Randomised controlled trials evaluating antifibrotic treatments in patients with interstitial lung disease (ILD)

Study identifier [ref.]Study/phasePatients nDuration of studyKey primary outcomesKey secondary outcomes
NCT02597933 [90, 91]Phase III SENSCIS (Safety and Efficacy of 150 mg nintedanib twice daily in Systemic SClerosIS) study in patients with SSc-ILD58052 weeksAnnual rate of decline in FVCChange in the mRSS; change in SGRQ score; change in FVC % pred and DLCO % pred; change in digital ulcer burden
NCT02999178 [1, 92]Phase III (INBUILD) efficacy and safety of 150 mg nintedanib twice daily in patients with PF-ILD66352 weeksAnnual rate of decline in FVCChange in K-BILD score; time to first exacerbation; overall survival
NCT03283007 [93]Phase III trial (INFINITYx-BOS) investigating the efficacy of 150 mg nintedanib twice daily in lung transplant patients with grade 1–2 BOSNot yet recruiting6 monthsEfficacy in the reduction of the rate of decline of FEV1Efficacy on exercise tolerance; QoL; FEV1 decrease; progression of BOS; change in oxygen saturation; tolerance in lung transplant recipients; explanatory parameters of fibrotic pathways
EudraCT 2014–000861-32 DRKS00009822 [94]#Phase II (RELIEF) efficacy and safety of 2403 mg oral pirfenidone daily as add-on to existing treatment for progressive, non-IPF lung fibrosis (CTD-ILD; fNSIP; cHP; ALF)37448 weeksAbsolute change in FVC % predTime to disease worsening; changes in DLCO, 6MWT distance QoL scores (SGRQ and EQ-5D); safety and tolerability
NCT02808871 [45]Phase II study of pirfenidone three times daily (2403 mg) as add-on to existing treatment in patients with RA-ILDEstimated 270 (still recruiting)52 weeksComposite end-point: PFS (≥10% decline in FVC or death)Relative decline in DLCO (≥15%); FVC % pred (≥10%); incidence of acute exacerbations, dyspnoea scores; SGRQ scores; safety and tolerability
NCT02958917 [95]Phase II study of efficacy and safety of 2403 mg pirfenidone daily in patients with fHPEstimated 40 (still recruiting)52 weeksMean change in FVC % predPFS; ≥5% mean change in FVC % pred; acute exacerbations; decrease in 6MWT distance
NCT02496182 [96]Phase II/III study of pirfenidone 1800 mg or 1200 mg daily as add-on to existing treatment in patients with cHPEstimated 60 (recruiting status unknown)52 weeksFVC at week 26 and week 52Inflammation and fibrosis grade on HRCT using Kazerooni scale; 6MWT distance
NCT03099187 [97]Phase II multicentre, international, double-blind, two-arm, randomised, placebo-controlled study of 2403 mg pirfenidone daily in patients with unclassifiable PF-ILD. Some patients may continue with MMF25024 weeksRate of decline in FVC (mL)Change in FVC % pred; change in DLCO % pred; change in 6 MWT distance; patient reported outcomes (including SGRQ); safety and tolerability
NCT02821689 [98]Phase 4 study of 1800 mg pirfenidone daily as add-on to existing treatment in progressive ILD associated with CADMEstimated 57 (recruiting status unknown)52 weeksOSChanges in HCRT features; pulmonary function
NCT02262299 [99]Phase II/III European trial of 2403 mg pirfenidone daily in patients with BOS, a European multicentre study (EPOS)Estimated 80 (still recruiting)26 weeksChange in FEV1Change in FVC; change in DLCO % pred; change in 6MWT distance; change in BOS grade; hospitalisation, survival and re-transplantation rates
NCT03385668 [7]Phase II trial (PIRFENIVAS) of 2403 mg pirfenidone daily in patients with pulmonary fibrosis with MPO antibodies or with anti-MPO associated vasculitisEstimated 15 (still recruiting)52 weeksAbsolute change in FVC% predTreatment emergent AEs; SAEs; cause of death; vital signs; change in absolute FVC % pred; relative change in FVC % pred or a decline of FVC <10%; 6MWT distance; percentage change in DLCO; PFS; dyspnoea; change in chest CT scan abnormalities; QoL
NCT03260556 [22]Phase IV trial (PirFS) of 2403 mg pirfenidone daily in patients with advanced fibrotic sarcoidosisEstimated 60 (still recruiting)2 yearsTime until clinical worseningChange in FVC; change in composite physiologic index
NCT03221257 [100]Phase II trial (SLSIII) of 2403 mg pirfenidone plus 3000 mg MMF daily in 2-week intervals15018 monthsPercent change in FVC % predChange in DLCO % pred; change in mRSS; change in transitional dyspnoea index; change in health assessment questionnaire modified for scleroderma (SHAQ), SGRQ; change in chest CT scan abnormalities

SSc-ILD: systemic sclerosis-associated ILD; FVC: forced vital capacity; mRSS: modified Rodnan skin score; SGRQ: St George's Respiratory Questionnaire; DLCO: diffusing capacity of the lung for carbon monoxide; PF-ILD: progressive-fibrosing ILD; K-BILD: King's Brief Interstitial Lung Disease questionnaire; BOS: bronchiolitis obliterans; FEV1: forced expiratory volume in 1 s; QoL: quality of life; IPF: idiopathic pulmonary fibrosis; CTD-ILD: connective tissue disease associated-ILD; fNSIP: fibrotic nonspecific interstitial pneumonia; cHP: chronic hypersensitivity pneumonitis; ALF: asbestos-related lung fibrosis; EQ-5D: EuroQol 5-level questionnaire; RA-ILD: rheumatoid arthritis-associated ILD; PFS: progression-free survival; fHP: fibrotic hypersensitivity pneumonitis; 6MWT: 6-min walk test; HRCT: high-resolution computed tomography; MMF: mycophenolate mofetil; CADM: clinically amyopathic dermatomyositis; AE: adverse event; MPO: myeloperoxidase; SAE: serious adverse event; CT: computed tomography. #: prematurely ended. Reproduced and modified from [87] with permission.