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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 (C max ), time to maximum concentration (t max ), and area under the concentration-time curve from time 0 to Day 150 (AUC 0-150 ) 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]) C max was 46.9 (21.7) μg/mL, median (range) t max was 7.0 (4.9, 29.9) days, and geometric mean (%CV) AUC 0-150 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., (© 2024 AstraZeneca and The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

In order to encourage innovative medicine to address Chinese unmet medical needs, China has changed its drug regulatory landscape to speed up access to new medicines. In order to understand the fast-changing landscape and to enable planning of more global drug development programs and study designs in China, we reviewed 15 published clinical pharmacology-related guidances by the National Medical Products Administration (NMPA), and compared them with reference guidances from the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), or the International Conference on Harmonization (ICH), to understand the similarities and differences, especially any China-specific requirements, such as ethnic sensitivity analysis. Overall, by reviewing these clinical pharmacology-related NMPA guidances, it is clear that NMPA guidances are very similar to FDA, EMA, and ICH guidances. There are no relevant differences in the major principles, but some differences in structure, contents, and focus were noted. The NMPA is adapting flexibility statements into newly published guidances. Ethnic sensitivity analysis needs to be implemented early in drug development plans. The NMPA encourages sponsors to conduct early clinical trials in China or include China early in multiregional clinical trials, and to obtain safety, efficacy, and pharmacokinetic data for ethnic sensitivity analysis. Depending on the stage of development, ethnic sensitivity analysis can be conducted using in vitro or literature data, other Asian clinical data, or Chinese clinical data., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)