Ligelizumab in adolescents with chronic spontaneous urticaria : Results of a dedicated phase 2b randomized clinical trial supported with pharmacometric analysis
© 2023 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd..
BACKGROUND: Chronic 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.
METHODS: This 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).
RESULTS: Baseline UAS7 (mean ± SD) was 30.5 ± 7.3 (n = 24), 29.3 ± 7.7 (n = 13), and 32.5 ± 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 ± 10.9, -18.4 ± 12.3, and -13.0 ± 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.
CONCLUSIONS: Ligelizumab 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
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| Enthalten in: |
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology - 34(2023), 7 vom: 01. Juli, Seite e13982 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Staubach, Petra [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.07.2023 Date Revised 27.07.2023 published: Print ClinicalTrials.gov: NCT03437278 Citation Status MEDLINE |
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| doi: |
10.1111/pai.13982 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a Date Revised 27.07.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT03437278 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd. | ||
| 520 | |a BACKGROUND: Chronic 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 | ||
| 520 | |a METHODS: This 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) | ||
| 520 | |a RESULTS: Baseline UAS7 (mean ± SD) was 30.5 ± 7.3 (n = 24), 29.3 ± 7.7 (n = 13), and 32.5 ± 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 ± 10.9, -18.4 ± 12.3, and -13.0 ± 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 | ||
| 520 | |a CONCLUSIONS: Ligelizumab 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 | ||
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| 700 | 1 | |a Maurer, Marcus |e verfasserin |4 aut | |
| 700 | 1 | |a Ben-Shoshan, Moshe |e verfasserin |4 aut | |
| 700 | 1 | |a Porter, Miriam |e verfasserin |4 aut | |
| 700 | 1 | |a Hua, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Burciu, Alis |e verfasserin |4 aut | |
| 700 | 1 | |a Savelieva, Marina |e verfasserin |4 aut | |
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| 700 | 1 | |a Drollmann, Anton |e verfasserin |4 aut | |
| 700 | 1 | |a Bienczak, Andrzej |e verfasserin |4 aut | |
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