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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 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 |
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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
- 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. |
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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-bronchodilator (BD) FEV1 ; Change from baseline to Week 12 in prebronchodilator forced expiratory volume in 1 second (pre-BD FEV1)
9 -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 |
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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 | 7 |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 17 |