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

NCT04502862 | Completed Phase 4 Results FDA Drug

• 3 other identifiers: LPS16677U1111-1249-60542020-001217-20
• Study Type: interventional
• Target: 202
• Locations: 11 countries
• Sites: 55

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

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 12 in Sleep Disturbance Score Using the Asthma Sleep Disturbance Questionnaire (ASDQ)

  The ASDQ is a participant-reported outcome (PRO) measure designed to assess the impact of asthma on participants' sleep. Participants were instructed to record the severity of the disturbance of their sleep due to asthma as: 0 = slept through the night, no asthma symptoms; 1 = slept well, no night time awakenings because of asthma, but some asthma symptoms in the morning; 2 = woke up once because of asthma (may or may not include early awakening); 3 = woke up several times because of asthma (may or may not include early awakening) and 4 = bad night, awake most of the night because of asthma. The participants recorded their sleep disturbance in an electronic diary, once a day upon awakening. Total scores ranges between 0 to 4 with 0 indicating no impact of asthma on sleep and 4 indicating higher impact of asthma on sleep. Higher scores indicated worse outcomes. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.

  Baseline (Day -6 to Day 1) up to Week 12

Secondary Outcomes (11)

• Change From Baseline to Week 12 on the Number of Nocturnal Awakenings (Sleep Diary)

  Baseline (Day -6 to Day 1) up to Week 12

• Change From Baseline to Week 12 in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment 8a Scale

  Baseline (Day 1) up to Week 12

• Change From Baseline to Week 12 in Sleep Quality (Sleep Diary)

  Baseline (Day -6 to Day 1) up to Week 12

• Change From Baseline to Week 12 in Restorative Sleep (Sleep Diary)

  Baseline (Day -6 to Day 1) up to Week 12

• Change From Baseline to Week 12 in Wake After Sleep Onset (WASO) (Sleep Diary)

  Baseline (Day -6 to Day 1) up to Week 12

Study Arms (2)

Dupilumab

EXPERIMENTAL

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.

Drug: SAR231893

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

SAR231893 DRUG

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

Also known as: Dupixent

Dupilumab

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (55)

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

Bakersfield, California, 93301, United States

Location

Todd Astor MD Site Number : 8400016

Culver City, California, 90230, United States

Location

Southern California Institute for Respiratory Diseases Site Number : 8400009

Los Angeles, California, 90048, United States

Location

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

San Jose, California, 95117, United States

Location

Asthma and Allergy Associates, PC Site Number : 8400011

Colorado Springs, Colorado, 80907, United States

Location

Sarasota Clinical Research Site Number : 8400012

Sarasota, Florida, 34239, United States

Location

Allergy & Asthma Specialists, PSC Site Number : 8400004

Owensboro, Kentucky, 42301, United States

Location

The Asthma and Allergy Center Site Number : 8400010

Bellevue, Nebraska, 68123, United States

Location

OK Clinical Research LLC Site Number : 8400005

Edmond, Oklahoma, 73034, United States

Location

Velocity Clinical Research, Medford Site Number : 8400007

Medford, Oregon, 97504, United States

Location

National Allergy and Asthma Research, LLC Site Number : 8400008

Charleston, South Carolina, 29407, United States

Location

TTS Research Site Number : 8400006

Boerne, Texas, 78006, United States

Location

Investigational Site Number : 0320003

CABA, Buenos Aires, C1414AIF, Argentina

Location

Investigational Site Number : 0320001

CABA, Buenos Aires, C1425FVH, Argentina

Location

Investigational Site Number : 0320004

Rosario, Santa Fe Province, S2000DEJ, Argentina

Location

Investigational Site Number : 0320005

Rosario, Santa Fe Province, S2002OJP, Argentina

Location

Investigational Site Number : 0320002

Buenos Aires, C1121ABE, Argentina

Location

Investigational Site Number : 1240012

Ajax, Ontario, L1S 2J5, Canada

Location

Investigational Site Number : 1240005

Toronto, Ontario, M9V 4B4, Canada

Location

Investigational Site Number : 1240009

Québec, G1G 3Y8, Canada

Location

Investigational Site Number : 1240008

Windsor, N8X 5A6, Canada

Location

Investigational Site Number : 2760002

Berlin, 10787, Germany

Location

Investigational Site Number : 2760005

Frankfurt am Main, 60596, Germany

Location

Investigational Site Number : 2760003

Hanover, 30173, Germany

Location

Investigational Site Number : 2760001

Koblenz, 56068, Germany

Location

Investigational Site Number : 2760004

Leipzig, 04347, Germany

Location

Investigational Site Number : 2760006

Lübeck, 23552, Germany

Location

Investigational Site Number : 3800006

Monserrato, Cagliari, 09042, Italy

Location

Investigational Site Number : 3800001

Orbassano, Torino, 10043, Italy

Location

Investigational Site Number : 3800005

Reggio Emilia, 42123, Italy

Location

Investigational Site Number : 5280005

Arnhem, 6815 AD, Netherlands

Location

Investigational Site Number : 5280001

Breda, 4818 CK, Netherlands

Location

Investigational Site Number : 5280002

Leeuwarden, 8934 AD, Netherlands

Location

Investigational Site Number : 6200001

Aveiro, 3810-501, Portugal

Location

Investigational Site Number : 6200007

Guimarães, 4810-061, Portugal

Location

Investigational Site Number : 6200006

Lisbon, 1769, Portugal

Location

Investigational Site Number : 6200003

Matosinhos Municipality, 4464-513, Portugal

Location

Investigational Site Number : 6200004

Porto, 4202-451, Portugal

Location

Investigational Site Number : 6430001

Moscow, 115093, Russia

Location

Investigational Site Number : 6430002

Moscow, 115280, Russia

Location

Investigational Site Number : 6430006

Moscow, 115478, Russia

Location

Investigational Site Number : 6430005

Moscow, 117546, Russia

Location

Investigational Site Number : 6430007

Saint Petersburg, 193231, Russia

Location

Investigational Site Number : 6430004

Saint Petersburg, 194354, Russia

Location

Investigational Site Number : 7240001

Lugo / Lugo, Galicia [Galicia], 27003, Spain

Location

Investigational Site Number : 7240002

Valencia, Valenciana, Comunidad, 46017, Spain

Location

Investigational Site Number : 7240005

Madrid, 28006, Spain

Location

Investigational Site Number : 8040002

Ivano-Frankivsk, 76018, Ukraine

Location

Investigational Site Number : 8040006

Ivano-Frankivsk, 76018, Ukraine

Location

Investigational Site Number : 8040003

Kharkiv, 61166, Ukraine

Location

Investigational Site Number : 8040008

Kyiv, 01023, Ukraine

Location

Investigational Site Number : 8040007

Kyiv, 01033, Ukraine

Location

Investigational Site Number : 8040005

Vinnytsia, 21001, Ukraine

Location

Investigational Site Number : 8260001

Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom

Location

Investigational Site Number : 8260002

London, London, City of, EC1M 6BQ, United Kingdom

Location

Related Links

• LPS16677 Plain language Results Summary

MeSH Terms

Conditions

Asthma

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610 ext 6#

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Interim analysis for sample size re-estimation

Study Record Dates

• First Submitted: August 4, 2020
• First Posted: August 6, 2020
• Study Start: August 10, 2020
• Primary Completion: October 3, 2023
• Study Completion: November 10, 2023
• Last Updated: December 6, 2024
• Results First Posted: November 26, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share

Locations

ES (3); UA (6); PT (5); DE (6); IT (3); RU (6); GB (2); CA (4); US (12); NL (3); AR (5)