- Sekerel BE. Efficacy, safety and pharmacokinetics of ligelizumab: Results from a dedicated Phase 2b study in adolescent patients with chronic spontaneous urticarial. D3T01.1A, EADV Congress 2021, 29 Sept–2 Oct.
An international, randomised, controlled phase 2b study (NCT03437278) investigated the monoclonal anti-IgE antibody ligelizumab that had shown success in adults as a therapeutic agent in adolescents with CSU1. The dose-finding phase 2b trial randomised patients ≥12 and <18 years of age to placebo, 24 mg of ligelizumab or 120 mg of ligelizumab every 4 weeks over 24 weeks and a follow-up until week 40.
Participants in the placebo arm were switched to 120 mg of ligelizumab at week 12. The focus of the trial was on safety, pharmacokinetics, the exposure-response relationship and the efficacy profile. However, with 49 adolescents entering the study, there was no sufficient power to determine differences between treatment arms.
Baseline data included a mean age of 14.8 years, 57.1% women, and a mean bodyweight of 61.0 kg. The participants suffered from CSU for an average of nearly 3 years and had all been refractory to H1-antihistamines. Treatment with 120 mg of ligelizumab was numerically superior to placebo. Moreover, the rate of patients with complete response, equalling a weekly Urticaria Activity Score of 0, was greatest with the higher dose of the active drug and reached 61.5% at week 24.
Predictive modelling of pharmacokinetics demonstrated similarity between adults and adolescents. “After accounting for a bodyweight effect on clearance and other parameters, no additional age effect could be detected,” explained Prof. Bulent Sekerel (Hacettepe University, Turkey). The clearance of ligelizumab was influenced by bodyweight but not by age.
“Ligelizumab was well tolerated and no new safety signals were observed at any dose in the adolescent patients,” Prof. Sekerel pointed out. Overall, 77.6% of patients experienced at least 1 adverse event. Most common were nasopharyngitis and headache. Serious adverse events happened in 2 patients, both were not adjudicated as study drug emergent.
“In conclusion, in this study, ligelizumab exhibited an efficacy profile in adolescent patients with CSU consistent with that known in adults and the similarity in ligelizumab pharmacokinetics and model-estimated potency may support the use of the same dose for treatment for CSU in both adolescents and adults,” Prof. Sekerel summarised. The phase 3 studies PEARL1 (NCT03580356) and PEARL2 (NCT03580369) will further evaluate efficacy and are already underway.