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

NCT ID: NCT04502862

Last Updated: 2024-12-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 202 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-10
• Study Completion Date: 2023-11-10

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dupilumab

Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.

Group Type: EXPERIMENTAL

SAR231893

Intervention Type: DRUG

Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous

Placebo

Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous

Interventions

SAR231893

Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous

Intervention Type: DRUG

Placebo

Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous

Intervention Type: DRUG

Other Intervention Names

Dupixent

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
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Kern Allergy and Medical Research. Inc. Site Number : 8400003

Bakersfield, California, United States

Todd Astor MD Site Number : 8400016

Culver City, California, United States

Southern California Institute for Respiratory Diseases Site Number : 8400009

Los Angeles, California, United States

Allergy & Asthma Associates of Santa Clara Valley Site Number : 8400001

San Jose, California, United States

Asthma and Allergy Associates, PC Site Number : 8400011

Colorado Springs, Colorado, United States

Sarasota Clinical Research Site Number : 8400012

Sarasota, Florida, United States

Allergy & Asthma Specialists, PSC Site Number : 8400004

Owensboro, Kentucky, United States

The Asthma and Allergy Center Site Number : 8400010

Bellevue, Nebraska, United States

OK Clinical Research LLC Site Number : 8400005

Edmond, Oklahoma, United States

Velocity Clinical Research, Medford Site Number : 8400007

Medford, Oregon, United States

National Allergy and Asthma Research, LLC Site Number : 8400008

Charleston, South Carolina, United States

TTS Research Site Number : 8400006

Boerne, Texas, United States

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

Investigational Site Number : 1240012

Ajax, Ontario, Canada

Investigational Site Number : 1240005

Toronto, Ontario, Canada

Investigational Site Number : 1240009

Québec, , Canada

Investigational Site Number : 1240008

Windsor, , Canada

Investigational Site Number : 2760002

Berlin, , Germany

Investigational Site Number : 2760005

Frankfurt am Main, , Germany

Investigational Site Number : 2760003

Hanover, , Germany

Investigational Site Number : 2760001

Koblenz, , Germany

Investigational Site Number : 2760004

Leipzig, , Germany

Investigational Site Number : 2760006

Lübeck, , Germany

Investigational Site Number : 3800006

Monserrato, Cagliari, Italy

Investigational Site Number : 3800001

Orbassano, Torino, Italy

Investigational Site Number : 3800005

Reggio Emilia, , Italy

Investigational Site Number : 5280005

Arnhem, , Netherlands

Investigational Site Number : 5280001

Breda, , Netherlands

Investigational Site Number : 5280002

Leeuwarden, , Netherlands

Investigational Site Number : 6200001

Aveiro, , Portugal

Investigational Site Number : 6200007

Guimarães, , Portugal

Investigational Site Number : 6200006

Lisbon, , Portugal

Investigational Site Number : 6200003

Matosinhos Municipality, , Portugal

Investigational Site Number : 6200004

Porto, , Portugal

Investigational Site Number : 6430001

Moscow, , Russia

Investigational Site Number : 6430002

Moscow, , Russia

Investigational Site Number : 6430006

Moscow, , Russia

Investigational Site Number : 6430005

Moscow, , Russia

Investigational Site Number : 6430007

Saint Petersburg, , Russia

Investigational Site Number : 6430004

Saint Petersburg, , Russia

Investigational Site Number : 7240001

Lugo / Lugo, Galicia [Galicia], Spain

Investigational Site Number : 7240002

Valencia, Valenciana, Comunidad, Spain

Investigational Site Number : 7240005

Madrid, , Spain

Investigational Site Number : 8040002

Ivano-Frankivsk, , Ukraine

Investigational Site Number : 8040006

Ivano-Frankivsk, , Ukraine

Investigational Site Number : 8040003

Kharkiv, , Ukraine

Investigational Site Number : 8040008

Kyiv, , Ukraine

Investigational Site Number : 8040007

Kyiv, , Ukraine

Investigational Site Number : 8040005

Vinnytsia, , Ukraine

Investigational Site Number : 8260001

Cambridge, Cambridgeshire, United Kingdom

Investigational Site Number : 8260002

London, London, City of, United Kingdom

Countries

United States; Argentina; Canada; Germany; Italy; Netherlands; Portugal; Russia; Spain; Ukraine; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://sanofi.trialsummaries.com/Study/StudyDetails?id=25288&tenant=MT_SNY_9011

LPS16677 Plain language Results Summary

Other Identifiers

U1111-1249-6054

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-001217-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LPS16677

Identifier Type: -

Identifier Source: org_study_id