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

Asthma Clinical Trial

— MORPHEO  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04502862
• Other study ID #: LPS16677
• Secondary ID: U1111-1249-60542
• Status: Completed
• Phase: Phase 4
• Start date: August 10, 2020
• Est. completion date: November 10, 2023

Study information

• Verified date: January 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

To assess the effect of dupilumab on sleep

Secondary Objectives:

• To evaluate the effect of dupilumab on additional patient 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

Description:

Study duration per participant will be 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 switches to commercialized dupilumab (or other biologic product), whichever comes first.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 202
• Est. completion date: November 10, 2023
• Est. primary completion date: October 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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, 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.

Related Conditions & MeSH terms

• Asthma
• Dyssomnias
• Parasomnias

Intervention

Drug:
• SAR231893
Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous
• Placebo
Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320002	Buenos Aires
Argentina	Investigational Site Number : 0320001	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320003	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320004	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320005	Rosario	Santa Fe
Canada	Investigational Site Number : 1240012	Ajax	Ontario
Canada	Investigational Site Number : 1240009	Quebec
Canada	Investigational Site Number : 1240005	Toronto	Ontario
Canada	Investigational Site Number : 1240008	Windsor
Germany	Investigational Site Number : 2760002	Berlin
Germany	Investigational Site Number : 2760005	Frankfurt am Main
Germany	Investigational Site Number : 2760003	Hannover
Germany	Investigational Site Number : 2760001	Koblenz
Germany	Investigational Site Number : 2760004	Leipzig
Germany	Investigational Site Number : 2760006	Lübeck
Italy	Investigational Site Number : 3800006	Monserrato	Cagliari
Italy	Investigational Site Number : 3800001	Orbassano	Torino
Italy	Investigational Site Number : 3800005	Reggio Emilia
Netherlands	Investigational Site Number : 5280005	Arnhem
Netherlands	Investigational Site Number : 5280001	Breda
Netherlands	Investigational Site Number : 5280002	Leeuwarden
Portugal	Investigational Site Number : 6200001	Aveiro
Portugal	Investigational Site Number : 6200007	Guimarães
Portugal	Investigational Site Number : 6200006	Lisboa
Portugal	Investigational Site Number : 6200003	Matosinhos
Portugal	Investigational Site Number : 6200004	Porto
Russian Federation	Investigational Site Number : 6430001	Moscow
Russian Federation	Investigational Site Number : 6430002	Moscow
Russian Federation	Investigational Site Number : 6430005	Moscow
Russian Federation	Investigational Site Number : 6430006	Moscow
Russian Federation	Investigational Site Number : 6430004	St-Petersburg
Russian Federation	Investigational Site Number : 6430007	St-Petersburg
Spain	Investigational Site Number : 7240003	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240001	Lugo / Lugo	Galicia [Galicia]
Spain	Investigational Site Number : 7240005	Madrid
Spain	Investigational Site Number : 7240006	Pozuelo De Alarcón	Madrid
Spain	Investigational Site Number : 7240002	Valencia	Valenciana, Comunidad
Ukraine	Investigational Site Number : 8040002	Ivano-Frankivsk
Ukraine	Investigational Site Number : 8040006	Ivano-Frankivsk
Ukraine	Investigational Site Number : 8040003	Kharkiv
Ukraine	Investigational Site Number : 8040007	Kyiv
Ukraine	Investigational Site Number : 8040008	Kyiv
Ukraine	Investigational Site Number : 8040005	Vinnytsya
United Kingdom	Investigational Site Number : 8260001	Cambridge	Cambridgeshire
United Kingdom	Investigational Site Number : 8260002	London	London, City Of
United States	Kern Allergy and Medical Research. Inc. Site Number : 8400003	Bakersfield	California
United States	The Asthma and Allergy Center Site Number : 8400010	Bellevue	Nebraska
United States	TTS Research Site Number : 8400006	Boerne	Texas
United States	National Allergy and Asthma Research, LLC Site Number : 8400008	Charleston	South Carolina
United States	Asthma and Allergy Associates, PC Site Number : 8400011	Colorado Springs	Colorado
United States	Todd Astor MD Site Number : 8400016	Culver City	California
United States	OK Clinical Research LLC Site Number : 8400005	Edmond	Oklahoma
United States	Southern California Institute for Respiratory Diseases Site Number : 8400009	Los Angeles	California
United States	Velocity Clinical Research, Medford Site Number : 8400007	Medford	Oregon
United States	Allergy & Asthma Specialists, PSC Site Number : 8400004	Owensboro	Kentucky
United States	Allergy & Asthma Associates of Santa Clara Valley Site Number : 8400001	San Jose	California
United States	Sarasota Clinical Research Site Number : 8400012	Sarasota	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Germany,  Italy,  Netherlands,  Portugal,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in sleep disturbance score in Asthma Sleep Disturbance Questionnaire	Change from baseline to Week 12 in sleep disturbance score using the Asthma Sleep Disturbance Questionnaire	Baseline to Week 12
Secondary	Change in the number of nocturnal awakenings in Sleep Diary	Change from baseline to Week 12 in the number of nocturnal awakenings as recorded in Sleep Diary	Baseline to Week 12
Secondary	Change in PROMIS sleep-related impairment assessment	Change from baseline to Week 12 in Patient-Reported Outcomes Measurement Information System (PROMIS) sleep-related impairment 8a scale	Baseline to Week 12
Secondary	Change in sleep quality in Sleep Diary	Change from baseline to Week 12 in sleep quality (Sleep Diary)	Baseline to Week 12
Secondary	Change in restorative sleep in Sleep Diary	Change from baseline to Week 12 in restorative sleep (Sleep Diary)	Baseline to Week 12
Secondary	Change in WASO in Sleep Diary	Change from baseline to Week 12 in wake after sleep onset (WASO) (Sleep Diary)	Baseline to Week 12
Secondary	Change in WASO (actigraphy data)	Change from baseline to Week 12 in WASO based on actigraphy data	Baseline to Week 12
Secondary	Change in daytime and nighttime asthma symptoms in Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD)	Change from baseline to Week 12 in Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD)	Baseline to Week 12
Secondary	Change in pre-bronchodilator (BD) FEV1	Change from baseline to Week 12 in prebronchodilator forced expiratory volume in 1 second (pre-BD FEV1)	Baseline to Week 12
Secondary	Incidence of adverse events	Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and adverse events of special interest (AESI), including clinically significant changes in vital signs considered to be adverse events	Baseline up to Week 24