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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1249-6054 | Registry Identifier | ICTRP | |
| 2020-001217-20 | EudraCT Number |
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| Name | Class |
|---|---|
| Regeneron Pharmaceuticals | INDUSTRY |
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Primary Objective:
To assess the effect of dupilumab on sleep
Secondary Objectives:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SAR231893 | Drug | Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 12 on the Number of Nocturnal Awakenings (Sleep Diary) | Sleep diary is used to assess adult sleep disturbance due to asthma. Number of nocturnal awakenings was determined based on answer on question from sleep diary: "Approximately how many times did you wake up last night (not including when you woke up for the day today)?" Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1. |
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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
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
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Sciences & Operations | Sanofi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kern Allergy and Medical Research. Inc. Site Number : 8400003 | Bakersfield | California | 93301 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42370853 | Derived | Maspero JF, Gupta A, Schmidt O, Perez de Llano LA, Martinez Moragon E, Knolle M, Pfeffer PE, Ricciardolo FL, van der Sar-van der Brugge S, Lopes C, Ostrovskyy M, Dobrianskyi D, Cole J, Wachtel A, Zhang M, Berthou B, Gall R, Awad H. Effect of Dupilumab on Sleep Disturbance in Patients With Uncontrolled Moderate-to-Severe Asthma, Type 2 Inflammation, and Nocturnal Awakenings: The MORPHEO Randomized Controlled Trial. J Investig Allergol Clin Immunol. 2026 Jun 29:0. doi: 10.18176/jiaci.1160. Online ahead of print. |
| Label | URL |
|---|---|
| LPS16677 Plain language Results Summary | View source |
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Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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A total of 202 participants were randomized in a ratio of 1:1 to receive dupilumab or matching placebo every 2 weeks (Q2W) for 12 weeks.
The study was conducted at 52 centers in 11 countries. A total of 397 participants were screened between 10 August 2020 to 30 May 2023, of which 195 participants were screen failures. Screen failures were mainly due to not meeting the eligibility criteria.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dupilumab 200 mg Q2W | Participants received a loading dose of 400 milligrams (mg) of dupilumab (2 injections × 200 mg) subcutaneous (SC) on Day 1, followed by 200 mg Q2W for 12 weeks. |
| FG001 | Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 22, 2022 | Sep 30, 2024 |
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Interim analysis for sample size re-estimation
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| Placebo | Drug | Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous |
|
| 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 | PROMIS sleep-related impairment eight-term 8a scale was administered to assess impact of sleep-related impairment during waking hours. The questionnaire focuses on self-reported perceptions of alertness, sleepiness, and tiredness during usual waking hours, and perceived functional impairments during wakefulness associated with sleep problems or impaired alertness. It assesses sleep-related impairment over the past 7 days. Each item is rated on a 5-point scale (1 = not at all; 2 = a little bit; 3 = somewhat; 4 = quite a bit; and 5 = very much) with a raw score from 8 to 40 with higher scores indicating greater sleep impairment. PROMIS T-score is presented which rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. Possible range for T-score=30 to 80; higher scores=greater severity of sleep impairment. Baseline=last available valid (non-missing) value up to and including the day of first dose of investigational medicinal product (IMP). | Baseline (Day 1) up to Week 12 |
| Change From Baseline to Week 12 in Sleep Quality (Sleep Diary) | Sleep diary is used to assess adult sleep disturbance due to asthma. Sleep quality was assessed on a 11-point scale which ranged from 0 (worst possible sleep) to 10 (best possible sleep); higher scores indicated better 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 |
| Change From Baseline to Week 12 in Restorative Sleep (Sleep Diary) | Sleep Diary is used to assess adult sleep disturbance due to asthma. Question about restorative sleep asks participants to recall "when they got up for the day today". Restorative sleep was assessed on a 11-point scale which ranged from 0 (worst possible sleep) to 10 (best possible sleep); higher scores indicated better 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 |
| Change From Baseline to Week 12 in Wake After Sleep Onset (WASO) (Sleep Diary) | Sleep Diary is used to assess adult sleep disturbance due to asthma. WASO was calculated as time awake after initial sleep onset but before the final awakening. 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 |
| Change From Baseline to Week 12 in WASO Based on Actigraphy Data | Wrist actigraphy is a procedure that records and integrates occurrence and degree of limb movement activity over an extended recording period. The signals generated by wrist movement are sensed by a tiny microcomputer contained within watch and translated into activity counts. Algorithms have been developed to translate these activity counts or "epochs" (or "periods") that correspond to times when a person is likely to be asleep or wake. Actigraph was worn on wrist of non-dominant hand to provide estimates of duration, timing and patterns of sleep in study participants. After the watch data were scored by a selected expert center, a number of summary measurements were generated for each participant, including WASO. 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 |
| Change From Baseline to Week 12 in Asthma Daytime Symptom Diary (ADSD) | The ADSD is a PRO measure designed to measure asthma symptoms in adult and adolescent (12 years of age and older) participants diagnosed with mild to severe asthma. ADSD assesses asthma severity based on participant self-report of asthma core symptoms, i.e., difficulty breathing, wheezing, shortness of breath, chest tightness, chest pain, and cough. Participants were asked to complete the ADSD every night before they go to bed, thinking about their asthma symptoms today, from when they got up this morning until now. ADSD is composed of 6 items rated using an 11-point NRS that ranges from 0 = None to 10 = as bad as you can imagine. The total score was calculated by averaging all 6 items and therefore the score ranged from 0 to 10. Higher scores indicated worse outcomes. Baseline value was average of the data from Day -7 to Day -1. | Baseline (Day -7 to Day -1) up to Week 12 |
| Change From Baseline to Week 12 in Asthma Nighttime Symptom Diary (ANSD) | The ANSD is a PRO measure designed to measure asthma symptoms in adult and adolescent (12 years of age and older) participants diagnosed with mild to severe asthma. ANSD assesses asthma severity based on participant self-report of asthma core symptoms, i.e., difficulty breathing, wheezing, shortness of breath, chest tightness, chest pain, and cough. Participants were asked to complete the ANSD when getting up, thinking about their asthma symptoms last night from when they went to bed until now. ANSD is composed of 6 items rated using an 11-point NRS that ranges from 0 = None to 10 = as bad as you can imagine. The total score was calculated by averaging all 6 items and therefore the score ranged from 0 to 10. Higher scores indicated worse outcomes. Baseline value was average of the data from Day -6 to Day -1. | Baseline (Day -6 to Day -1) up to Week 12 |
| Change From Baseline to Week 12 in Pre-Bronchodilator Forced Expiratory Volume (Pre-BD FEV1) | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. For pre-BD FEV1, spirometry was performed before IMP administration and after withholding the standard of care asthma treatment which was verified before performing the measurements. Baseline was defined as the last available valid (non-missing) value up to and including the day of first dose of IMP. | Baseline (Day 1) up to Week 12 |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events Of Special Interest (TEAESIs) | AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs: AEs that developed or worsened or became serious during TEAE period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 98 days or until participant switches to commercialized dupilumab or other biologics. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. AESI: AE (serious or nonserious) of scientific and medical concern specific to Sponsor's product or program, for which ongoing monitoring and immediate notification by Investigator to Sponsor is required. | From first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks |
| Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs | Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and weight. Criteria for PCSA: SBP: ≤95 millimeters of mercury (mmHg) and decrease from baseline ≥20 mmHg, ≥160 mmHg and increase from baseline ≥20 mmHg; DBP: ≤45 mmHg and decrease from baseline ≥10 mmHg, ≥ 110 mmHg and increase from baseline ≥ 10 mmHg; HR: ≤ 50 beats per minute (bpm) and decrease from baseline ≥ 20 bpm, ≥120 bpm and increase from baseline ≥ 20 bpm; Weight: ≥ 5% increase from baseline, ≥5% decrease from baseline. | From first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks |
| Todd Astor MD Site Number : 8400016 |
| Culver City |
| California |
| 90230 |
| United States |
| Southern California Institute for Respiratory Diseases Site Number : 8400009 | Los Angeles | California | 90048 | United States |
| Allergy & Asthma Associates of Santa Clara Valley Site Number : 8400001 | San Jose | California | 95117 | United States |
| Asthma and Allergy Associates, PC Site Number : 8400011 | Colorado Springs | Colorado | 80907 | United States |
| Sarasota Clinical Research Site Number : 8400012 | Sarasota | Florida | 34239 | United States |
| Allergy & Asthma Specialists, PSC Site Number : 8400004 | Owensboro | Kentucky | 42301 | United States |
| The Asthma and Allergy Center Site Number : 8400010 | Bellevue | Nebraska | 68123 | United States |
| OK Clinical Research LLC Site Number : 8400005 | Edmond | Oklahoma | 73034 | United States |
| Velocity Clinical Research, Medford Site Number : 8400007 | Medford | Oregon | 97504 | United States |
| National Allergy and Asthma Research, LLC Site Number : 8400008 | Charleston | South Carolina | 29407 | United States |
| TTS Research Site Number : 8400006 | Boerne | Texas | 78006 | United States |
| Investigational Site Number : 0320003 | CABA | Buenos Aires | C1414AIF | Argentina |
| Investigational Site Number : 0320001 | CABA | Buenos Aires | C1425FVH | Argentina |
| Investigational Site Number : 0320004 | Rosario | Santa Fe Province | S2000DEJ | Argentina |
| Investigational Site Number : 0320005 | Rosario | Santa Fe Province | S2002OJP | Argentina |
| Investigational Site Number : 0320002 | Buenos Aires | C1121ABE | Argentina |
| Investigational Site Number : 1240012 | Ajax | Ontario | L1S 2J5 | Canada |
| Investigational Site Number : 1240005 | Toronto | Ontario | M9V 4B4 | Canada |
| Investigational Site Number : 1240009 | Québec | G1G 3Y8 | Canada |
| Investigational Site Number : 1240008 | Windsor | N8X 5A6 | Canada |
| Investigational Site Number : 2760002 | Berlin | 10787 | Germany |
| Investigational Site Number : 2760005 | Frankfurt am Main | 60596 | Germany |
| Investigational Site Number : 2760003 | Hanover | 30173 | Germany |
| Investigational Site Number : 2760001 | Koblenz | 56068 | Germany |
| Investigational Site Number : 2760004 | Leipzig | 04347 | Germany |
| Investigational Site Number : 2760006 | Lübeck | 23552 | Germany |
| Investigational Site Number : 3800006 | Monserrato | Cagliari | 09042 | Italy |
| Investigational Site Number : 3800001 | Orbassano | Torino | 10043 | Italy |
| Investigational Site Number : 3800005 | Reggio Emilia | 42123 | Italy |
| Investigational Site Number : 5280005 | Arnhem | 6815 AD | Netherlands |
| Investigational Site Number : 5280001 | Breda | 4818 CK | Netherlands |
| Investigational Site Number : 5280002 | Leeuwarden | 8934 AD | Netherlands |
| Investigational Site Number : 6200001 | Aveiro | 3810-501 | Portugal |
| Investigational Site Number : 6200007 | Guimarães | 4810-061 | Portugal |
| Investigational Site Number : 6200006 | Lisbon | 1769 | Portugal |
| Investigational Site Number : 6200003 | Matosinhos Municipality | 4464-513 | Portugal |
| Investigational Site Number : 6200004 | Porto | 4202-451 | Portugal |
| Investigational Site Number : 6430001 | Moscow | 115093 | Russia |
| Investigational Site Number : 6430002 | Moscow | 115280 | Russia |
| Investigational Site Number : 6430006 | Moscow | 115478 | Russia |
| Investigational Site Number : 6430005 | Moscow | 117546 | Russia |
| Investigational Site Number : 6430007 | Saint Petersburg | 193231 | Russia |
| Investigational Site Number : 6430004 | Saint Petersburg | 194354 | Russia |
| Investigational Site Number : 7240001 | Lugo / Lugo | Galicia [Galicia] | 27003 | Spain |
| Investigational Site Number : 7240002 | Valencia | Valenciana, Comunidad | 46017 | Spain |
| Investigational Site Number : 7240005 | Madrid | 28006 | Spain |
| Investigational Site Number : 8040002 | Ivano-Frankivsk | 76018 | Ukraine |
| Investigational Site Number : 8040006 | Ivano-Frankivsk | 76018 | Ukraine |
| Investigational Site Number : 8040003 | Kharkiv | 61166 | Ukraine |
| Investigational Site Number : 8040008 | Kyiv | 01023 | Ukraine |
| Investigational Site Number : 8040007 | Kyiv | 01033 | Ukraine |
| Investigational Site Number : 8040005 | Vinnytsia | 21001 | Ukraine |
| Investigational Site Number : 8260001 | Cambridge | Cambridgeshire | CB2 2QQ | United Kingdom |
| Investigational Site Number : 8260002 | London | London, City of | EC1M 6BQ | United Kingdom |
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.
| Randomized and Treated |
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| COMPLETED |
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| NOT COMPLETED |
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The Intent-to-treat (ITT) analysis set consisted of all randomized participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Dupilumab 200 mg Q2W | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Sleep Disturbance Score | Sleep disturbance score was assessed by Asthma Sleep Disturbance Questionnaire (ASDQ). Participants recorded severity of disturbance of sleep due to asthma as: 0 = slept through 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; 3 = woke up several times because of asthma and 4 = bad night, awake most of the night because of asthma. Total scores ranges between 0 (no impact of asthma on sleep) and 4 (higher impact of asthma on sleep). Higher scores indicated worse outcomes. | Only those participants with data available at baseline are reported. | Mean | Standard Deviation | Score on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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. | The ITT for primary endpoint (ITTp) analysis set consisted of all ITT participants excluding those who used the original version of sleep disturbance questionnaire at baseline and/or post-baseline included in the mixed effect model for repeated measures (MMRM) model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline (Day -6 to Day 1) up to Week 12 |
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| Secondary | Change From Baseline to Week 12 on the Number of Nocturnal Awakenings (Sleep Diary) | Sleep diary is used to assess adult sleep disturbance due to asthma. Number of nocturnal awakenings was determined based on answer on question from sleep diary: "Approximately how many times did you wake up last night (not including when you woke up for the day today)?" Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1. | The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported. | Posted | Least Squares Mean | Standard Error | Number of nocturnal awakenings | Baseline (Day -6 to Day 1) up to Week 12 |
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| Secondary | Change From Baseline to Week 12 in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment 8a Scale | PROMIS sleep-related impairment eight-term 8a scale was administered to assess impact of sleep-related impairment during waking hours. The questionnaire focuses on self-reported perceptions of alertness, sleepiness, and tiredness during usual waking hours, and perceived functional impairments during wakefulness associated with sleep problems or impaired alertness. It assesses sleep-related impairment over the past 7 days. Each item is rated on a 5-point scale (1 = not at all; 2 = a little bit; 3 = somewhat; 4 = quite a bit; and 5 = very much) with a raw score from 8 to 40 with higher scores indicating greater sleep impairment. PROMIS T-score is presented which rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. Possible range for T-score=30 to 80; higher scores=greater severity of sleep impairment. Baseline=last available valid (non-missing) value up to and including the day of first dose of investigational medicinal product (IMP). | The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported. | Posted | Least Squares Mean | Standard Error | T-score | Baseline (Day 1) up to Week 12 |
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| Secondary | Change From Baseline to Week 12 in Sleep Quality (Sleep Diary) | Sleep diary is used to assess adult sleep disturbance due to asthma. Sleep quality was assessed on a 11-point scale which ranged from 0 (worst possible sleep) to 10 (best possible sleep); higher scores indicated better outcomes. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1. | The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline (Day -6 to Day 1) up to Week 12 |
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| Secondary | Change From Baseline to Week 12 in Restorative Sleep (Sleep Diary) | Sleep Diary is used to assess adult sleep disturbance due to asthma. Question about restorative sleep asks participants to recall "when they got up for the day today". Restorative sleep was assessed on a 11-point scale which ranged from 0 (worst possible sleep) to 10 (best possible sleep); higher scores indicated better outcomes. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1. | The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline (Day -6 to Day 1) up to Week 12 |
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| Secondary | Change From Baseline to Week 12 in Wake After Sleep Onset (WASO) (Sleep Diary) | Sleep Diary is used to assess adult sleep disturbance due to asthma. WASO was calculated as time awake after initial sleep onset but before the final awakening. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1. | The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported. | Posted | Least Squares Mean | Standard Error | Minutes | Baseline (Day -6 to Day 1) up to Week 12 |
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| Secondary | Change From Baseline to Week 12 in WASO Based on Actigraphy Data | Wrist actigraphy is a procedure that records and integrates occurrence and degree of limb movement activity over an extended recording period. The signals generated by wrist movement are sensed by a tiny microcomputer contained within watch and translated into activity counts. Algorithms have been developed to translate these activity counts or "epochs" (or "periods") that correspond to times when a person is likely to be asleep or wake. Actigraph was worn on wrist of non-dominant hand to provide estimates of duration, timing and patterns of sleep in study participants. After the watch data were scored by a selected expert center, a number of summary measurements were generated for each participant, including WASO. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1. | The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported. | Posted | Least Squares Mean | Standard Error | Minutes | Baseline (Day -6 to Day 1) up to Week 12 |
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| Secondary | Change From Baseline to Week 12 in Asthma Daytime Symptom Diary (ADSD) | The ADSD is a PRO measure designed to measure asthma symptoms in adult and adolescent (12 years of age and older) participants diagnosed with mild to severe asthma. ADSD assesses asthma severity based on participant self-report of asthma core symptoms, i.e., difficulty breathing, wheezing, shortness of breath, chest tightness, chest pain, and cough. Participants were asked to complete the ADSD every night before they go to bed, thinking about their asthma symptoms today, from when they got up this morning until now. ADSD is composed of 6 items rated using an 11-point NRS that ranges from 0 = None to 10 = as bad as you can imagine. The total score was calculated by averaging all 6 items and therefore the score ranged from 0 to 10. Higher scores indicated worse outcomes. Baseline value was average of the data from Day -7 to Day -1. | The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline (Day -7 to Day -1) up to Week 12 |
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| Secondary | Change From Baseline to Week 12 in Asthma Nighttime Symptom Diary (ANSD) | The ANSD is a PRO measure designed to measure asthma symptoms in adult and adolescent (12 years of age and older) participants diagnosed with mild to severe asthma. ANSD assesses asthma severity based on participant self-report of asthma core symptoms, i.e., difficulty breathing, wheezing, shortness of breath, chest tightness, chest pain, and cough. Participants were asked to complete the ANSD when getting up, thinking about their asthma symptoms last night from when they went to bed until now. ANSD is composed of 6 items rated using an 11-point NRS that ranges from 0 = None to 10 = as bad as you can imagine. The total score was calculated by averaging all 6 items and therefore the score ranged from 0 to 10. Higher scores indicated worse outcomes. Baseline value was average of the data from Day -6 to Day -1. | The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline (Day -6 to Day -1) up to Week 12 |
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| Secondary | Change From Baseline to Week 12 in Pre-Bronchodilator Forced Expiratory Volume (Pre-BD FEV1) | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. For pre-BD FEV1, spirometry was performed before IMP administration and after withholding the standard of care asthma treatment which was verified before performing the measurements. Baseline was defined as the last available valid (non-missing) value up to and including the day of first dose of IMP. | The ITT analysis set consisted of all randomized participants included in the MMRM model. Only those participants with data collected at baseline and at least one post-baseline until Week 12 are reported. | Posted | Least Squares Mean | Standard Error | Liter | Baseline (Day 1) up to Week 12 |
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| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events Of Special Interest (TEAESIs) | AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs: AEs that developed or worsened or became serious during TEAE period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 98 days or until participant switches to commercialized dupilumab or other biologics. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. AESI: AE (serious or nonserious) of scientific and medical concern specific to Sponsor's product or program, for which ongoing monitoring and immediate notification by Investigator to Sponsor is required. | Safety analysis set included all randomized participants who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | From first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks |
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| Secondary | Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs | Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and weight. Criteria for PCSA: SBP: ≤95 millimeters of mercury (mmHg) and decrease from baseline ≥20 mmHg, ≥160 mmHg and increase from baseline ≥20 mmHg; DBP: ≤45 mmHg and decrease from baseline ≥10 mmHg, ≥ 110 mmHg and increase from baseline ≥ 10 mmHg; HR: ≤ 50 beats per minute (bpm) and decrease from baseline ≥ 20 bpm, ≥120 bpm and increase from baseline ≥ 20 bpm; Weight: ≥ 5% increase from baseline, ≥5% decrease from baseline. | Safety analysis set included all randomized participants who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | From first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks |
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TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months.
Analysis was performed on safety population.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dupilumab 200 mg Q2W | 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. | 0 | 100 | 3 | 100 | 13 | 100 |
| EG001 | 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. | 0 | 101 | 3 | 101 | 18 | 101 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pancreatitis Acute | Gastrointestinal disorders | MedDra 26.1 | Systematic Assessment |
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| Covid-19 Pneumonia | Infections and infestations | MedDra 26.1 | Systematic Assessment |
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| Urosepsis | Infections and infestations | MedDra 26.1 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDra 26.1 | Systematic Assessment |
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| Tibia Fracture | Injury, poisoning and procedural complications | MedDra 26.1 | Systematic Assessment |
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| Depression Suicidal | Psychiatric disorders | MedDra 26.1 | Systematic Assessment |
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| Suicide Attempt | Psychiatric disorders | MedDra 26.1 | Systematic Assessment |
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| Nephrolithiasis | Renal and urinary disorders | MedDra 26.1 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDra 26.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDra 26.1 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDra 26.1 | Systematic Assessment |
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The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | Sanofi aventis recherche & développement | 800-633-1610 ext 6# | Contact-US@sanofi.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 9, 2023 | Sep 30, 2024 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C582203 | dupilumab |
Not provided
Not provided
Not provided
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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. |
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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. |
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