Clesrovimab for Prevention of RSV Disease in Healthy Infants
One 105-mg dose of clesrovimab significantly reduced RSV medically attended lower respiratory infection and hospitalization over 5 months in healthy infants.Multicenter double-blind randomized placebo-controlled trial; Level 1b (2011 OCEBM).
Background
Respiratory syncytial virus (RSV) causes major infant morbidity. Clesrovimab is a long-acting monoclonal antibody targeting RSV F protein site IV; its efficacy and safety in healthy infants were unknown.
Patients
Healthy preterm and full-term infants <1 year entering their first RSV season across 22 countries; 3614 injected (clesrovimab 2412; placebo 1202). Median age 3.1 months; 79.9% <6 months; 82.5% ≥35 weeks. Palivizumab-eligible infants were excluded.
Intervention
Single intramuscular clesrovimab 105 mg.
Control
Matching placebo.
Outcome
Primary: RSV-associated medically attended lower respiratory infection (≥1 indicator) through day 150. Key secondary: RSV-associated hospitalization through day 150.
Follow up period
Efficacy to days 150 and 180; safety ≥240 days; season 2 surveillance days 365–515.
Results
| Outcome | Timeframe | Clesrovimab (n/N, %) | Placebo (n/N, %) | Efficacy % (95% CI) | NNT |
|---|---|---|---|---|---|
| Primary: RSV medically attended LRI (≥1 indicator) | 150 days | 60/2398 (2.6) | 74/1201 (6.5) | 60.4 (44.1–71.9) | 26 |
| Secondary: RSV-associated hospitalization | 150 days | 9/2398 (0.4) | 28/1201 (2.4) | 84.2 (66.6–92.6) | 50 |
| Post hoc: RSV medically attended LRI (≥2 indicators) | 150 days | 10/2398 (0.4) | 41/1201 (3.5) | 88.0 (76.1–94.0) | 33 |
| Tertiary: Hospitalization for LRI (any cause) | 150 days | 5/2398 (0.2) | 27/1201 (2.3) | 90.9 (76.2–96.5) | 48 |
Limitations
- Primary endpoint definition differs from other trials; post hoc analyses.
- Subgroup estimates imprecise (few events).
- High-risk (palivizumab-eligible) infants excluded.
- Follow-up focused on first season; long-term impact of antidrug antibodies unclear.
- Manufacturer-funded trial.
Funding
Industry-funded (Merck Sharp & Dohme); potential sponsor bias.
Citation
Zar HJ, Simões EAF, Madhi SA, et al. Clesrovimab for Prevention of RSV Disease in Healthy Infants. N Engl J Med. 2025;393:1292-1303. DOI: 10.1056/NEJMoa2502984.