Resumen

Primary Objective: To assess the effect of dupilumab on sleep Secondary Objectives: * To evaluate the effect of dupilumab on additional participant reported sleep outcomes * To evaluate the effect of dupilumab on objective sleep assessment * To evaluate the effect of dupilumab on asthma symptoms * To evaluate the effect of dupilumab on lung function * To evaluate the safety of dupilumab

Descripción detallada

Study duration per participant was approximately 16 weeks and up to 29 weeks including up to 5 weeks screening period, a 12-week treatment period and up to 12 weeks post-treatment follow-up period or until the participant switched to commercialized dupilumab (or other biologic product), whichever came first.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 65 YearsSexo: ALL

Criterios de inclusión

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
Weekly average nocturnal awakenings due to asthma symptoms in the week prior to screening Visit 1 is ≥1

Criterios de exclusión

History of human immunodeficiency (HIV) infection or positive HIV test at screening Visit 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
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 oral corticosteroid (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
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ubicaciones

Investigational Site Number : 0320003

CABA, Buenos Aires, Argentina

Investigational Site Number : 0320001

CABA, Buenos Aires, Argentina

Investigational Site Number : 0320004

Rosario, Santa Fe Province, Argentina

Investigational Site Number : 0320005

Rosario, Santa Fe Province, Argentina

Investigational Site Number : 0320002

Buenos Aires, Argentina

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