Population Pharmacokinetics of Clesrovimab in Preterm and Full‐Term Infants

Clesrovimab is a half-life extended monoclonal antibody targeting the respiratory syncytial virus fusion protein. Three studies (phase Ib/IIa [MK-1654-002], phase IIb/III [CLEVER], and phase III [SMART]) were conducted to evaluate the efficacy, safety, and pharmacokinetics (PK) of clesrovimab in infants. The objectives of this analysis were to develop an infant population PK model for clesrovimab and to evaluate the influence of intrinsic and extrinsic factors on clesrovimab PK in infants. A total of 5850 samples from 2942 participants were included in the population PK analysis. A two-compartment model with first-order absorption and elimination well described clesrovimab PK in infants. The estimated half-life for clesrovimab was 44.0 days. Clearance, absorption rate constant, and central volume of distribution had low inter-individual variability. Body weight was included as a covariate on all clearance and volume parameters, with estimated allometric scaling exponents centered on a body weight of 5 kg. A maturation function further described the change in clearance with increasing infant age. In addition to body weight and maturation function, the final model contained an effect of race on clearance. Although body weight, age, and race were identified as statistically significant covariates, the magnitude of the effect of these covariates on clesrovimab exposures was small (< 30%). The results of the population PK modeling support intramuscular administration of clesrovimab for the prevention of respiratory syncytial virus (RSV) disease in all infants, including healthy infants and infants at increased risk for severe RSV disease.