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

-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

-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 periodic limb movement disorder
-Chronic treatment with OCS for more than 2 weeks before screening Visit 1
- Participant taking sedative, anxiolytic, or hypnotic treatments, including
melatonin, within 3 months
before randomization
-Participant taking systemic sedative antihistamines (excluding newer
generations of
antihistamines) or theophylline
-Current treatment with antidepressants, lipophilic beta blockers, clonidine,
opioids, or other
medications known to interfere with sleep and may confound the study
assessments, as determined
by the Investigator
-Participant who has taken biologic therapy (including dupilumab)/systemic
immunosuppressant to treat inflammatory disease or autoimmune disease (eg,
rheumatoid
arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus
erythematosus, multiple sclerosis, etc) within 2 months or 5 half-lives before
screening
Visit 1, whichever is longer
-Treatment with live (attenuated) vaccine within 4 weeks before screening Visit
1
NOTE: For participants who have vaccination with live, attenuated vaccines
planned
during the course of the study (based on national vaccination schedule/local
guidelines), it
will be determined, after consultation with a physician, whether the
administration of
vaccine can be postponed until after the end of the study, (i.e. after the 12
week follow-up
period off-treatment or until the participant switches to commercialized
dupilumab or other
biologic product, whichever comes first), or preponed to before the start of
the study
without compromising the health of the participant:
* Participant for whom administration of live (attenuated) vaccine can be safely
postponed would be eligible to enroll into the study.
* Participant who have their vaccination preponed can enroll in the study only
after a gap
of 4 weeks following administration of the vaccine.