Clinical trial NCT04502862: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2020-08-06
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Interim analysis for sample size re-estimation
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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 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.

Primary outcomes:
measure: Change From Baseline to Week 12 in Sleep Disturbance Score Using the Asthma Sleep Disturbance Questionnaire (ASDQ)
timeFrame: Baseline (Day -6 to Day 1) up to Week 12
Secondary outcomes:
measure: Change From Baseline to Week 12 on the Number of Nocturnal Awakenings (Sleep Diary)
timeFrame: Baseline (Day -6 to Day 1) up to Week 12
measure: Change From Baseline to Week 12 in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment 8a Scale
timeFrame: Baseline (Day 1) up to Week 12
measure: Change From Baseline to Week 12 in Sleep Quality (Sleep Diary)
timeFrame: Baseline (Day -6 to Day 1) up to Week 12
measure: Change From Baseline to Week 12 in Restorative Sleep (Sleep Diary)
timeFrame: Baseline (Day -6 to Day 1) up to Week 12
measure: Change From Baseline to Week 12 in Wake After Sleep Onset (WASO) (Sleep Diary)
timeFrame: Baseline (Day -6 to Day 1) up to Week 12
measure: Change From Baseline to Week 12 in WASO Based on Actigraphy Data
timeFrame: Baseline (Day -6 to Day 1) up to Week 12
measure: Change From Baseline to Week 12 in Asthma Daytime Symptom Diary (ADSD)
timeFrame: Baseline (Day -7 to Day -1) up to Week 12
measure: Change From Baseline to Week 12 in Asthma Nighttime Symptom Diary (ANSD)
timeFrame: Baseline (Day -6 to Day -1) up to Week 12
measure: Change From Baseline to Week 12 in Pre-Bronchodilator Forced Expiratory Volume (Pre-BD FEV1)
timeFrame: Baseline (Day 1) up to Week 12
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events Of Special Interest (TEAESIs)
timeFrame: From first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks
measure: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs
timeFrame: From first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Kern Allergy and Medical Research. Inc. Site Number : 8400003
state: California
city: Culver City
country: United States
facility: Todd Astor MD Site Number : 8400016
state: California
city: Los Angeles
country: United States
facility: Southern California Institute for Respiratory Diseases Site Number : 8400009
state: California
city: San Jose
country: United States
facility: Allergy & Asthma Associates of Santa Clara Valley Site Number : 8400001
state: California
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates, PC Site Number : 8400011
state: Colorado
city: Sarasota
country: United States
facility: Sarasota Clinical Research Site Number : 8400012
state: Florida
city: Owensboro
country: United States
facility: Allergy & Asthma Specialists, PSC Site Number : 8400004
state: Kentucky
city: Bellevue
country: United States
facility: The Asthma and Allergy Center Site Number : 8400010
state: Nebraska
city: Edmond
country: United States
facility: OK Clinical Research LLC Site Number : 8400005
state: Oklahoma
city: Medford
country: United States
facility: Velocity Clinical Research, Medford Site Number : 8400007
state: Oregon
city: Charleston
country: United States
facility: National Allergy and Asthma Research, LLC Site Number : 8400008
state: South Carolina
city: Boerne
country: United States
facility: TTS Research Site Number : 8400006
state: Texas
city: Caba
country: Argentina
facility: Investigational Site Number : 0320003
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number : 0320001
state: Buenos Aires
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320004
state: Santa Fe
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320005
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320002
city: Ajax
country: Canada
facility: Investigational Site Number : 1240012
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1240005
state: Ontario
city: Quebec
country: Canada
facility: Investigational Site Number : 1240009
city: Windsor
country: Canada
facility: Investigational Site Number : 1240008
city: Berlin
country: Germany
facility: Investigational Site Number : 2760002
city: Frankfurt am Main
country: Germany
facility: Investigational Site Number : 2760005
city: Hannover
country: Germany
facility: Investigational Site Number : 2760003
city: Koblenz
country: Germany
facility: Investigational Site Number : 2760001
city: Leipzig
country: Germany
facility: Investigational Site Number : 2760004
city: Lübeck
country: Germany
facility: Investigational Site Number : 2760006
city: Monserrato
country: Italy
facility: Investigational Site Number : 3800006
state: Cagliari
city: Orbassano
country: Italy
facility: Investigational Site Number : 3800001
state: Torino
city: Reggio Emilia
country: Italy
facility: Investigational Site Number : 3800005
city: Arnhem
country: Netherlands
facility: Investigational Site Number : 5280005
city: Breda
country: Netherlands
facility: Investigational Site Number : 5280001
city: Leeuwarden
country: Netherlands
facility: Investigational Site Number : 5280002
city: Aveiro
country: Portugal
facility: Investigational Site Number : 6200001
city: Guimarães
country: Portugal
facility: Investigational Site Number : 6200007
city: Lisboa
country: Portugal
facility: Investigational Site Number : 6200006
city: Matosinhos
country: Portugal
facility: Investigational Site Number : 6200003
city: Porto
country: Portugal
facility: Investigational Site Number : 6200004
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430001
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430002
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430006
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430005
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430007
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430004
city: Lugo / Lugo
country: Spain
facility: Investigational Site Number : 7240001
state: Galicia [Galicia]
city: Valencia
country: Spain
facility: Investigational Site Number : 7240002
state: Valenciana, Comunidad
city: Madrid
country: Spain
facility: Investigational Site Number : 7240005
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number : 8040002
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number : 8040006
city: Kharkiv
country: Ukraine
facility: Investigational Site Number : 8040003
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040008
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040007
city: Vinnytsya
country: Ukraine
facility: Investigational Site Number : 8040005
city: Cambridge
country: United Kingdom
facility: Investigational Site Number : 8260001
state: Cambridgeshire
city: London
country: United Kingdom
facility: Investigational Site Number : 8260002
state: London, City Of
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: