A phase I, randomized, placebo‐controlled trial to evaluate the pharmacokinetics, safety, and tolerability of nirsevimab in healthy Chinese adults
Abstract Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) in infants worldwide. Nirsevimab, an extended half‐life monoclonal antibody against RSV, is approved in China for the prevention of RSV lower respiratory tract disease in infants; however, glo...
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| Language: | English |
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Wiley
2025-01-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.70095 |
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| author | Xiaomeng Mao Xiaohan Hua Chengyi Wu Xiaoyun Ge Jie Zhang Xiaojie Wu Robert J. Kubiak Ulrika Wählby Hamrén Tonya Villafana Georgios Christou Jannine Green Therese Takas Yuwen Jin |
| author_facet | Xiaomeng Mao Xiaohan Hua Chengyi Wu Xiaoyun Ge Jie Zhang Xiaojie Wu Robert J. Kubiak Ulrika Wählby Hamrén Tonya Villafana Georgios Christou Jannine Green Therese Takas Yuwen Jin |
| author_sort | Xiaomeng Mao |
| collection | DOAJ |
| description | Abstract Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) in infants worldwide. Nirsevimab, an extended half‐life monoclonal antibody against RSV, is approved in China for the prevention of RSV lower respiratory tract disease in infants; however, global nirsevimab trials did not enroll Chinese infants. To inform the investigation of nirsevimab for the prevention of RSV LRTI in Chinese infants, this Phase I, randomized, placebo‐controlled trial evaluated the pharmacokinetics (PK) and safety of nirsevimab in healthy Chinese adults. Participants were randomized 3:1 to a single 300 mg intramuscular dose of nirsevimab or placebo and were followed through 150 days post‐dose. Serum nirsevimab concentrations were measured and PK parameters of maximum serum concentration (Cmax), time to maximum concentration (tmax), and area under the concentration‐time curve from time 0 to Day 150 (AUC0–150) were estimated. Treatment emergent adverse events (AEs), clinical laboratory data, and vital signs were evaluated. Overall, 24 participants were randomized to nirsevimab (n = 18) or placebo (n = 6). Nirsevimab geometric mean (coefficient of variation [%CV]) Cmax was 46.9 (21.7) μg/mL, median (range) tmax was 7.0 (4.9, 29.9) days, and geometric mean (%CV) AUC0–150 was 4210.6 (13.6) μg·day/mL. Treatment‐emergent AEs (all Grade 1 or Grade 2 in severity) were reported in 5/18 (27.8%) nirsevimab recipients and 2/6 (33.3%) placebo recipients. No serious AEs, new onset chronic disease, or deaths were reported. Overall, safety and PK outcomes were consistent with those observed in healthy adults in the USA, with no new safety concerns. |
| format | Article |
| id | doaj-art-972c0e554c4545ea83401044b188263c |
| institution | Kabale University |
| issn | 1752-8054 1752-8062 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj-art-972c0e554c4545ea83401044b188263c2025-01-24T08:17:46ZengWileyClinical and Translational Science1752-80541752-80622025-01-01181n/an/a10.1111/cts.70095A phase I, randomized, placebo‐controlled trial to evaluate the pharmacokinetics, safety, and tolerability of nirsevimab in healthy Chinese adultsXiaomeng Mao0Xiaohan Hua1Chengyi Wu2Xiaoyun Ge3Jie Zhang4Xiaojie Wu5Robert J. Kubiak6Ulrika Wählby Hamrén7Tonya Villafana8Georgios Christou9Jannine Green10Therese Takas11Yuwen Jin12Clinical Pharmacology Research Center, Huashan Hospital Fudan University Shanghai ChinaClinical Development, Respiratory & Immunology, R&D China AstraZeneca Shanghai ChinaBiometrics, R&D China AstraZeneca Shanghai ChinaClinical Safety, R&D China AstraZeneca Shanghai ChinaDevelopment Operations, R&D China AstraZeneca Shanghai ChinaClinical Pharmacology Research Center, Huashan Hospital Fudan University Shanghai ChinaClinical Pharmacology and Quantitative Pharmacology, R&D AstraZeneca Gaithersburg Maryland USAClinical Pharmacology and Quantitative Pharmacology, R&D AstraZeneca Gothenburg SwedenClinical Development, Vaccines and Immune Therapies, Biopharmaceuticals R&D AstraZeneca Gaithersburg Maryland USAPatient Safety, Chief Medical Office, R&D AstraZeneca Gaithersburg Maryland USAGlobal Clinical Operations, R&D AstraZeneca Macclesfield UKClinical Development, Vaccines and Immune Therapies, Biopharmaceuticals R&D AstraZeneca Gaithersburg Maryland USAClinical Pharmacology, R&D China AstraZeneca Shanghai ChinaAbstract Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) in infants worldwide. Nirsevimab, an extended half‐life monoclonal antibody against RSV, is approved in China for the prevention of RSV lower respiratory tract disease in infants; however, global nirsevimab trials did not enroll Chinese infants. To inform the investigation of nirsevimab for the prevention of RSV LRTI in Chinese infants, this Phase I, randomized, placebo‐controlled trial evaluated the pharmacokinetics (PK) and safety of nirsevimab in healthy Chinese adults. Participants were randomized 3:1 to a single 300 mg intramuscular dose of nirsevimab or placebo and were followed through 150 days post‐dose. Serum nirsevimab concentrations were measured and PK parameters of maximum serum concentration (Cmax), time to maximum concentration (tmax), and area under the concentration‐time curve from time 0 to Day 150 (AUC0–150) were estimated. Treatment emergent adverse events (AEs), clinical laboratory data, and vital signs were evaluated. Overall, 24 participants were randomized to nirsevimab (n = 18) or placebo (n = 6). Nirsevimab geometric mean (coefficient of variation [%CV]) Cmax was 46.9 (21.7) μg/mL, median (range) tmax was 7.0 (4.9, 29.9) days, and geometric mean (%CV) AUC0–150 was 4210.6 (13.6) μg·day/mL. Treatment‐emergent AEs (all Grade 1 or Grade 2 in severity) were reported in 5/18 (27.8%) nirsevimab recipients and 2/6 (33.3%) placebo recipients. No serious AEs, new onset chronic disease, or deaths were reported. Overall, safety and PK outcomes were consistent with those observed in healthy adults in the USA, with no new safety concerns.https://doi.org/10.1111/cts.70095 |
| spellingShingle | Xiaomeng Mao Xiaohan Hua Chengyi Wu Xiaoyun Ge Jie Zhang Xiaojie Wu Robert J. Kubiak Ulrika Wählby Hamrén Tonya Villafana Georgios Christou Jannine Green Therese Takas Yuwen Jin A phase I, randomized, placebo‐controlled trial to evaluate the pharmacokinetics, safety, and tolerability of nirsevimab in healthy Chinese adults Clinical and Translational Science |
| title | A phase I, randomized, placebo‐controlled trial to evaluate the pharmacokinetics, safety, and tolerability of nirsevimab in healthy Chinese adults |
| title_full | A phase I, randomized, placebo‐controlled trial to evaluate the pharmacokinetics, safety, and tolerability of nirsevimab in healthy Chinese adults |
| title_fullStr | A phase I, randomized, placebo‐controlled trial to evaluate the pharmacokinetics, safety, and tolerability of nirsevimab in healthy Chinese adults |
| title_full_unstemmed | A phase I, randomized, placebo‐controlled trial to evaluate the pharmacokinetics, safety, and tolerability of nirsevimab in healthy Chinese adults |
| title_short | A phase I, randomized, placebo‐controlled trial to evaluate the pharmacokinetics, safety, and tolerability of nirsevimab in healthy Chinese adults |
| title_sort | phase i randomized placebo controlled trial to evaluate the pharmacokinetics safety and tolerability of nirsevimab in healthy chinese adults |
| url | https://doi.org/10.1111/cts.70095 |
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