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Published on: January 26, 2019
Clesrovimab in Infants at Increased Risk For Severe Disease During 2 RSV Seasons: A Randomized Clinical Trial
Heather J Zar1, Louis J Bont2,3,4, Paolo Manzoni5,6
1Department of Paediatrics & Child Health and SA-MRC Unit on Child & Adolescent Health, University of Cape Town, Cape Town, South Africa.
Insights
Clesrovimab is safe and well-tolerated for preventing respiratory syncytial virus (RSV) in high-risk infants over two seasons. This supports its use in children continuing to face RSV risk in their second year.
Area of Science:
- Pediatrics
- Immunology
- Infectious Diseases
Background:
- Respiratory syncytial virus (RSV) poses a significant threat to infants, particularly those at high risk for severe lower respiratory tract disease.
- Clesrovimab, a long-acting monoclonal antibody, is approved for first-season RSV prevention, but data for a second season were needed.
Purpose of the Study:
- To evaluate the safety and tolerability of clesrovimab compared to palivizumab in infants during their first RSV season.
- To assess the safety of a higher dose of clesrovimab in the second RSV season for children who remain at risk.
Main Methods:
- A randomized, partially masked, phase 3 clinical trial (SMART study) involving palivizumab-eligible infants.
- Participants received either clesrovimab (105 mg) or palivizumab in season 1, with eligible infants receiving open-label clesrovimab (210 mg) in season 2.
- Primary outcome was the proportion of participants experiencing adverse events in season 1; secondary outcomes included RSV-associated disease incidence.
Main Results:
- Adverse event proportions were comparable between clesrovimab and palivizumab in season 1.
- Clesrovimab (210 mg) was well-tolerated in season 2.
- Incidence of medically attended lower respiratory infection was similar between clesrovimab and palivizumab in season 1 and observed in season 2.
Conclusions:
- Clesrovimab demonstrated good safety and tolerability in high-risk infants through two RSV seasons.
- Findings support the continued use of clesrovimab for children at risk during their second RSV season.
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.
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