CLEVER Trial – Clesrovimab for prevention of RSV disease in healthy infants

Reference: Zar HJ, Simões EAF, Madhi SA, et al. Clesrovimab for prevention of RSV disease in healthy infants. N Engl J Med. 2025;393(13):1292-1303. Background and Study Rationale Clesrovimab is engineered as a long-acting monoclonal antibody with three amino acid substitutions (YTE modifications) that extend its half-life to approximately 45 days, making single seasonal dosing feasible. Unlike existing RSV antibodies, clesrovimab targets site IV of the RSV fusion protein, which is highly conserved across more than 15,000 RSV sequences with 99.8% identity and is present on both prefusion and postfusion conformations. This binding specificity potentially reduces viral resistance risks compared to other RSV prophylactics. Study Design and Implementation The CLEVER trial employed a robust phase 2b-3, double-blind, randomized, placebo-controlled design across 22 countries, enrolling 3,614 healthy preterm (29-34.6 weeks gestation) and full-term (≥35 weeks) infants entering their first RSV season. The study used 2:1 randomization (clesrovimab: placebo) with stratification by gestational age, chronologic age, and geographic...