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 evaluate the efficacy of dupilumab in patients with persistent asthma |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the safety and tolerability of dupilumab -To evaluate the effect of dupilumab on improving patient reported outcomes including health related quality of life -To evaluate dupilumab systemic exposure and immunogenicity
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Adults and adolescent patients (≥12 years of age) with a physician diagnosis of asthma for ≥12 months, based on the Global Initiative for Asthma 2017 Guidelines and the following criteria: -Patients requiring a third controller for their asthma will be considered eligible for this study, and it should also be used for at least 3 months with a stable dose ≥1 month prior to the screening visit (Visit 1). -Patients requiring maintenance oral corticosteroids (OCS) with a stable dose ≤10 mg/day prednisone or equivalent will be allowed; OCS should be used for at least 3 months with a stable dose ≥1 month prior to the screening visit (Visit 1). -Pre-bronchodilator FEV1 ≤ 80% of predicted normal for adults and ≤90% of predicted normal for adolescents at the screening visit and the randomization visit (Visits 1 and 2), prior to randomization. -Asthma Control Questionnaire 5-question version (ACQ-5) score ≥1.5 at the screening visit and the randomization visit (Visits 1 and 2), prior to randomization. - For patients not requiring maintenance OCS, screening blood eosinophil count ≥150 cells/μL or FENO ≥25 parts per billion (ppb); for patients requiring maintenance OCS, there is no minimum requirement for blood eosinophil count and FENO level
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E.4 | Principal exclusion criteria |
-Patients <12 years of age or the minimum legal age for adolescents in the country of the investigative site, whichever is higher (for those countries where local regulations permit enrollment of adults only, patient recruitment will be restricted to those who are ≥18 years of age). - Weight is less than 30 kg at the screening visit (Visit 1) or the randomization visit (Visit 2). - Chronic obstructive pulmonary disease or other lung diseases (eg, idiopathic pulmonary fibrosis) which may impair lung function. - A patient who experiences a severe asthma exacerbation (defined as deterioration of asthma that results in emergency treatment, hospitalization due to asthma, treatment with systemic steroids, or treatment with systemic steroid at least twice the previous dose for patients on OCS maintenance) at any time from 1 month prior to the screening visit (Visit 1) up to and including the randomization visit (Visit 2). - Evidence of lung disease(s) other than asthma, either clinical or imaging evidence (eg, chest X-ray, computed tomography, and magnetic resonance imaging) within 3 months prior to the screening visit (Visit 1) as per local standard of care. - Current smoker or cessation of smoking within 6 months prior to the screening visit (Visit 1). - Previous smoker with a smoking history >10 pack-years. - Comorbid disease that might interfere with the evaluation of investigational medicinal product (IMP)
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in pre-bronchodilator forced expiratory volume (FEV1) - Absolute change from baseline in pre-bronchodilator FEV1 at Week 12 |
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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) |
-Annualized rate of severe exacerbation events -Percent change from baseline in pre-bronchodilator FEV1 -Annualized rate of loss of asthma control (LOAC) event -Annualized rate of severe exacerbation events resulting in hospitalization or emergency room visit -Time to first severe exacerbation event -Time to first LOAC -Change from baseline in Asthma Control Questionnaire (ACQ)-5 score -Change from baseline in ACQ-7 score -Morning/evening asthma symptom score (e-diary) -Nocturnal awakenings (e-diary) -Use of daily puffs of rescue medication -Change from baseline in Asthma Quality of Life Questionnaire (AQLQ) with Standardized Activities (≥12 years) (AQLQ+12) -Change from baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) -Assessment of adverse events (AEs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.,3. - 6. during the 24-week placebo-controlled treatment period 2. Baseline to week 12 7. - 13. Baseline to week 24 14. Baseline to week 36
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13 | Others | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |