Objectives and end-points of the ATLAS study
| Objectives | End-points | |
| Primary | To assess the effect of dupilumab on preventing or slowing the rate of LFD at year 1 in the FeNO population compared to placebo | Rate of change from week 8 to year 1 in the post-BD FEV1 (post-BD FEV1 slope) in the FeNO population |
| Key secondary | To assess the effect of dupilumab on slowing the rate of LFD at year 1 in the total population compared with placebo | Rate of change from week 8 to year 1 in post-BD FEV1 (post-BD FEV1 slope) in the total population |
| To assess the effect of dupilumab on slowing the rate of LFD at year 2 in the FeNO population compared with placebo | Rate of change from week 8 to year 2 in post-BD FEV1 (post-BD FEV1 slope) in the FeNO population | |
| Other secondary | Effect of dupilumab in improving lung function parameters, exacerbations, asthma control and biomarker levels at year 1 and year 2 compared with placebo in the FeNO population and total population | Change from baseline to year 1 and year 2 in pre-BD FEV1, post-BD FEV1, FeNO levels, ACQ-7, pre-BD FEV1 % predicted and FVC Annualised severe exacerbation rate during 1-year period in the FeNO population and total populations Rate of change in post-BD FEV1 from week 8 to year 2 (post-BD FEV1 slope) in the total population |
| To evaluate the long-term effect of dupilumab in improving quality of life in year 1 and 2 compared with placebo in the FeNO population and total population | Change from baseline to year 1 and year 2 in AQLQ(S) in the FeNO population and total population | |
| To evaluate the long-term effect of dupilumab on preventing or slowing the rate of LFD by year 3 compared with placebo in the FeNO population and total population | Rate of change in post-BD FEV1 from week 8 to year 3 (post-BD FEV1 slope) in the FeNO population and total population | |
| Exploratory | To explore the effect of dupilumab on airway structural changes, small airways and gene expression profiling in the FeNO population (substudy in ∼200 patients) | Change from baseline to year 1, year 2 and year 3 in airway resistance at 5 Hz to airway resistance at 20 Hz measured by FOT and imaging parameters using high-resolution CT scans and mucus plugs in FeNO population Nasal brushing and secretion profiling, including transcriptomics and proteomics at baseline and weeks 8 to year 1, year 2 and year 3 in the FeNO population |
| Safety | To evaluate the safety of dupilumab | Incidence of TEAEs and SAEs Incidence of AESIs |
LFD: lung function decline; FeNO: fractional exhaled nitric oxide; BD: bronchodilator; FEV1: forced expiratory volume in 1 s; ACQ-7: seven-item Asthma Control Questionnaire; FVC: forced vital capacity; AQLQ(S): Asthma Quality of Life Questionnaire with standardised activities; FOT: forced oscillometry technique; CT: computed tomography; TEAEs: treatment-emergent adverse events; SAEs: serious adverse events; AESIs: adverse events of special interest.