A Phase 1b/2a Single Ascending Dose Study of a Half-life Extended RSV Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants

J Infect Dis. 2024 Nov 27:jiae581. doi: 10.1093/infdis/jiae581. Online ahead of print.

Abstract

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 one dose of clesrovimab or placebo. The objectives were to evaluate safety, pharmacokinetics, serum neutralizing antibodies (SNA), and anti-drug antibodies (ADA). The incidence of RSV-associated endpoints [medically-attended lower respiratory tract infection (MALRI), hospitalization, and acute respiratory infection (ARI)] were also evaluated through 150 days postdose.

Results: The most common adverse event (AE) 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 endpoints were lower in infants treated with clesrovimab compared with placebo.

Conclusion: 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: Clinicaltrials.gov, NCT03524118.

Keywords: RSV; clesrovimab; monoclonal antibody.

Plain language summary

Respiratory syncytial virus (RSV) is a major cause of hospitalizations and death among infants. This is the first study of clesrovimab, an anti-RSV antibody, in infants. It was given as a single injection, in four different dose groups and compared to placebo. Clesrovimab was designed to have an extended half-life, meaning it stays in the body for longer than most antibodies. This prolonged presence could potentially provide an extended period of protection against RSV. The side effects reported after a single injection were similar across the placebo and clesrovimab dose groups. The half-life of clesrovimab was approximately 45 days, which is around two times longer than typical antibodies. These findings demonstrate that clesrovimab was generally well tolerated and may have potential as a single-dose preventive measure against RSV in infants. It is currently being studied in late-stage clinical trials.

Associated data

  • ClinicalTrials.gov/NCT03524118