First-in-human clinical trial evaluating AI-09, a novel long-lasting ready-to-use liquid injectable neuromodulator for the treatment of glabellar lines

Summary: Neuromodulators are used to treat glabellar lines, but most require reconstitution with saline and have a typical duration of 3 to 4 months. A liquid ready-to-use product of longer duration would be preferred by patients. The objectives of this trial were to evaluate the safety, efficacy, and duration of effect of seven ascending dose levels of AI-09 (Eirion Therapeutics). AI-09 is a nanoemulsion formulation of a Type A botulinum holotoxin. 96 participants aged 20-70 were evaluated in this phase I/II, double-blind, vehicle-controlled trial, with moderate to severe glabellar lines. Patients were randomly assigned to receive one of 7 dose strengths of AI-09 (3.5U, 7U, 14U, 28U, 56U, 112U or 224U) or vehicle. Patients received a single treatment at baseline and were followed for 6 months. Efficacy on contraction was evaluated using a 4-point wrinkle scale (Absent, Mild, Moderate, Severe). AI-09 was found to be safe and well tolerated. A dose-response pattern was evident both in terms of efficacy and duration of response. The highest dose tested demonstrated clinically significant efficacy, with an investigator-rated improvement to Absent or Mild wrinkles having a response rate of 87% for active (N=15) vs 7% for vehicle (N=28) at Week 4 (p<0.0001). The median duration of response for this dose was 6 months, with 50% of responders maintaining a response of ≥1 point improvement. Overall, AI-09 and its vehicle were well tolerated. Adverse events were almost all mild or moderate, with only 3 of 38 considered related to the study drug or procedures. There was only one serious adverse event (stroke, 78 days after treatment) and it was not considered related to treatment by the investigator. There was no correlation between dose and frequency of adverse events. The findings of this first-in-man study indicate that injectable AI-09 is an effective and well-tolerated treatment for glabellar lines and offers an appealing alternative for those seeking a ready-to-use and longer-lasting neuromodulator product. Further study of AI-09 is warranted. Monica Boen¹ 1. Cosmetic Laser Dermatology, A Platinum Dermatology Partners Company, San Diego, CA, United States. Clinical Research: Interventional Research