BACKGROUND: Clesrovimab is an investigational monoclonal antibody with an extended half-life targeting site IV of the respiratory syncytial virus (RSV) fusion protein for the prevention of RSV disease in infants. METHODS: In this phase 1b/2a, double-blind study, 183 healthy preterm and full-term infants 2 weeks to 8 months of age were randomized 4:1 within 5 panels (preterm 20, 50, 75, or 100 mg
full-term 100 mg) to receive 1 dose of clesrovimab or placebo. The objectives were to evaluate safety, pharmacokinetics, serum neutralizing antibodies (SNA), and antidrug antibodies (ADA). The incidence of RSV-associated end points (medically attended lower respiratory tract infection, hospitalization, and acute respiratory infection) were also evaluated through 150 days postdose. RESULTS: The most common adverse event through day 14 was irritability
no treatment-related serious AEs were reported. Clesrovimab serum concentrations displayed a geometric mean apparent half-life of 44.9 days. Of participants receiving clesrovimab, 51 (36.7%) developed ADA with no apparent impact in pharmacokinetics. SNA titers increased in a dose-dependent manner at day 150. The incidences of RSV-associated end points were lower in infants treated with clesrovimab compared with placebo. CONCLUSIONS: Clesrovimab was generally well tolerated and exhibited an extended half-life compared to typical IgG1 antibodies, supporting its ongoing development in late-stage trials. Clinical Trial Registration. NCT03524118.