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DOI: 10.1016/j.jcf.2024.03.012


BACKGROUND: Ivacaftor (IVA) has been shown to be safe and efficacious in children aged ≥4 months with cystic fibrosis (CF) and CFTR gating variants. We evaluated safety, pharmacokinetics (PK), and efficacy of IVA in a small cohort of infants aged 1 toCF.

METHODS: In this phase 3, open-label study, infants 1 toinfants, doses were adjusted at day 15 to better match median adult exposures based on individual PK measurements taken on day 4. Primary endpoints were safety and PK measurements.

RESULTS: Seven infants (residual function CFTR variants [n=5]; minimal function CFTR variants [n=2]) received ≥1 dose of IVA. Six infants had doses adjusted at day 15 and one infant did not require dose adjustment; subsequent PK analyses showed mean trough concentrations for IVA and metabolites were within range of prior clinical experience. Four infants (57.1%) had adverse events (AEs); no serious AEs were noted. One infant discontinued study drug due to a non-serious AE of elevated alanine aminotransferase >8x the upper limit of normal. Mean sweat chloride concentration decreased (-40.3 mmol/L [SD: 29.2]) through week 24. Improvements in biomarkers of pancreatic function and intestinal inflammation, as well as growth parameters, were observed.

CONCLUSIONS: In this small, open-label study, IVA dosing in infants achieved exposures previously shown to be safe and efficacious. Because PK was predictable, a dosing regimen based on age and weight is proposed. IVA was generally safe and well tolerated, and led to improvements in CFTR function, markers of pancreatic function and intestinal inflammation, and growth parameters, supporting use in infants as young as 1 month of age.

Journal Title

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society





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MeSH Keywords

Humans; Cystic Fibrosis; Aminophenols; Quinolones; Infant; Male; Female; Cystic Fibrosis Transmembrane Conductance Regulator; Chloride Channel Agonists; Infant, Newborn; Treatment Outcome


CFTR potentiator; Cystic fibrosis transmembrane conductance regulator; Infants; Ivacaftor; Pharmacokinetics


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