Efficacy and safety of ziresovir in hospitalised infants aged 6 months or younger with respiratory syncytial virus infection in China: findings from a phase 3 randomised trial with 24-month follow-up

Abstract

Background: Respiratory syncytial virus (RSV) is a particularly dangerous infection in some populations, including very young infants. This study examined the efficacy and safety of ziresovir in hospitalised infants aged 6 months or younger with RSV infection.

Methods: In this double-blind, randomised, placebo-controlled trial conducted across 28 hospitals in China, patients aged 1-24 months hospitalised for virologically confirmed RSV infection were randomly allocated (2:1) to receive ziresovir (10-40 mg by weight twice daily) or placebo orally for 5 days, with 2 years of follow-up. Patients were included if they had a Wang bronchiolitis clinical score (WBCS) of at least 5 at first dosing and were administered their first dose of study drug within 7 days of the onset of symptoms of RSV infection. In this prespecified subanalysis of patients aged 6 months and younger at randomisation, we analysed the primary endpoint (change from baseline in WBCS on day 3 [48 h post-baseline]) in the intention-to-treat infected (ITT-i) population (comprising patients who received at least one dose of study drug and who had PCR-confirmed RSV infection). Safety endpoints were assessed in all patients who received at least one dose. This study is registered with ClinicalTrials.gov (NCT04231968) and is completed.

Findings: Participants were recruited from Sept 22, 2020, to Jan 19, 2022, and followed up to Feb 4, 2024. Among patients aged 6 months or younger, 188 participants (125 in the ziresovir group and 63 in the placebo group) received at least one dose of study drug and were included in the safety analysis, while the ITT-i population included 150 patients (100 in the ziresovir group and 50 in the placebo group). In the ziresovir group, 33 (26%) of 125 patients were female, 92 (74%) were male, mean age was 3·4 months (SD 1·4), and mean baseline WBCS was 6·8 (SD 1·7). In the placebo group, 15 (24%) of 63 patients were female, 48 (76%) were male, mean age was 3·3 months (1·5), and mean baseline WBCS was 6·9 (1·8). The least-squares mean change in WBCS from baseline to day 3 was -3·5 points (95% CI -3·9 to -3·1) with ziresovir versus -2·2 points (-2·8 to -1·7) with placebo (difference -1·2 [95% CI -1·9 to -0·6], p=0·0004). Drug-related treatment-emergent adverse events occurred in 22 (18%) of 125 patients who received ziresovir and seven (11%) of 63 patients who received placebo. No drug-related serious adverse events were observed and no deaths occurred.

Interpretation: Ziresovir had a favourable safety profile and was associated with a significant clinical benefit during the treatment period compared with placebo in patients aged 6 months or younger.

Funding: Shanghai Ark Biopharmaceutical, National Clinical Research Center for Respiratory Diseases, and National Major Science and Technology Projects of China.