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 children 6 to <12 years of age with uncontrolled persistent asthma. |
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E.2.2 | Secondary objectives of the trial |
-To evaluate in children 6 to <12 years of age with uncontrolled persistent asthma:
-The safety and tolerability of dupilumab.
-The effect of dupilumab in improving patient-reported outcomes (PROs).
-The dupilumab systemic exposure and incidence of anti-drug antibodies.
-To explore the association between dupilumab treatment and pediatric immune responses to vaccines: any vaccination for tetanus, diphtheria, pertussis and/or seasonal trivalent/quadrivalent influenza vaccine. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Children 6 to <12 years of age, with a physician diagnosis of persistent asthma for ≥12 months prior to Screening, based on clinical history and examination, pulmonary function parameters according to Global initiative for asthma (GINA) 2015 Guidelines and the following criteria:
-Existing background therapy of medium-dose inhaled corticosteroids (ICS) with second controller medication (ie, long-acting β2 agonist [LABA], leukotriene receptor antagonist [LTRA], long acting muscarinic antagonist [LAMA], or methylxanthines) or high-dose ICS alone or high dose ICS with second controller, for at least 3 months with a stable dose ≥1 month prior to Screening Visit 1.
-Pre-bronchodilator forced expiratory volume in 1 second (FEV1) ≤95% of predicted normal or pre bronchodilator FEV1/forced vital capacity (FVC) ratio <0.85 at Screening and Baseline Visits.
-Reversibility of at least 10% in FEV1 after the administration of albuterol/salbutamol or levalbuterol/levosalbutamol reliever medication before randomization. Documented reversibility or positive airway hyperresponsiveness to methacholine within 12 months prior to Screening V1 is considered acceptable.
-Must have experienced within 1 year prior to Screening Visit 1 a Severe Exacerbation Event.
- Evidence of uncontrolled asthma, with at least one of the following criteria during the 4 (±1) weeks Screening Period:
-Asthma Control Questionnaire–Interviewer Administered (ACQ-IA) ACQ-5 score ≥1.5 on at least one day of the Screening Period.
-Use of reliever medication (ie, albuterol/salbutamol or levalbuterol/levosalbutamol), other than as a preventive for exercise induced bronchospasm, on 3 or more days per week, in at least one week during the Screening Period.
-Sleep awakening due to asthma symptoms requiring use of reliever medication at least once during the Screening Period.
-Asthma symptoms 3 or more days per week in at least one week during the Screening Period. |
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E.4 | Principal exclusion criteria |
-Patients <6 or ≥12 years of age.
-Patients with <16 kg bodyweight.
-Any other chronic lung disease (cystic fibrosis, bronchopulmonary dysplasia, etc) which may impair lung function.
-A subject with any history of life threatening asthma (ie, extreme exacerbation that requires intubation).
-Co-morbid 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) |
Annualized rate of severe exacerbation events during treatment period |
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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 from baseline in pre-bronchodilator % predicted forced
expiratory volume in 1 second (FEV1)
2) Change from baseline in pre-bronchodilator % predicted
FEV1
3) Time to first severe exacerbation event
4) Time to first loss of asthma control event
5) Change from baseline in other lung function measurements
6) Change from baseline in morning asthma symptom score
7) Change from baseline in evening asthma symptom score
8) Number of nocturnal awakenings due to asthma symptoms
requiring the use of reliever medication
9) Number of rescue medication inhalations
10) Assessment of Patient Reported Outcomes: Asthma Control Questionnaire
11) Assessment of Patient Reported Outcomes: Pediatric Asthma quality of life questionnaire
12) Assessment of IgG responses to vaccination during dupilumab
treatment (may be analyzed as exploratory endpoint if insufficient power) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Baseline, Week 12
2) Baseline, Weeks 2, 4, 8, 24, 36, 52
3) to 4): Up to 52 weeks
5) to 10): Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
11) Baseline, Weeks 12, 24, 36, 52
12) 2 blood draws per vaccine scheduled:1
prevaccination and 1 post-vaccination |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Chile |
Colombia |
Mexico |
South Africa |
United States |
Lithuania |
Poland |
Romania |
Spain |
Italy |
Hungary |
Turkey |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |