Childhood interstitial lung disease comprises a spectrum of rare ILDs affecting infants, children and adolescents. Nintedanib is a licensed treatment for pulmonary fibrosis in adults. The primary objectives of the InPedILD trial were to determine the dose-exposure and safety of nintedanib in children and adolescents with fibrosing ILD. Patients aged 6-17 years with fibrosing ILD on HRCT and clinically significant disease were randomised 2:1 to receive nintedanib or placebo for 24 weeks then open-label nintedanib. Dosing was based on weight-dependent allometric scaling. Co-primary endpoints were the area under the plasma concentration-time curve at steady state (AUC(τ,ss)) at weeks 2 and 26 and the proportion of patients with treatment-emergent adverse events at week 24. Twenty-six patients received nintedanib and 13 placebo. The geometric mean (gCV%) AUC(τ,ss) for nintedanib was 175 µg×h·L(-1) (85.1) in patients aged 6-11 years and 160 µg×h·L(-1) (82.7) in patients aged 12-17 years. In the double-blind period, adverse events were reported in 84.6% of patients in each treatment group. Two patients discontinued nintedanib due to adverse events. Diarrhoea was reported in 38.5% and 15.4% of the nintedanib and placebo groups, respectively. Adjusted mean (se) changes in FVC % predicted at week 24 were 0.3 (1.3) in the nintedanib group and -0.9 (1.8) in the placebo group. In conclusion, in children and adolescents with fibrosing ILD, a weight-based dosing regimen resulted in exposure to nintedanib similar to adults and an acceptable safety profile. These data provide a scientific basis for the use of nintedanib in this patient population.
- Deterding, R.
- Young, L. R.
- DeBoer, E. M.
- Warburton, D.
- Cunningham, S.
- Schwerk, N.
- Flaherty, K. R.
- Brown, K. K.
- Dumistracel, M.
- Erhardt, E.
- Bertulis, J.
- Gahlemann, M.
- Stowasser, S.
- Griese, M.