P-520. Clesrovimab Efficacy through 6 Months during a Time of Changing SARS-CoV-2 Nonpharmaceutical Interventions (NPIs): Subgroup Analysis of the China Cohort in the Phase 2b/3 CLEVER Trial

Abstract Background Clesrovimab, an investigational long-acting monoclonal antibody, reduced the incidence of respiratory syncytial virus (RSV)–associated disease in healthy infants compared with placebo in the phase 2b/3 CLEVER trial (MK-1654-004; NCT04767373). The global trial was conducted during the COVID-19 pandemic when NPIs were widely implemented, disrupting RSV epidemiology and seasonality. In China, RSV cases were low from Jun 2022 to Feb 2023, a period overlapping with trial enrolment and follow-up, constraining the ability to demonstrate the protective effect of clesrovimab. This analysis evaluates the efficacy of clesrovimab within the context of implementation of NPIs in China during the CLEVER trial.Figure 1. Kaplan-Meier analysis of time and number of events from dosing to first RSV-associated outpatient or inpatient MALRI from Day 1 through Day 180 in China Methods Healthy preterm and full-term infants ≤ 1 year old entering their first RSV season were randomized 2:1 to receive 1 intramuscular dose of clesrovimab 105 mg or placebo. RSV-associated medically attended lower respiratory infection (MALRI), requiring ≥ 1 indicator of lower respiratory infection/severity, was assessed through days 150 and 180 post dose during a period of changing SARS-CoV-2 NPIs. Analyses of the China subpopulation followed the overall study methodology of the CLEVER trial. Results In China, enrolment spanned from Aug 20 to Dec 26, 2022, with the last Day 180 follow-up on June 24, 2023. Over 30 study sites, 443 participants received study intervention (clesrovimab, n = 291; placebo, n = 152). Participant disposition was generally comparable between intervention groups. Administration of clesrovimab reduced the incidence of RSV-associated MALRI (outpatient and inpatient) compared with placebo, with an observed efficacy of 89.6% (95% CI, 11.0%-98.8%) and 80.6% (95% CI, 27.3%-94.8%) through Days 150 and 180 post dose, respectively. RSV-associated MALRI cases were low or absent in both groups from Days 1-120 post dose (Dec 2022–Apr 2023) but began to increase following the easing of NPI, starting from Jan 2023, with a higher incidence observed in the placebo versus clesrovimab group from days 140-180 post dose (7 vs 2 cases; Figure 1). Conclusion In China, clesrovimab provided sustained protection against RSV-associated MALRI beyond Day 150 through Day 180 post dose, particularly beyond Day 140, when the majority of cases began to emerge following the easing of NPIs. Disclosures Mingfen Zhu, MSc, MSD, China: Employment Fang Sun, MD, Merck & Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company)|MSD, China: Employment Rui Wang, MSc, MSD, China: Employment Derong Liu, PhD, MSD, China: Employment Chang Chen, PhD, MSD, China: Employment Rong Fu, PhD, MSD, China: Employment Jiahuang Lin, PhD, MSD, China: Employment Yuanqiu Li, PhD, MSD, China: Employment Qiong Shou, PhD, MSD, China: Employment Andrea Guerra, MBBS, MSD (UK) Limited, London, UK: Employment Ying Zhang, PhD, Merck & Co., Inc., Rahway, NJ, USA: Employment|Merck & Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company) Radha A. Railkar, PhD, Merck & Co., Inc., Rahway, NJ, USA: Employment|Merck & Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company) Anushua Sinha, MD, Merck & Co., Inc., Rahway, NJ, USA: Employment|Merck & Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company) Xueyan Liao, PhD, Merck & Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company)|MSD, China: Employment