A Phase 1b/2a Single Ascending Dose Study of a Half-life Extended RSV Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants
Shabir A Madhi, Eric A F Simões, Armando Acevedo, Jose M Novoa Pizarro, Julie S Shepard, Radha A Railkar, Xin Cao, Brian M Maas, Xiaowei Zang, Andrea Krick, Brad Roadcap, Kalpit A Vora, Antonios O Aliprantis, Andrew W Lee, Anushua SinhaAbstract
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