Ped endo journal scan

Objective: The study was aimed at determining whether oral infigratinib, a fibroblast growth factor receptor 1 through 3 selective tyrosine kinase inhibitor, is superior to placebo in improving annualized height velocity (AHV) in children with achondroplasia. Study Methodology and Results:In this phase 3, double-blinded, randomized, placebocontrolled trial conducted at 27 sites across 10 countries, children aged 3-17 years with genetically proven achondroplasia and remaining growth potential (baseline AHV >1.5 cm/year, Tanner stage ≤4, and skeletal age ≤13 years in girls and ≤15 years in boys) were randomized in a 2:1 ratio to receive either daily oral infigratinib (0.25 mg/kg/day) or oral placebo.The primary endpoint was the between-group difference in the change from baseline in AHV at week 52.Key secondary endpoints included the between-group difference in the change from baseline to week 52 in height Z-score and upper-to-lower body segment ratio (US: LS).Between November 2023 and December 2024, a total of 114 children underwent randomization, 75 to the infigratinib arm and 39 to the placebo arm.The mean ± standard deviation age at enrolment was 7.9 ± 2.7 years; 58% of patients were males; and 83% were prepubertal.The baseline characteristics were similar between the two groups.At week 52, the least-squares mean change from baseline in AHV was 1.58 cm/year (95% confidence interval [CI]: 1.21-1.94cm/year) in the infigratinib group and -0.16 cm/year (95% CI: -0.61-0.28cm/year) in the placebo group; the between-group difference was 1.74 cm/year (95% CI: 1.31-2.71cm/year; p < 0.001).Subgroup analysis revealed that the efficacy of infigratinib did not vary by age, sex, pubertal status, baseline height Z-score, and baseline AHV.Among key secondary endpoints, the difference between infigratinib and placebo in the least-squares mean change from baseline to week 52 in the achondroplasia-specific height Z-score was 0.23 (95% CI: 0.23-0.41)and that in the US: LS was -0.02 (95% CI: -0.06-0.01).One or more adverse events (AEs) were reported in 96% of patients in the infigratinib arm and 95% in the placebo arm, with 8% and 15%, respectively, attributed to the trial intervention.Serious AEs occurred in 5% and 3% of patients, respectively; none were considered by the investigator to be related to infigratinib or placebo therapy.Mean serum phosphate levels remained consistent and comparable across the two groups throughout the entire duration of the study.No rapid advancement of skeletal age was observed.