A Phase 4, Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study of the Effect of Dupilumab on Sleep Disturbance in Patients With Uncontrolled Persistent Asthma

Inclusion Criteria

• Physician diagnosis of asthma based on the Global Initiative for Asthma (GINA) 2020 Guidelines for ≥12 months treated with medium to high dose inhaled corticosteroid (ICS) and a second controller (ie, long-acting beta agonist, leukotriene receptor antagonist). A third controller is allowed but not mandatory. The dose regimen should be stable for at least 1 month before the study and during the screening period
• History of at least one severe asthma exacerbation within 1 year prior to screening. Severe exacerbation is defined as deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with systemic steroids (oral or injectable)
• Eosinophils ≥150 cells/μL and fractional exhaled nitric oxide (FeNO) ≥25 ppb during screening, prior to randomization
• NOTES:
• Historical values of blood eosinophil count meeting the eligibility criterion measured within 6 months prior to screening Visit 1 in the absence of oral corticosteroid (OCS) treatment are allowed
• FeNO value to be checked for eligibility at Visit 2 as well
• Asthma control questionnaire (ACQ)-5 ≥2.5 at screening Visit 1 and Visit 2, prior to randomization
• Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) ≤ 80% of predicted normal during screening and at Visit 2, prior to randomization
• Exhibit bronchodilator reversibility (≥12% and 200 mL improvement in FEV1 post short-acting beta agonist administration) during screening period, prior to randomization, unless reversibility test meeting the inclusion criteria was done within 6 months prior to screening Visit 1
• Weekly average nocturnal awakenings due to asthma symptoms in the week prior to screening Visit 1 is ≥1

Exclusion Criteria

• Current smoker
• Former smoker for 10 years with a smoking history of >10 pack-years
• Severe asthma exacerbation during screening, prior to randomization
• History or clinical evidence of chronic obstructive pulmonary disease (COPD) including Asthma-COPD Overlap Syndrome (ACOS) or any other significant lung disease (eg, lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, Churg-Strauss Syndrome)
• History of or current evidence of clinically significant non-respiratory diseases that in the opinion of the investigator may interfere with the aims of the study or put the participant at undue risk
• Active tuberculosis (TB) or non-tuberculous mycobacterial infection, or a history of incompletely treated TB will be excluded unless it is well documented by a specialist that the participant has been adequately treated and can now start treatment with a biologic agent, in the medical judgment of the Investigator and/or infectious disease specialist. Tuberculosis testing would be performed on a country by country basis, according to local guidelines if required by Regulatory Authorities or ethics boards
• Diagnosed active endoparasitic infection; suspected or high risk of endoparasitic infection, unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization
• History of human immunodeficiency (HIV) infection or positive HIV test at screening Visit 1
• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before screening
• Known or suspected immunodeficiency including history of invasive opportunistic infections, despite infection resolution
• Current evidence of clinically significant oncological disease
• History of systemic hypersensitivity or anaphylaxis to any biologic therapy
• Severe uncontrolled depression
• Sleep disturbances not related to asthma, including sleep apnea, hypersomnia, or insomnia secondary to chronic pain, atopic dermatitis (AD), COPD or other conditions
• Participant who works night shift (ie, any work between 8 pm and 6 am)
• Erratic sleep habits, as determined by the Investigator
• Restless leg syndrome or periodi