End-points
| Primary end-point |
| Mean change from baseline to week 52 in FVC % predicted |
| Secondary end-points |
| Progression-free survival defined as the time from study treatment randomisation to the first occurrence of any of the following events: Relative decline from baseline of ≥10% in FVC and/or DLCO Acute exacerbation of FHP defined as acute respiratory declined leading to hospitalisation or ER or urgent care evaluation; evidence of all of the following criteria within a 4-week period in the outpatient setting: |
| • Increase from baseline FIO2 ≥1 L oxygen |
| • Clinically significant worsening of dyspnoea and/or cough |
| • New, superimposed ground-glass opacities or consolidation or new alveolar opacities on chest radiography or CT |
| • Primary: if all other causes excluded (e.g. acute gastro-oesophageal aspiration, pneumothorax, infection, left heart failure, pulmonary embolism, or identifiable cause of acute lung injury) |
| A decrease from baseline of at least 50 m in 6-min walk distance |
| Change in background therapy (need for a new course of p.o. or i.v. steroids or for the patient receiving maintenance prednisone, as a need to increase the dose by 10 mg or more; and/or addition of cyclophosphamide, azathioprine, mycophenolate mofetil or mycophenolic acid) |
| Death |
| Slope of FVC over 52-week treatment period |
| Mean change in DLCO % predicted at week 52 |
| Proportion of patients with all-cause mortality |
| Proportion of patients with all-cause hospitalisation |
| Proportion of patients with hospitalisation for respiratory cause |
| Proportion of patients with respiratory exacerbations requiring hospitalisations |
| Proportion of patients with evidence of progression of fibrosis on visual comparison of baseline and week 52 HRCT scans |
| Exploratory end-points |
| Mean change from baseline in health-related quality of life, measured by St. George's Respiratory Questionnaire (3 domain scores and total score), at Week 52 |
| Mean change from baseline in health-related quality of life, measured by A Tool to Assess Quality of Life Questionnaire at Week 52 |
| Mean change from Baseline to Week 52 in dyspnoea as measured by the University of California at San Diego Shortness-of-Breath Questionnaire score |
| Proportion of patients with evidence of progression, stability or improvement in fibrosis on texture-based quantitative analysis of CT |
| Candidate biomarker expression in the peripheral blood of patients with HP over the 52-week study follow-up period |
| Safety end-points |
| Proportion of patients with treatment-emergent adverse events |
| Proportion of patients with treatment-emergent serious adverse events |
| Proportion of patients with treatment-emergent adverse drug reaction |
| Proportion of patients with treatment-emergent serious drug reaction |
| Proportion of patients with adverse events leading to early discontinuation of study treatment |
| Proportion of patients with treatment-emergent deaths |
| Proportion of patients with treatment-emergent changes in clinical laboratory findings and ECGs |
FVC: forced vital capacity; DLCO: diffusing capacity of the lung for carbon monoxide; FHP: fibrotic hypersensitivity pneumonitis; ER: emergency room; FIO2: inspiratory oxygen fraction; HRCT: high-resolution computed tomography; HP: hypersensitivity pneumonitis.