SMART trial supports clesrovimab safety in children at increased RSV risk

Infants at increased risk for severe respiratory syncytial virus (RSV) disease who received clesrovimab had a safety profile comparable to those who received palivizumab during their first RSV season, according to results of the phase 3 SMART trial published in JAMA Pediatrics. The study also found that clesrovimab was generally well tolerated among children who remained at increased risk during a second RSV season.

The findings address a population that includes children with conditions that can leave them at increased risk for severe RSV beyond infancy.

“So let me start with why is this important? You know, it's important because we are talking about a uniquely vulnerable population,” Anushua Sinha, MD, MPH, senior principal scientist at Merck Research Laboratories, told Contemporary Pediatrics. “That's to say, children under two years of age with chronic lung disease, congenital heart disease, or other conditions that put them at increased risk for severe RSV disease when they're entering that second RSV season.”

How did clesrovimab compare with palivizumab in the first RSV season?

SMART was a randomized, partially masked, palivizumab-controlled phase 3 trial conducted at 110 sites in 27 countries and territories. Investigators enrolled infants eligible for palivizumab because of premature birth, chronic lung disease of prematurity, or hemodynamically significant congenital heart disease.

During the first RSV season, 498 infants received a single 105-mg dose of clesrovimab and 499 received monthly palivizumab. The median age was 2.6 months. Adverse events occurred in 75.3% of participants receiving clesrovimab compared with 79.6% receiving palivizumab. Serious adverse events occurred in 24.5% and 27.5%, respectively. No anaphylaxis or hypersensitivity events were reported.

RSV-associated medically attended lower respiratory infection through day 150 occurred at rates of 3.2% with clesrovimab and 3.4% with palivizumab. RSV-associated hospitalization rates were 1.0% and 1.7%, respectively.

What did SMART find during the second RSV season?

A total of 276 children who remained at increased risk received open-label clesrovimab, 210 mg, before their second RSV season. The median age at dosing was 14.4 months.

Among these children, 67.4% experienced at least 1 adverse event and 18.5% experienced a serious adverse event; none of the serious adverse events were considered related to treatment. Injection-site adverse events occurred in 6.5% of children, with injection-site pain the most common. No anaphylaxis or hypersensitivity events were reported.

The second-season findings are particularly relevant because children with chronic lung disease or congenital heart disease can continue to face increased RSV risk during their second year of life.

“We learned that Influencia continues to demonstrate strong clinical data for this population in terms of safety, and that the pharmacokinetics that we observed enable us to bridge, that is to say, extrapolate, to the efficacy that Influencia already demonstrated in the phase two b3 clever study that I mentioned earlier,” Sinha said.

What should pediatricians take from the SMART findings?

The trial was designed primarily to assess safety rather than demonstrate efficacy. Pharmacokinetic findings showed that clesrovimab concentrations during both seasons were similar to concentrations observed among healthy infants in the CLEVER trial, in which efficacy had previously been established.

For pediatricians, Sinha said the findings add to the information available when discussing RSV prevention with families of higher-risk children.

“I would start by saying that immunization decisions should always be guided by rigorous science and comprehensive data, and so I think that the phase 3 smart study results that we're talking about today add to the evidence base that pediatricians have when they're talking to families with young children under 2 years of age who are uniquely vulnerable to RSV because of their underlying health conditions,” Sinha said.

Clesrovimab is currently approved in the United States for prevention of RSV lower respiratory tract disease in neonates and infants born during or entering their first RSV season. The SMART findings provide safety and pharmacokinetic data for children who remain at increased risk during a second season.

“RSV remains a top reason why infants are hospitalized every year, and I'm excited about what the future holds in terms of prevention,” Sinha said. “I hope that pediatricians feel encouraged by the results of the SMART Study and how these data can support their decision-making, their efforts to help reduce the burden of RSV, and how they counsel and work with the families they care for.”

Reference

Zar HJ, Bont LJ, Manzoni P, et al; SMART (MK-1654-007) Study Group. Clesrovimab in infants at increased risk for severe disease during 2 RSV seasons: a randomized clinical trial. JAMA Pediatr. Published online July 20, 2026. doi:10.1001/jamapediatrics.2026.2760.