There is a clear medical need to find treatment options for childhood ILD. Similarities are found in the pathophysiology of fibrotic lung remodelling in adults and children and the demonstrated benefit of nintedanib in adults with fibrosing ILD1,2. To this end, Dr Robin Deterding (Children’s Hospital Colorado, CO, USA) and colleagues designed the phase 3 InPedILD trial (NCT04093024)3,4.
Patients aged 6-17 with fibrosing ILD (n=39) were randomised 2:1 to nintedanib or placebo in the 24-week, double-blind period. Hereafter, all participants received nintedanib in the open-label phase of the trial. Nintedanib dose was based on weight, ranging from 50 mg, twice daily, for patients between 13.5 and 23 kg, to 150 mg, twice daily, for patients ≥57.5 kg. The co-primary endpoints were area under plasma concentration-time curve at steady state and treatment-emergent adverse events (AEs) after 24 weeks of therapy.
The exposure achieved with weight-based dosing was within the range observed in adults who were treated with nintedanib 150 mg, twice daily. Regarding safety, 84.6% of the patients experienced at least 1 AE, irrespective of treatment arm. As expected by the authors, diarrhoea was the most common AE in the nintedanib arm (38.5%). In the control arm, only 15.4% of the patients experienced diarrhoea. Other frequently reported AEs were vomiting, dental caries, nausea, and abdominal pain, with comparable rates for the 2 study arms.
Although the study was not powered to assess efficacy, the trends favoured the experimental arm: adjusted mean change in FVC % predicted at week 24 was 0.3 for nintedanib versus -0.9 for placebo; adjusted mean change in SpO2 % at rest after 24 weeks of therapy was 0.07 for nintedanib versus -2.25 for placebo.
“These data support a positive benefit-risk assessment for the use of nintedanib in children and adolescents with fibrosing ILD,” concluded Dr Deterding.