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) including health related quality of life (HRQoL). -The dupilumab systemic exposure and incidence of anti-drug antibodies. -To evaluate 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 200 to 400 mcg (2 to 4 puff inhalations with metered-dose inhaler [MDI]) of albuterol/salbutamol or 45 to 90 mcg (2 to 4 puffs with MDI) of levalbuterol/levosalbutamol reliever medication before randomization (up to 3 opportunities during the same visit are allowed with a maximum of 12 puffs of reliever medication if tolerated by the patient). -Must have experienced within 1 year prior to Screening Visit 1, any of the following events: -Treatment with a systemic corticosteroid (SCS, oral or parenteral), as prescribed by a healthcare professional for worsening asthma at least once or, -Hospitalization or emergency room visit for worsening asthma. - 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: absolute and relative FEV1 6) Change from baseline in other lung function measurements: AM/PM peak expiratory flow (PEF) 7) Change from baseline in other lung function measurements: Forced Vital Capacity 8) Change from baseline in other lung function measurements: Forced expiratory flow (FEF) 25-75% 9) Change from baseline in other lung function measurements: Post bronchodilator % predicted FEV1 10) The effect of dupilumab on healthcare resource utilization 11) Change from baseline in morning asthma symptom score 12) Change from baseline in evening asthma symptom score 13) Number of nocturnal awakenings due to asthma symptoms requiring the use of reliever medication 14) Number of rescue medication inhalations 15) Assessment of Patient Reported Outcomes: Asthma Control Questionnaire 16) Assessment of Patient Reported Outcomes: Pediatric Asthma quality of life questionnaire 17) Assessment of IgG responses to vaccination during dupilumab treatment (may be analyzed as exploratory endpoint if insufficient power) 18) Adverse Events 19) Anti-Drug Antibodies 20) Serum Dupilumab Concentrations |
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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 9) and 11) to 15): Baseline, Weeks 2, 4, 8, 12, 24, 36, 52 10) Baseline, Week 52 16) Baseline, Weeks 12, 24, 36, 52 17) 2 blood draws per vaccine scheduled: 1 prevaccination and 1 post-vaccination 18) Up to Week 64 19) Baseline, Weeks 12, 24, 52, 64 20) Baseline, Weeks 6, 12, 24, 52, 64 |
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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 |
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 | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Argentina |
Australia |
Brazil |
Canada |
Chile |
Colombia |
Hungary |
Italy |
Lithuania |
Mexico |
Poland |
Romania |
Russian Federation |
South Africa |
Spain |
Turkey |
Ukraine |
United States |
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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.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |