Results of a global phase III clinical trial of nintedanib in the treatment of progressive fibrotic interstitial lung disease in children and adolescents were announced

In September, Boehringer Ingelheim announced positive results from a global Phase III clinical trial of Nintedanib™ for the treatment of children and adolescents aged 6-17 years with progressive fibrotic interstitial lung disease, reaching the primary composite endpoint
.

"Based on the mechanism of action of nintedanib, data from preclinical studies, and clinical benefits in adult patients, there are compelling reasons to explore its role in children with interstitial lung disease," said
Professor Robin Deterding, MD, director of the Institute of Respiratory Diseases at Children's Hospital Colorado.
"This trial supports nintedanib as a potentially safe and acceptable treatment for
progressive fibrotic interstitial lung disease in children and adolescents.
There are currently no approved evidence-based treatments
for this group.
”

Interstitial lung disease in children (chILD) encompasses more than 200 rare diseases that cause symptoms including cough, dyspnea, and shortness of breath [^4],[5].

Its exact incidence is unknown, but its reported incidence ranges from 1.
5 to 3.
8 cases per million population, which can be considered extremely rare ^[4].

The incidence of pulmonary fibrosis is even lower in patients with chILD, the global prevalence is not known, and there have not been any international multicenter studies prior to InPedILD ^[4].

chILD is associated with significant mortality and morbidity ^[6].

When the condition worsens, many pediatric patients need oxygen to maintain daily life and require lung transplants [^{5], [6].}

There are no established diagnostic criteria, and management guidelines are rare [4],^[7],[8].

Current standards of care involve out-of-label treatments, including steroids and immunosuppressants
.
These agents have adverse effects and evidence is limited ^[4].

InPedILD™, a double-blind, randomized, placebo-controlled global phase III trial, is the first placebo-controlled global study of interstitial lung disease in children to evaluate the dose-exposure and safety
of nintedanib in children and adolescents aged 6 to 17 years with progressive fibrotic interstitial lung disease.
Patients were randomized 2:1 to receive either nintedanib (n=26) or placebo (n=13) for 24 weeks, followed by open-label nintedanib treatment
.
The primary composite endpoint was the area under the plasma concentration-time curve (AUC) at steady-state at weeks 2 and 26 and the proportion of patients experiencing adverse events during the
24-week treatment period.

The results showed that the AUC of nintedanib was 175μg*h/L (85.
1) in patients aged 6~11 years and 160μg*h/L (82.
7) in patients aged 12~17 years, indicating that the exposure of nintedanib weight-based dosing regimen in children and adolescents was comparable
to that of adults.
The safety profile is similar to previous adult studies and is acceptable for children and adolescents
.
The trial results were published in the European Journal of Respiration (ERJ) and presented
at the Congress of the European Respiratory Society (ERS) in Barcelona, Spain.

Dr Susanne Stowasser, Deputy Director of the Department of Pulmonology at Boehringer Ingelheim, said: "Although interstitial lung disease in children is very rare, the impact of the disease on children, adolescents and their loved ones can be devastating
.
The findings from InPedILD help address the urgent need
for targeted therapies in these children and adolescents with ILD.
These data will also further support Boehringer Ingelheim's ongoing commitment to addressing unmet clinical needs and driving research for patients with pulmonary fibrosis of all ages
.
" ”

References:

       [1] Flaherty KR, Wells AU, Cottin V, et al.
Nintedanib in progressive fibrosing interstitial lung diseases.
N Engl J Med.
2019; 381(18):1718-1727.
doi: 10.
1056/NEJMoa1908681.

       [2] European Commission decision, July 13, 2020.
data on file.

       [3] U.
S.
Food and Drug Administration news release.
FDA Approves First Treatment for Group of Progressive Interstitial Lung Diseases.
Available at Last accessed August 2020.

       [4] Deterding R.
et al.
Study design of a randomised, placebo controlled

trial of nintedanib in children and adolescents with fibrosing interstitial lung disease.
ERJ Open Res.
2021 Jun 21; 7(2):00805-2020

[5] Deterding R.
et al.
Approaching Clinical Trials in Childhood Interstitial Lung Disease and Pediatric Pulmonary Fibrosis.
Am J Respir Crit Care Med.
2019 Nov 15; 200(10):1219-1227.

       [6] Cunningham S.
et al.
Childrens interstitial and diffuse lung disease.
Lancet Child Adolesc Health.
2019; 10.
1016/S2352-4642(19)30117-8.

[7] Kurland et al.
An official American Thoracic Society clinical practice guideline.
Am J Respir Crit Care Med.
2013 Aug 1; 188(3):376-94.

[8] Bush et al.
European protocols for the diagnosis and initial treatment of interstitial lung disease in children.
Thorax.
2015 Nov; 70(11):1078-84

About ILD

Interstitial lung disease (ILD) is a general term
for a large group of heterogeneous diseases with common features in clinical (oxygenation disorders), imaging (signs of diffuse lesions), pathology (inflammation and fibrosis), and different etiology.
ILD is known to include more than 200 diseases, and has been regarded as a difficult condition
in the respiratory field because of its broad and complex etiological spectrum and difficulty in diagnosis and treatment 。 Because some ILD lesions invade the lung interstitium, they can also involve the alveoli, pulmonary capillary endothelial cells and bronchioles, etc.
, and there are lung parenchymal changes such as alveolitis, protein exudation in the alveolar cavity, etc.
, which are manifested as alveo-interstitial diseases on chest imaging, so ILD is also called diffuse parenehymal lung disease (DPLD); Also known as diffuse lung disease (DLD).

About InPedILD™

This double-blind, randomized, placebo-controlled, multicenter international phase III clinical trial [NCT04093024] enrolled patients
in approximately 43 research centers in 21 countries.
The study, conducted in children and adolescents (6 to 17 years of age) with clinically significant progressive fibrotic ILD, will evaluate the dose-exposure and safety of nintedanib that is taken orally for 24 weeks in addition to usual care, followed by continued nintedanib open therapy
.