Clesrovimab is a monoclonal antibody with anti-RSV activity.
RSV serum neutralizing antibody titer correlates with clesrovimab serum concentration. Following IM administration of clesrovimab in infants, the RSV neutralizing antibody titers in serum were estimated to be approximately 7 times higher than baseline at 4 hours after clesrovimab dosing and maximum titers were reached by day 7, for a typical infant weighing 5 kg.
In the Phase 2b/3 trial evaluating the recommended dose of clesrovimab (a single dose of 105 mg) in healthy preterm and full-term infants (Trial 004), no significant relationship was observed between AUC (from day 1 to day 150) and clinical outcomes (e.g., RSV-associated Medically Attended Lower Respiratory Infection (MALRI)).
Based on clinical trial data, the duration of protection demonstrated by a single dose of clesrovimab extends through 5 months.
The PK of clesrovimab is approximately dose-proportional following a single IM administration of doses ranging from 20 mg to 210 mg in infants. Following IM administration of the 105 mg recommended dose, the geometric mean (% geometric CV) area under the time concentration curve from day 1 to day 150 (AUC0-150) is 6,470 mcg×d/mL (22.6%), peak concentration (Cmax) is 120 mcg/mL (25.4%), and the concentration at day 150 (C150) is 10.3 mcg/mL (36.6%). In the first RSV season, the clesrovimab serum exposures were similar in neonates and infants in Trial 004, in preterm neonates and infants born at less than or equal to 35 weeks GA (including less than 29 weeks GA) in Trial 007, and in neonates and infants with CLD or CHD in Trial 007.
The median time to maximum concentration is 6.5 days (5.9, 7.4 which are the 2.5 and 97.5 percentiles, respectively).
The estimated apparent volume of distribution for clesrovimab is 830 mL, for a typical infant weighing 5 kg.
The clesrovimab terminal half-life is approximately 44.0 days and the estimated apparent clearance is 19.7 mL/day for a typical infant weighing 5 kg.
Clesrovimab is degraded into small peptides by catabolic pathways.
No clinically significant differences in the pharmacokinetics of clesrovimab were observed based on race or vulnerability to severe RSV disease (i.e., CLD, CHD, or GA <29 weeks). An effect of renal or hepatic impairment on clesrovimab pharmacokinetics is not expected.
Since clesrovimab is eliminated by catabolism, no metabolic drug-drug interactions are expected. However, no formal drug interaction studies have been performed with clesrovimab.
Vaccines: In clinical trials, when clesrovimab was given concomitantly with routine childhood vaccines, the safety profile of the co-administered regimen was generally comparable to the safety profile when clesrovimab and childhood vaccines were administered alone.
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