JAMA pediatrics
September 1, 2026 · via Europe PMC
Clesrovimab in Infants at Increased Risk For Severe Disease During 2 RSV Seasons: A Randomized Clinical Trial.
Zar HJ, Bont LJ, Manzoni P, +21 more, SMART (MK-1654-007) study group.
AI summary — for doctors, generated from the abstract only
Clesrovimab was as well tolerated as palivizumab in high-risk infants in their first RSV season and well tolerated at a higher dose in the second season.
What was studied
The SMART phase 3, randomised, partially masked trial at 110 sites in 27 countries in 997 palivizumab-eligible infants (prematurity, chronic lung disease or significant CHD) receiving clesrovimab 105 mg or monthly palivizumab, with open-label clesrovimab 210 mg in season 2 (n=276).
Key findings
- Adverse event proportions comparable between groups in season 1
- RSV MALRI through day 150: 3.2% clesrovimab vs 3.4% palivizumab
- Season 2 clesrovimab 210 mg well tolerated; RSV MALRI 7.3% through day 180
Clinical relevance
This supports clesrovimab as a single-dose option for high-risk infants and for those remaining at risk in their second season.
Who should care
Limitations
Primary endpoint was safety, not efficacy; season 2 was open-label without a comparator.
A single dose of clesrovimab appears a safe alternative to monthly palivizumab for high-risk infants.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Importance
Clesrovimab is a long-acting monoclonal antibody approved for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants who are born during or entering their first RSV season; data concerning clesrovimab from a second RSV season among children who remain at risk for severe disease are needed.
Objective
To evaluate the safety and tolerability of clesrovimab (105 mg) vs palivizumab in RSV season 1 in infants at increased risk for severe RSV disease. Key secondary objectives include describing the safety of 210 mg of clesrovimab in RSV season 2 in children who remain at increased risk for severe RSV disease, clesrovimab pharmacokinetics, and the incidence of RSV-associated disease.
Design, setting, and participants
SMART (MK-1654-007) was a randomized, partially masked, palivizumab-controlled, phase 3 clinical trial, conducted at 110 sites in 27 countries and territories between November 30, 2021, and November 20, 2025. The population constituted palivizumab-eligible infants, including those with prematurity, chronic lung disease of prematurity, or hemodynamically significant congenital heart disease.
Interventions
Participants, randomized 1:1 and stratified by region and condition, received clesrovimab (105 mg) on day 1 followed by placebo on day 28 or monthly palivizumab (15 mg/kg) up to 5 doses (1 dose per month). Eligible infants received open-label clesrovimab (210 mg) before their second RSV season.
Main outcomes and measures
The primary outcome was the observed proportions of participants experiencing adverse events (AEs) after clesrovimab or palivizumab in season 1.
Results
Overall, 997 infants (500 [50.2%] male; median age, 2.6 [range, 0.0-12.0] months) received clesrovimab, 105 mg (n = 498) or palivizumab (n = 499) in season 1; 276 received clesrovimab, 210 mg open-label in season 2. In season 1, the proportions of participants experiencing AEs were comparable between treatment groups. In season 2, clesrovimab, 210 mg was well tolerated. Incidence rates of RSV-associated medically attended lower respiratory infection (MALRI) were comparable between clesrovimab and palivizumab (3.2% [95% CI, 1.8%-5.2%] and 3.4% [95% CI, 2.0%-5.6%], respectively) through day 150 in season 1; total RSV-associated MALRI incidence through day 180 after a 210-mg dose in season 2 was 7.3% (95% CI, 4.4%-11.4%).
Conclusions and relevance
In this randomized clinical trial, clesrovimab was well tolerated in infants at increased risk for severe RSV disease through 2 RSV seasons. These findings support the use of clesrovimab in children who remain at risk for severe RSV disease in their second RSV season.
Trial registration
ClinicalTrials.gov Identifier: NCT04938830.
DOI
10.1001/jamapediatrics.2026.2760
PMID
42475081
PMCID
PMC13386298
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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