Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia.
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Savarirayan Ravi, Hoover-Fong Julie, Irving Melita, Arundel Paul, de Bergua Josep Maria, Campeau Philippe M, Candler Toby, Cocanougher Benjamin T, Cormier-Daire Valerie, Edouard Thomas, Fredwall Svein O, Harmatz Paul, Hoernschemeyer Daniel, Irgens Henrik U, Jamuar Saumya, Kannu Peter, Legare Janet M, Leiva-Gea Antonio, McDevitt Helen, Onesimo Roberta, Phillips John, Del Pino Mariana, Robinson Marie-Eve, Rossi Massimiliano, Skae Mars, Ward Leanne M, White Klane K, Schmidt Jane, Lystig Ted, Salvatici Ariana, Bai Yun, Butler Peter W, van Veenhuyzen David, Rogoff Daniela
Аннотация
METHODS: In this phase 3, multicenter, double-blind, placebo-controlled trial, we randomly assigned children with achondroplasia (3 to 17 years of age) in a 2:1 ratio to receive infigratinib (at a dose of 0.25 mg per kilogram of body weight) or placebo once daily for 52 weeks. The primary end point was the change from baseline in the annualized height velocity in the infigratinib group as compared with the placebo group at week 52. Key secondary end points were the change from baseline in the height z score and in the upper-to-lower body segment ratio at week 52. The primary analysis evaluated the treatment effect at week 52 in the full analysis population, with missing data handled with a prespecified imputation approach.
RESULTS: In all, 114 patients underwent randomization: 75 patients to receive infigratinib (with 1 withdrawal before treatment) and 39 patients to receive placebo. The difference between infigratinib and placebo in the least-squares mean change from baseline to week 52 was 1.74 cm per year (95% confidence interval [CI], 1.31 to 2.17; P<0.001) for the annualized height velocity, 0.32 (96% CI, 0.23 to 0.41; P<0.001) for the height z score, and -0.02 (96% CI, -0.06 to 0.01) for the upper-to-lower body segment ratio. Adverse events occurred in 71 of 74 patients (96%) in the infigratinib group and in 37 of 39 patients (95%) in the placebo group; serious adverse events occurred in 4 of 74 patients (5%) and 1 of 39 patients (3%), respectively. No serious adverse events or adverse events leading to treatment discontinuation were considered by the investigator to be related to infigratinib or placebo.
CONCLUSIONS: In children with achondroplasia, treatment with once-daily oral infigratinib for 52 weeks resulted in a significantly greater increase from baseline in the annualized height velocity than placebo. (Funded by BridgeBio Pharma; PROPEL 3 ClinicalTrials.gov number, NCT06164951; EudraCT number, 2023-506130-67.).