Oral Infigratinib in Pediatric Achondroplasia: Phase 3 Trial

Key Takeaways

• A greater week-52 change from baseline in annualized height velocity was observed with infigratinib than with placebo.
• Change in height z score also favored infigratinib, while change in upper-to-lower body segment ratio showed a small between-group difference.
• Adverse events were common in both groups, and serious adverse events were uncommon.

In a phase 3 trial, children with achondroplasia receiving once-daily oral infigratinib had a week-52 least-squares mean change from baseline in annualized height velocity that exceeded placebo by 1.74 cm per year. The 95% confidence interval was 1.31 to 2.17, and the between-group comparison met a P value threshold of less than 0.001.

The phase 3 trial used a multicenter, double-blind, placebo-controlled design in children with achondroplasia who were 3 to 17 years of age. Participants were randomly assigned in a 2:1 ratio to oral infigratinib 0.25 mg per kilogram once daily or placebo for 52 weeks. Among 114 randomized patients, 75 were assigned to infigratinib and 39 to placebo, with one withdrawal before treatment in the infigratinib group. The primary endpoint was change from baseline in annualized height velocity at week 52, and key secondary endpoints were change in height z score and upper-to-lower body segment ratio.

At week 52, the least-squares mean difference in change from baseline for height z score was 0.32, with a 96% confidence interval of 0.23 to 0.41 and P<0.001. The corresponding least-squares mean difference in change from baseline for upper-to-lower body segment ratio was -0.02, with a 96% confidence interval of -0.06 to 0.01. Height z score favored infigratinib, while the body proportion measure showed a small between-group separation.

Adverse events occurred in 71 of 74 patients, or 96%, in the infigratinib group and in 37 of 39 patients, or 95%, in the placebo group. Serious adverse events occurred in 4 of 74 patients, or 5%, and 1 of 39 patients, or 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.