Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection
Shunying Zhao, Yunxiao Shang, Yong Yin, Yingxue Zou, Yongsheng Xu, Li-Li Zhong, Hailin Zhang, Hua Zhang, Deyu Zhao, Tong Shen, Dongming Huang, Qiang Chen, Qiaozhi Yang, Yungang Yang, Xiaoyan Dong, Ling Li, Zhi‐Min Chen, Enmei Liu, Li Deng, Wenhui Jiang, Huanji Cheng, Guangmin Nong, Xiufang Wang, Yiping Chen, Rong Ding, Wei Zhou, Yuejie Zheng, Zhaobo Shen, Xiaoxia Lü, Chuangli Hao, Xiaoping Zhu, Tan Jia, Yan Wu, Gang Zou, Ki Rito, Jim Z. Wu, Hanmin Liu, Xin Ni
Abstract
BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of severe illness in infants, with no effective treatment. Results of a phase 2 trial suggested that ziresovir may have efficacy in the treatment of infants hospitalized with RSV infection. METHODS: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial conducted in China, we enrolled participants 1 to 24 months of age who were hospitalized with RSV infection. Participants were randomly assigned, in a 2:1 ratio, to receive ziresovir (at a dose of 10 to 40 mg, according to body weight) or placebo, administered twice daily, for 5 days. The primary end point was the change from baseline to day 3 (defined as 48 hours after the first administration) in the Wang bronchiolitis clinical score (total scores range from 0 to 12, with higher scores indicating greater severity of signs and symptoms). The intention-to-treat population included all the participants with RSV-confirmed infection who received at least one dose of ziresovir or placebo; the safety population included all the participants who received at least one dose of ziresovir or placebo. RESULTS: copies per milliliter [95% CI, -1.1 to -0.2]). Improvements were observed in prespecified subgroups, including in participants with a baseline bronchiolitis score of at least 8 and in those 6 months of age or younger. The incidence of adverse events related to the drug or placebo was 16% with ziresovir and 13% with placebo. The most common adverse events that were assessed by the investigator as being related to the drug or placebo were diarrhea (in 4% and 2% of the participants, respectively), an elevated liver-enzyme level (in 3% and 3%, respectively), and rash (in 2% and 1%). Resistance-associated mutations were identified in 15 participants (9%) in the ziresovir group. CONCLUSIONS: Ziresovir treatment reduced signs and symptoms of bronchiolitis in infants and young children hospitalized with RSV infection. No safety concerns were identified. (Funded by Shanghai Ark Biopharmaceutical; AIRFLO ClinicalTrials.gov number, NCT04231968.).