The Safety and Pharmacokinetics of the Neutralizing Monoclonal Antibody Bebtelovimab in Pediatric Patients with Mild-to-Moderate COVID-19 to Inform Pandemic Preparedness

Abstract Background Bebtelovimab is a neutralizing monoclonal antibody targeting the SARS-CoV-2 spike protein. Real-world data from 1,690 high-risk adults with COVID-19 showed low progression rates to severe disease after treatment, especially in Omicron subvariant infections. We present its safety and pharmacokinetics (PK) in pediatric patients with mild-to-moderate COVID-19. Methods In the BLAZE-1 trial (NCT04427501), a pediatric-specific, open-label, single-arm protocol enrolled 17 participants aged <12 years or 12–17 years weighing <40 kg. Bebtelovimab was given as a single IV dose using weight-based dosing to match exposure from the adult fixed dose (175 mg) authorized under US FDA emergency-use authorization. Results Of 17 patients, most were aged 2 to <6 years (n=8), followed by 6 to <12 years (n=5); the 0 to <2 and 12 to 17 years (<40 kg) groups had 2 patients each. Mean age was 5.9 ± 4.3 years; 47% were male, 71% African American. Bebtelovimab geometric mean Cmax was 49.1 µg/mL (CV 74.5%), and AUC(0–∞) was 481 µg·day/mL (CV 45.8%). Four participants (24%) had five mild/moderate treatment-emergent adverse events (TEAEs), all resolved by study end. Influenza was most common, treated with oseltamivir and supportive therapies. Constipation was managed with enemas, and elevated creatine phosphokinase required no treatment. No serious adverse events or deaths occurred. Conclusion The PK results support pediatric weight-based dosing, yielding exposures comparable to adult dosing. Safety evaluation identified no new safety signals. These findings provide key benchmark data for pediatric use of neutralizing monoclonal antibodies in future pandemic preparedness. Clinical Trial. Gov identifier NCT04427501