ATLAS is a multinational, phase III/IV, multicentre, randomised, double-blind, placebo-controlled and parallel-group study (figure 1 ). The study will include a screening and run-in period of 4 weeks (±1 week), a treatment period of 156 weeks and a follow-up period of up to 12 weeks.
Patients will be randomised (2:1) to receive a loading dose of dupilumab (two injections of 300 mg) subcutaneously on day 1, followed by 300 mg every 2 weeks or matching placebo (two injections of 2 mL) s.c. on day 1, followed by one placebo injection every 2 weeks. Randomisation will be stratified by inhaled corticosteroid (ICS) dose (medium versus high dose), FeNO (<35 ppb versus ≥35 ppb), baseline blood eosinophil count (<300 cells·μL−1versus ≥300 cells·μL−1) and region.
Post treatment period, the patients will be followed-up for 12 weeks or until the patients switch to commercialised dupilumab or any other therapies, whichever comes first.
All patients will be on stable maintenance therapy with medium-to-high dose ICS with a second controller medication (e.g. long-acting β2-adrenergic receptor agonists and leukotriene receptor antagonists) for ≥1 month before the screening visit and during the run-in period. A third controller is allowed, but not mandatory. Background asthma therapy would be maintained at a stable dose during the study screening and treatment period unless the patient experiences two exacerbations within 9 months, where the background ICS dose may be increased, or additional controllers may be added (figure 2 ).
Patients will be allowed to use rescue therapy (short-acting β-agonists) or single maintenance and reliever therapy throughout the study, as needed. Patients who experience frequent exacerbations will have the opportunity to receive additional therapy based on the rescue algorithm (figure 2 ).
Patients will be randomised (2:1) to receive a loading dose of dupilumab (two injections of 300 mg) subcutaneously on day 1, followed by 300 mg every 2 weeks or matching placebo (two injections of 2 mL) s.c. on day 1, followed by one placebo injection every 2 weeks. Randomisation will be stratified by inhaled corticosteroid (ICS) dose (medium versus high dose), FeNO (<35 ppb versus ≥35 ppb), baseline blood eosinophil count (<300 cells·μL−1versus ≥300 cells·μL−1) and region.
Post treatment period, the patients will be followed-up for 12 weeks or until the patients switch to commercialised dupilumab or any other therapies, whichever comes first.
All patients will be on stable maintenance therapy with medium-to-high dose ICS with a second controller medication (e.g. long-acting β2-adrenergic receptor agonists and leukotriene receptor antagonists) for ≥1 month before the screening visit and during the run-in period. A third controller is allowed, but not mandatory. Background asthma therapy would be maintained at a stable dose during the study screening and treatment period unless the patient experiences two exacerbations within 9 months, where the background ICS dose may be increased, or additional controllers may be added (
Patients will be allowed to use rescue therapy (short-acting β-agonists) or single maintenance and reliever therapy throughout the study, as needed. Patients who experience frequent exacerbations will have the opportunity to receive additional therapy based on the rescue algorithm (
