Peer-reviewed article

Clesrovimab in Infants at Increased Risk For Severe Disease During 2 RSV Seasons: A Randomized Clinical Trial.

Zar HJ, Bont LJ, Manzoni P, Muñoz FM, Ramilo O et al. · 1 Sept 2026

Abstract

Importance Clesrovimab is a long-acting monoclonal antibody approved for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants who are born during or entering their first RSV season; data concerning clesrovimab from a second RSV season among children who remain at risk for severe disease are needed. Objective To evaluate the safety and tolerability of clesrovimab (105 mg) vs palivizumab in RSV season 1 in infants at increased risk for severe RSV disease. Key secondary objectives include describing the safety of 210 mg of clesrovimab in RSV season 2 in children who remain at increased risk for severe RSV disease, clesrovimab pharmacokinetics, and the incidence of RSV-associated disease. Design, setting, and participants SMART (MK-1654-007) was a randomized, partially masked, palivizumab-controlled, phase 3 clinical trial, conducted at 110 sites in 27 countries and territories between November 30, 2021, and November 20, 2025. The population constituted palivizumab-eligible infants, including those with prematurity, chronic lung disease of prematurity, or hemodynamically significant congenital heart disease. Interventions Participants, randomized 1:1 and stratified by region and condition, received clesrovimab (105 mg) on day 1 followed by placebo on day 28 or monthly palivizumab (15 mg/kg) up to 5 doses (1 dose per month). Eligible infants received open-label clesrovimab (210 mg) before their second RSV season. Main outcomes and measures The primary outcome was the observed proportions of participants experiencing adverse events (AEs) after clesrovimab or palivizumab in season 1. Results Overall, 997 infants (500 [50.2%] male; median age, 2.6 [range, 0.0-12.0] months) received clesrovimab, 105 mg (n = 498) or palivizumab (n = 499) in season 1; 276 received clesrovimab, 210 mg open-label in season 2. In season 1, the proportions of participants experiencing AEs were comparable between treatment groups. In season 2, clesrovimab, 210 mg was well tolerated. Incidence rates of RSV-associated medically attended lower respiratory infection (MALRI) were comparable between clesrovimab and palivizumab (3.2% [95% CI, 1.8%-5.2%] and 3.4% [95% CI, 2.0%-5.6%], respectively) through day 150 in season 1; total RSV-associated MALRI incidence through day 180 after a 210-mg dose in season 2 was 7.3% (95% CI, 4.4%-11.4%). Conclusions and relevance In this randomized clinical trial, clesrovimab was well tolerated in infants at increased risk for severe RSV disease through 2 RSV seasons. These findings support the use of clesrovimab in children who remain at risk for severe RSV disease in their second RSV season. Trial registration ClinicalTrials.gov Identifier: NCT04938830.