Benralizumab in children with severe eosinophilic asthma : Pharmacokinetics and long-term safety (TATE study)
© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd..
BACKGROUND: Benralizumab is an anti-interleukin-5 receptor α monoclonal antibody approved as an add-on maintenance treatment for patients with uncontrolled severe asthma. Prior Phase 3 studies have evaluated benralizumab in patients aged ≥12 years with severe uncontrolled asthma. The TATE study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of benralizumab treatment in children.
METHODS: TATE was an open-label, Phase 3 study of benralizumab in children aged 6-11 years from the United States and Japan (plus participants aged 12-14 years from Japan) with severe eosinophilic asthma. Participants received benralizumab 10/30 mg according to weight (<35/≥35 kg). Primary endpoints included maximum serum concentration (Cmax ), clearance, half-life (t1/2 ), and blood eosinophil count. Clearance and t1/2 were derived from a population PK (popPK) analysis. Safety and tolerability were also assessed.
RESULTS: Twenty-eight children aged 6-11 years were included, with an additional two participants from Japan aged 12-14 years also included in the popPK analysis. Mean Cmax was 1901.2 and 3118.7 ng/mL in the 10 mg/<35 kg and 30 mg/≥35 kg groups, respectively. Clearance was 0.257, and mean t1/2 was 14.5 days. Near-complete depletion of blood eosinophils was shown across dose/weight groups. Exploratory efficacy analyses found numerical improvements in mean FEV1 , mean ACQ-IA, patient/clinician global impression of change, and exacerbation rates. Adverse events occurred in 22/28 (78.6%) of participants; none led to discontinuation/death.
CONCLUSION: PK, PD, and safety data support long-term benralizumab in children with severe eosinophilic asthma, and were similar to findings in adolescents and adults.
TRIAL REGISTRATION: ClinicalTrials.gov-ID: NCT04305405.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:35 |
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| Enthalten in: |
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology - 35(2024), 3 vom: 16. März, Seite e14092 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wedner, H James [VerfasserIn] |
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| Links: |
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| Themen: |
71492GE1FX |
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| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 21.03.2024 published: Print ClinicalTrials.gov: NCT04305405 Citation Status MEDLINE |
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| doi: |
10.1111/pai.14092 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM369814754 |
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| 500 | |a Date Revised 21.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT04305405 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. | ||
| 520 | |a BACKGROUND: Benralizumab is an anti-interleukin-5 receptor α monoclonal antibody approved as an add-on maintenance treatment for patients with uncontrolled severe asthma. Prior Phase 3 studies have evaluated benralizumab in patients aged ≥12 years with severe uncontrolled asthma. The TATE study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of benralizumab treatment in children | ||
| 520 | |a METHODS: TATE was an open-label, Phase 3 study of benralizumab in children aged 6-11 years from the United States and Japan (plus participants aged 12-14 years from Japan) with severe eosinophilic asthma. Participants received benralizumab 10/30 mg according to weight (<35/≥35 kg). Primary endpoints included maximum serum concentration (Cmax ), clearance, half-life (t1/2 ), and blood eosinophil count. Clearance and t1/2 were derived from a population PK (popPK) analysis. Safety and tolerability were also assessed | ||
| 520 | |a RESULTS: Twenty-eight children aged 6-11 years were included, with an additional two participants from Japan aged 12-14 years also included in the popPK analysis. Mean Cmax was 1901.2 and 3118.7 ng/mL in the 10 mg/<35 kg and 30 mg/≥35 kg groups, respectively. Clearance was 0.257, and mean t1/2 was 14.5 days. Near-complete depletion of blood eosinophils was shown across dose/weight groups. Exploratory efficacy analyses found numerical improvements in mean FEV1 , mean ACQ-IA, patient/clinician global impression of change, and exacerbation rates. Adverse events occurred in 22/28 (78.6%) of participants; none led to discontinuation/death | ||
| 520 | |a CONCLUSION: PK, PD, and safety data support long-term benralizumab in children with severe eosinophilic asthma, and were similar to findings in adolescents and adults | ||
| 520 | |a TRIAL REGISTRATION: ClinicalTrials.gov-ID: NCT04305405 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a asthma | |
| 650 | 4 | |a eosinophils | |
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| 650 | 4 | |a interleukin-5 | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 4 | |a safety | |
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| 650 | 7 | |a benralizumab |2 NLM | |
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| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
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| 700 | 1 | |a Guilbert, Theresa W |e verfasserin |4 aut | |
| 700 | 1 | |a Ikeda, Masanori |e verfasserin |4 aut | |
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| 700 | 1 | |a Lukka, Pradeep B |e verfasserin |4 aut | |
| 700 | 1 | |a Asimus, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Durżyński, Tomasz |e verfasserin |4 aut | |
| 700 | 1 | |a Johnston, James |e verfasserin |4 aut | |
| 700 | 1 | |a White, Wendy I |e verfasserin |4 aut | |
| 700 | 1 | |a Shah, Mihir |e verfasserin |4 aut | |
| 700 | 1 | |a Werkström, Viktoria |e verfasserin |4 aut | |
| 700 | 1 | |a Jison, Maria L |e verfasserin |4 aut | |
| 700 | 0 | |a all TATE investigators |e verfasserin |4 aut | |
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