E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of dupilumab on sleep |
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E.2.2 | Secondary objectives of the trial |
-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 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
To evaluate the effect of dupilumab on additional objective sleep assessments using polysomnography (PSG)-tertiary/exploratory objective |
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E.3 | Principal 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 asthma exacerbation within 1 year prior to screening. 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 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, 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 |
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E.4 | Principal exclusion criteria |
- Current smoker - Former smoker for 10 years with a smoking history of >10 pack-years - 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 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 - Treatment with live (attenuated) vaccine within 4 weeks before screening Visit 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1 - 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 2 - 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. 3 - Change in sleep quality in Sleep Diary ; Change from baseline to Week 12 in sleep quality (Sleep Diary) 4 - Change in restorative sleep in Sleep Diary ; Change from baseline to Week 12 in restorative sleep (Sleep Diary) 5 - Change in WASO in Sleep Diary ; Change from baseline to Week 12 in wake after sleep onset (WASO) (Sleep Diary) 6 - Change in WASO (actigraphy data) ; Change from baseline to Week 12 in WASO based on actigraphy data 7 - 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) 8 - Change in pre-BD FEV1 ; Change from baseline to Week 12 in prebronchodilator forced expiratory volume in 1 second (pre-BD FEV1) 9 - 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 2, 3, 4, 5, 6, 7, 8 : Baseline to Week 12 9 : Baseline to Week 24 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Russian Federation |
Ukraine |
United States |
Germany |
Italy |
Netherlands |
Portugal |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 10 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 17 |