Ligelizumab in adolescents with chronic spontaneous urticaria: Results of a dedicated phase 2b randomized clinical trial supported with pharmacometric analysis
Por:
Staubach P, Alvaro-Lozano M, Sekerel BE, Maurer M, Ben-Shoshan M, Porter M, Hua E, Ji Y, Burciu A, Savelieva M, Severin T, Drollmann A and Bienczak A
Publicada:
1 jul 2023
Resumen:
BackgroundChronic spontaneous urticaria (CSU), a long-lasting disease in children, impacts their quality of life. We report the results of a phase 2b dose-finding trial of ligelizumab (NCT03437278) and a high-affinity humanized monoclonal anti-IgE antibody, in adolescents with CSU, supported by modeling and simulation analyses, mitigating challenges in pediatric drug development. MethodsThis multicenter, double-blind, placebo-controlled trial, randomized H1-antihistamine-refractory adolescent CSU patients (12-18 years) 2:1:1 to ligelizumab 24 mg, 120 mg, or placebo every 4 weeks for 24 weeks. Patients on placebo transitioned to ligelizumab 120 mg at week 12. Integrating data from the previous adult and present adolescent trial of ligelizumab, a nonlinear mixed-effects modeling described the longitudinal changes in ligelizumab pharmacokinetics, and its effect on weekly Urticaria Activity Score (UAS7). ResultsBaseline UAS7 (mean & PLUSMN; SD) was 30.5 & PLUSMN; 7.3 (n = 24), 29.3 & PLUSMN; 7.7 (n = 13), and 32.5 & PLUSMN; 9.0 (n = 12) for patients (median age, 15 years) on ligelizumab 24 mg, 120 mg, and placebo, respectively. Change from baseline in UAS7 at week 12 with ligelizumab 24 mg, 120 mg, and placebo was -15.7 & PLUSMN; 10.9, -18.4 & PLUSMN; 12.3, and -13.0 & PLUSMN; 13.0, respectively. Ligelizumab was well-tolerated. The modeling analysis showed that body weight, but not age, affected ligelizumab's apparent clearance. No significant differences between adolescents and adults were detected on the model-estimated maximum effect and potency. ConclusionsLigelizumab exhibited efficacy and safety in adolescent CSU patients, consistent with that in adults. The PK and potency of ligelizumab were not impacted by age, and the same dose of ligelizumab can be used for treating adolescents and adults with CSU. Our study shows how modeling and simulation can complement pediatric drug development.
Filiaciones:
Staubach P:
Department of Dermatology, University Medical Center, Mainz, Germany
Alvaro-Lozano M:
Department of Pediatric Allergology and Clinical Immunology, Hospital Sant Joan de Déu, Esplugues (Barcelona), Institut de Recerca Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain
Sekerel BE:
Faculty of Medicine, Pediatric Allergy and Asthma Unit, Hacettepe University, Ankara, Turkey
Maurer M:
Institute of Allergology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany
Ben-Shoshan M:
Division of Allergy and Clinical Immunology, Department of Paediatrics, Montreal Children's Hospital McGill University Health Centre, Montreal, Quebec, Canada
Porter M:
Novartis Pharma AG, Basel, Switzerland
Hua E:
Shanghai Novartis Trading Ltd., Shanghai, China
Ji Y:
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA
Burciu A:
Novartis Pharma AG, Basel, Switzerland
Savelieva M:
Novartis Pharma AG, Basel, Switzerland
Severin T:
Novartis Pharma AG, Basel, Switzerland
Drollmann A:
Novartis Pharma AG, Basel, Switzerland
Bienczak A:
Novartis Pharma AG, Basel, Switzerland
Bronze
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