliminary in vitro and in vivo studies have supported the efficacy of the peroxisome proliferator-activated receptor-γ (PPARγ) modulator N-Acetyl-GED-0507-34-LEVO (NAC-GED) for the treatment of acne inducing sebocyte differentiation, improving sebum composition and controlling the inflammatory process.Evaluation of the efficacy and safety of NAC-GED (5% and 2%) in subjects with moderate-to- severe facial acne vulgaris.This double-blind, phase 2 randomized controlled clinical trial was conducted at 36 sites in Germany, Italy, and Poland. Facial acne patients, aged 12-30 years, with an Investigator's Global Assessment (IGA) score of 3-4 and an inflammatory and non-inflammatory lesion count of 20-100 were randomized to topically apply the study drug (2% or 5%) or placebo (vehicle), once daily for 12 weeks. The efficacy co-primary endpoints were percentage change from baseline in total lesion count (TLC) and IGA success at week 12; the safety endpoints were adverse and serious tolerability adverse events (AE and SAE). This study was registered with EudraCT, 2018-003307-19.Between Q1, 2019 and Q1, 2020 450 patients [418 (93%) with IGA=3; 32 (7%) with IGA=4] were randomly assigned to NAC-GED 5%, NAC-GED 2% or vehicle (n=150 each). The percent change TLC reduction was significantly higher in both the NAC-GED 5% (-57.1%, 95% CI: -60.8,- 53.4, p<0.001) and 2% (-44.7%, 95% CI:-49.1,-40.1, p<0.001) groups compared to vehicle (-%, 95% CI: -37.6,-30.2). A higher proportion of patients treated with NAC-GED 5% experienced IGA success (45%, 95% CI:38,53) compared to the vehicle group (24%, 95% CI:18,31), p<0.001. IGA success rate was 33% in NAC-GED 2% group (p=n.s vs vehicle). The percentage of patients who had ≥ 1AEs was 19%, 16%, and 19% (NAC-GED 5%, NAC-GED 2% and vehicle, respectively).The topical application of NAC-GED 5% reduced TLC, increased the IGA success rate and was safe for patients with acne vulgaris. Thus, NAC-GED, a new PPARγ modulator, showed an effective clinical response.