Design of the PF-ILD trial: a double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease

Abstract

600 patients aged ≥18 years will be randomised in a 1:1 ratio to nintedanib or placebo. Patients with diagnosis of IPF will be excluded. The study population will be enriched with two-thirds having a usual interstitial pneumonia-like pattern on HRCT. The primary endpoint is the annual rate of decline in forced vital capacity over 52 weeks. The main secondary endpoints are the absolute change from baseline in King’s Brief Interstitial Lung Disease Questionnaire total score, time to first acute interstitial lung disease exacerbation or death and time to all-cause mortality over 52 weeks.Ethics and disseminationThe trial is conducted in accordance with the Declaration of Helsinki, the International Conference on Harmonisation Tripartite Guideline for Good Clinical Practice (GCP) and Japanese GCP regulations.Trial registration numberNCT02999178.

Idiopathic and immune‐related pulmonary fibrosis: diagnostic and therapeutic challenges

“…The question remains as to whether we should be characterising disease, and therefore choosing treatment, based on the clinical phenotype or the course of the disease (progressive vs non‐progressive) or the stage of the disease (inflammation in early stage in CTD‐ILD, fibrosis with architectural distortion or honeycombing in the late phases). The question of targeting process or disease pattern instead of specific disease entities is already being challenged and being explored in the progressive disease phenotype studies . With the additional prospect of new drug compounds such as calpain inhibitors or autotaxin inhibitors, an exciting paradigm shift in ILD management is awaited.…”

“…Several studies are underway, where, for example, those with any CTD with a UIP or fibrotic NSIP (‘progressive’) pattern but not OP or cellular NSIP pattern (generally better prognosis without fibrosis) will receive anti‐fibrotic treatment, which so far has only been studied in IPF. The results will potentially significantly change the treatment approach and are keenly awaited …”

“…Such an approach is the focus of a current placebo‐controlled trial entitled Progressive Fibrosing‐ILD (INBUILD study), comparing nintedanib with placebo. This trial excludes patients with IPF but will include patients with UIP‐like pattern (such as in CTD) or non‐UIP pattern (which include NSIP, HP and sarcoid) . In tandem, there is a double‐blind, randomised, placebo‐controlled phase II trial assessing pirfenidone in patients with unclassifiable disease, importantly inclusive of IPAF, and will allow the concomitant use of mycophenolate (NCT03099187).…”

Treating heart failure with preserved ejection fraction: learning from pulmonary fibrosis

“…In the phase III Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis (STEP‐IPF) and INPULSIS trials and the phase II To Improve Pulmonary Fibrosis with BIBF 1120 (TOMORROW) trial, measurements of BNP were longitudinally collected on blood samples. Measurement of BNP is also part of the protocol of two ongoing randomized trials on pulmonary fibrosis, the phase II 1199.36 INSTAGE trial, and the phase III 1199.247 PF‐ILD trial . Data coming from these last two studies, when completed, could be added to the knowledge deriving from the above‐mentioned trials.…”

Prognostic factors and disease behaviour of pathologically proven fibrotic non‐specific interstitial pneumonia

“…In usual interstitial pneumonia (UIP)/IPF, changes in forced vital capacity (FVC) are a reliable, valid and responsive measure of clinical status used as the primary endpoint in pivotal treatment studies . However, the current progressive fibrosing interstitial lung disease (PF‐ILD) study, which is evaluating efficacy and safety of nintedanib in patients with progressive fibrosing interstitial lung disease (ILD) (including f‐NSIP) other than IPF, set annual rate of decline in FVC as the primary endpoint …”