TABLE 2.

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; D_LCO: diffusing capacity of the lung for carbon monoxide; FHP: fibrotic hypersensitivity pneumonitis; ER: emergency room; F_IO2: inspiratory oxygen fraction; HRCT: high-resolution computed tomography; HP: hypersensitivity pneumonitis.