Boehringer Ingelheim Phase III study now enrolling patients with progressive fibrosing lung diseases

For the first time, patients with different fibrosing lung diseases will be included in one single clinical trial assessing the efficacy of nintedanib* as a potential treatment
The PF-ILD clinical trial is the first in the field of fibrosing lung diseases to group patients based on the clinical behaviour of their disease, rather than the diagnosis
In total, 600 patients will be included around the world

Boehringer Ingelheim announced that the first patient has been enrolled in the PF-ILD (progressive fibrosing interstital lung disease) trial. This study investigates the efficacy and safety of nintedanib in a range of progressive fibrosing lung conditions other than idiopathic pulmonary fibrosis (IPF).1

There are over 200 conditions that affect the tissue and space around the air sacs of the lungs (interstitium). These conditions are called interstitial lung diseases or ILDs.2 Based on clinical obervations there are groups of patients with ILD who independent from the classification of the ILD, exhibit a progressive fibrosing behaviour.3-6 The proposed terminology for describing this group of patients is PF-ILD. In these patients the disease appears to follow a course similar to IPF with worsening of respiratory symptoms, lung function, quality of life and ability to perform daily activites, as well as early mortality despite treatment.3-6

“This trial enrolls patients who have lung fibrosis of at least 10% by chest imaging that is getting worse by symptoms, physiology or imaging despite treatment,” said Kevin Flaherty, Coordinating Principal Investigator of the PF-ILD trial. “This trial is an innovative way to study a potential treatment for patients with progressive fibrosing lung diseases and is an important step in exploring the way fibrosis of the lung is treated and whether nintedanib could be an effective therapy.”

Nintedanib, which is marketed as OFEV®, is approved for a rare lung disease called IPF, in which it has been shown to slow disease progression as measured by annual rate of decline in lung function.7-10 Building on the positive real-world clinical experience in IPF, the Phase III trial is now exploring whether nintedanib can effectively target the scarring in the lungs of patients suffering from other progressive fibrosing-ILDs.

“Boehringer Ingelheim is dedicated to advancing the understanding of fibrosing lung diseases where no or limited treatments exist,” said Dr Christopher Corsico, Chief Medical Officer Boehringer Ingelheim. “Our innovative PF-ILD trial is designed to include patients with fibrosing lung diseases who would not otherwise be eligible to participate in a clinical trial. This demonstrates the commitment of Boehringer Ingelheim to transform fibrosing interstitial lung diseases from fatal diseases to chronic, treatable ones.”

About the study11

This double-blind, randomised, placebo-controlled study will evaluate the efficacy and safety of nintedanib 150 mg twice daily over 52 weeks in patients with PF-ILD. The primary endpoint is the annual rate of decline in forced vital capacity (FVC), a measure of disease progression. Other clinical evaluations include the absolute change from baseline in the King’s Brief Interstitial Lung Disease Questionnaire (K-BILD), which measures the health-related quality of life of patients with ILDs to assess the impact of treatment. Other main secondary endpoints include time to first ILD exacerbation and overall survival. The study will include patients with PF-ILD with documented lung scarring on imaging (high-resolution computer tomography, HRCT), and whose lung function and respiratory symptoms or chest imaging have worsened despite treatment.

For more information please visit ClinicalTrials.gov

About PF-ILD

Interstitial lung disease (ILD) encompasses a large group of over 200 lung disorders,2 but there is no widely accepted single classification. Based on clinical observations, there is a group of patients who, independent of their ILD diagnosis, at some point in time develop a progressive phenotpye. Based on their similar disease characteristics, including decline in lung function and early mortality,3-6 it is thought to be appropriate to group these conditions together, regardless of their ILD diagnosis. PF-ILD is the umbrella term for this group of patients.

About OFEV® (nintedanib)

OFEV®(nintedanib, is approved for the treatment of the rare lung disease IPF (idiopathic pulmonary fibrosis).7-10 OFEV® targets growth factor receptors, which have been shown to be involved in the mechanisms by which pulmonary fibrosis occurs. It is believed that nintedanib slows the decline in lung function by blocking the signalling pathways that are involved in fibrotic processes.8,12,13 In animal models, the anti-fibrotic activity of nintedanib was shown to be independent of the cause of the fibrosing lung disease.14

References

1. Clinical trial: Efficacy and Safety of Nintedanib in Patients With Progressive Fibrosing Interstitial Lung Disease. Available at: https://clinicaltrials.gov/ct2/show/NCT02999178 (last accessed 15 March 2017)

2. Valeyre D, et al. Interstitial lung diseases. In: Annesi-Maesano I, Lundbäck B, Viegi G (Eds.), Respiratory Epidemiology 2014; p. 79-87

3. Walsh SL, et al. Connective tissue disease related fibrotic lung disease: high resolution computed tomographic and pulmonary function indices as prognostic determinants. Thorax 2014;69(3):216-22

4. Travis WD, et al. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188(6):733-48

5. Akira M, et al. Long-term follow-up high-resolution CT findings in non-specific interstitial pneumonia. Thorax 2011;66(1):61-5

6. Kim EJ, et al. Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease. Eur Respir J. 2010;35(6):1322-8

7. OFEV® Summary of Product Characteristics. Boehringer Ingelheim International GmbH. January 2017

8. Richeldi L, et al. Design of the INPULSIS® Trials: Two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis. Respir Med. 2014;108:1023-30

9. Richeldi L, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365:1079-1087

10. Richeldi L, et al. Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS® trials. Respir Med. 2016;113:74–79

11. Data on file. Boehringer Ingelheim. PF-ILD Clinical Trial Protocol

12. Hilberg F, et al. BIBF 1120: Triple Angiokinase Inhibitor with Sustained Receptor Blockade and Good Antitumor Efficacy. Cancer Res 2008;68:4774-4782

13. Wollin L, et al. Antifibrotic and Anti-inflammatory Activity of the Tyrosine Kinase Inhibitor Nintedanib in Experimental Models of Lung Fibrosis. J Pharmacol Exp Ther 2014;349:209–220

14. Wollin L, et al. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J 2015;45:1434–144