Nintedanib in patients with chronic fibrosing Interstitial lung diseases with progressive phenotype: the INBUILD trial*

Introduction: Nintedanib is an approved treatment for idiopathic pulmonary fibrosis (IPF). Pre-clinical data suggest that nintedanib inhibits processes fundamental to progression of lung fibrosis irrespective of the aetiology.

Aim: The INBUILD trial was designed to investigate the efficacy and safety of nintedanib in patients with various non-IPF chronic fibrosing ILDs with progressive phenotype.

Methods: Eligible patients had diffuse fibrosing lung disease of > 10% extent on HRCT, FVC ≥ 45% predicted, DL_CO ≥ 30-<80% predicted, and met ≥ 1 of 4 criteria for ILD progression ([Table 1]) in the 24 months before screening, despite treatment of ILDs in clinical practice. Patients with IPF were excluded. Subjects were randomised to receive nintedanib 150 mg bid or placebo. The primary endpoint is the annual rate of decline in FVC (mL/yr) assessed over 52 weeks. There will be two co-primary analysis populations: all subjects and subjects with a UIP-like fibrotic pattern only on HRCT.

Table 1 Baseline characteristics of patients in the INBUILD trial (n = 663).

Data are mean ± standard deviation or n (%) of randomised patients treated with ≥ 1 dose of trial drug. * Categories shown are those provided as options on the case report form. ** As reported by the investigator on case report form: ≥ 1 category could be ticked. *** Meeting criteria A, B and C; A and C; or B and C as follows: (A) Definite honeycomb lung destruction with basal and peripheral predominance. (B) Presence of reticular abnormality and traction bronchiectasis consistent with fibrosis with basal and peripheral predominance. (C) Atypical features are absent, specifically nodules and consolidation: ground glass opacity, if present, is less extensive than reticular opacity pattern. It was planned to randomise ≥ 400 patients with UIP-like fibrotic pattern only on HRCT and ~ 200 patients with other fibrotic patterns on HRCT.
Male	356 (53.7)
Age, years	65.8 ± 9.8
BMI, kg/m²	28.3 ± 5.3
Race
White	487 (73.5)
Asian	163 (24.6)
Other/missing	13 (2.0)
Tobacco use
Never	329 (49.6)
Former	321 (48.4)
Current	13 (2.0)
Time since ILD diagnosis, years, median (25th percentile, 75th percentile)	2.5 (1.2, 5.0)
ILD diagnosis*
Hypersensitivity pneumonitis	172 (25.9)
Idiopathic NSIP	125 (18.9)
Unclassifiable IIP	115 (17.3)
Rheumatoid arthritis-associated ILD	88 (13.3)
Exposure-related ILD	39 (5.9)
Systemic sclerosis-associated ILD	39 (5.9)
Mixed connective tissue disease ILD	20 (3.0)
Sarcoidosis	12 (1.8)
Other fibrosing ILDs	53 (8.0)
Criteria for ILD progression in 24 months before screening**
Relative decline in FVC ≥ 10% predicted	337 (50.8)
Relative decline in FVC ≥ 5 – < 10% predicted and increased extent of fibrotic changes on imaging	194 (29.3)
Relative decline in FVC ≥ 5 – < 10% predicted and worsened respiratory symptoms	97 (14.6)
Worsened respiratory symptoms and increased extent of fibrotic changes on imaging	241 (36.3)
Missing	2 (0.3)
FVC, mL	2327 ± 737
FVC, % predicted	69.0 ± 15.7
< 80% predicted	498 (75.1)
≥ 80% predicted	161 (24.3)
Missing	4 (0.6)
DLCO, % predicted	47.6 ± 32.2
K-BILD total score	51.2 ± 10.1
UIP-like fibrotic pattern only on HRCT***	411 (62.0)

Results: 663 patients were randomised and treated ([Table 1]). Mean (± SD) age was 65.8 ± 9.8 years, FVC was 69.0 ± 15.7% predicted, DLco was 47.6 ± 32.2% predicted.

Conclusions: The INBUILD trial will provide insights into the natural history and role of nintedanib in treating patients with various progressive fibrosing ILDs. Results will be presented at the congress.

* presented at ERS 2019; ^‡ presenting on behalf of the authors