Clesrovimab through a second RSV season

Design

phase 3, randomised, partially masked, palivizumab-controlled trial at 110 sites in 27 countries

Population

997 palivizumab-eligible infants with prematurity, chronic lung disease of prematurity or significant congenital heart disease, median age 2.6 months

Primary outcome

proportion of participants experiencing adverse events after clesrovimab or palivizumab in season 1

Effect

adverse events comparable between groups; RSV-associated medically attended lower respiratory infection 3.2% (95% CI 1.8 to 5.2) vs 3.4% (2.0 to 5.6) through day 150

SMART randomised 997 palivizumab-eligible infants - prematurity, chronic lung disease of prematurity, or haemodynamically significant congenital heart disease - to a single 105 mg dose of clesrovimab or five monthly doses of palivizumab, across 110 sites in 27 countries. Those still at risk received open-label clesrovimab 210 mg before their second season.

Adverse event rates were comparable between the two in season 1, and the 210 mg second-season dose was well tolerated in the 276 children who received it. RSV-associated medically attended lower respiratory infection through day 150 was 3.2% with clesrovimab and 3.4% with palivizumab; through day 180 after the second-season dose it was 7.3%.

The practical difference is one injection instead of five. For a family bringing a preterm infant back monthly through an RSV season, that is the whole of the burden of prophylaxis, and adherence to five doses is imperfect everywhere. Note what this trial was and was not designed to do: the primary outcome was safety, and the disease incidence figures are descriptive comparisons rather than a powered efficacy test. It does not establish that clesrovimab prevents as much RSV disease as palivizumab; it establishes that it is tolerated and that the observed rates were similar.

• Identify children who will still be at increased risk entering a second RSV season - chronic lung disease and significant congenital heart disease, mainly
• A single dose replaces five, so count adherence as part of the comparison rather than only efficacy
• The efficacy comparison here is descriptive; do not present it to parents as proven equivalence
• Cost and availability, not evidence, will decide this in most Indian units

The statistics, in plain English

The primary endpoint was the proportion with adverse events, so this is a safety trial with efficacy described alongside. The incidence figures carry wide intervals - 1.8% to 5.2% for clesrovimab, 2.0% to 5.6% for palivizumab - which overlap almost entirely and would be compatible with a meaningful difference in either direction. That is the expected consequence of counting a few dozen events. The second-season figure of 7.3% has no comparator at all, because that phase was open-label and single-arm; it describes what happened, not what was prevented. Partial masking, rather than full blinding, was necessary because the two regimens differ in number of injections.

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