E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 14.1 |
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 |
|
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 different doses and regimens of dupilumab in patients with moderate to severe, uncontrolled asthma |
Valutare l'efficacia a dosi e di regimi diversi di dupilumab in pazienti affetti da asma non controllata, da moderata a grave |
|
E.2.2 | Secondary objectives of the trial |
To evaluate different doses and regimens of dupilumab in patients with moderate to severe uncontrolled asthma, with regard to:
- Safety and tolerability
- Dupilumab systemic exposure and anti-drug antibodies
|
Valutare le dosi e i regimi diversi di dupilumab in pazienti affetti da asma non controllata da moderata a grave, con riferimento a:
• Sicurezza e tollerabilità
• Esposizione sistemica a dupilumab e anticorpi anti-farmaco |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with a physician diagnosis of moderate to severe, uncontrolled asthma for ≥12 months, based on the Global Initiative for Asthma (GINA) 2009 Guidelines and:
- Existing treatment with moderate- or high-dose inhaled corticosteroid / long-acting beta-2 agonist
- Forced expiratory volume (FEV1) 40 to 80% of predicted normal
- Juniper Asthma Control Questionnaire, 5-question version (ACQ-5) score ≥1.5
- Reversibility of at least 12% and 200 mL in forced expiratory volume (FEV1)
- Has experienced, within prior year: hospitalization, emergency or urgent care visit or systemic corticosteroid treatment for worsening asthma
|
• Pazienti con una diagnosi clinica di asma non controllata, da moderata a severa per un periodo ≥12 mesi, in base alle linee giuda ‘Global Initiative for Asthma Giudelines (GINA) 2009’ e ai seguenti criteri:
Trattamento in corso con dosi moderate o elevate di ICS/LABA [≥250 μg di fluticasone propionato;
Volume Espiratorio Massimo ad 1 Secondo (FEV1) tra il 40% e l'80% del valore normale previsto;
Punteggio ≥1,5 al questionario ACQ-5 (Questionario di controllo dell'asma Juniper, versione a 5 domande)
Reversibilità pari ad almeno il 12% e 200 ml di FEV1
Abbia riportato, nell'arco dell’anno precedente alla Visita 1: Ricovero in ospedale o visita medica urgente/d'emergenza,o trattamento con steroidi sistemici a causa di un peggioramento dell'asma
|
|
E.4 | Principal exclusion criteria |
- Patients <18 years
- Chronic obstructive pulmonary disease (COPD) or other lung diseases (eg, emphysema, idiopathic pulmonary fibrosis, Churg Strauss syndrome, allergic bronchopulmonary aspergillosis) which impair pulmonary function tests
- Chest X-ray within 12 months of screening visit or at screening visit with clinically significant findings of lung disease(s) other than asthma
- Current smoker or cessation of smoking within 6 months prior to Visit 1
- Previous smoker with a smoking history >10 pack-years
|
• Pazienti di età < 18 anni
• Broncopneumopatia cronica ostruttiva (COPD) o altre patologie polmonari (ad es., enfisema, fibrosi polmonare idiopatica, sindrome di Churg Strauss, aspergillosi broncopolmonare allergica) che pregiudichino i test di funzionalità polmonare
• Radiografia del torace, con evidenze clinicamente significative di patologie polmonari diverse dall'asma, nei 12 mesi precedenti la visita di screening o durante la visita di screening
• Paziente Fumatore o che abbia interrotto il fumo nei 6 mesi precedenti la Visita
• Ex fumatore con anamnesi positiva per fumo di più di 10 pacchetti all'anno |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in forced expiratory volume (FEV1) |
Variazione del FEV1 dal basale alla Settimana 12 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1) Relative change from baseline in FEV1
2) Annualized rate of loss of asthma control
3) Time to loss of asthma control
4) Change from baseline in asthma symptom scores |
• Variazione relativa (%) del FEV1 dal basale alla Settimana 12
• Tasso annualizzato di eventi di mancanza del controllo dell'asma
• Tempo intercorso tra gli eventi di mancanza di controllo dell'asma
• Variazione nel punteggio dei sintomi dell’asma rispetto al basale
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/4) Week 12
2/3) Week 24 |
Per gli endpoint 1 e 4: Settimana 12
Per gli endpoint 2 e 3: settimana 24
|
|
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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 5 |
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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Chile |
Japan |
Korea, Republic of |
Mexico |
New Zealand |
Russian Federation |
South Africa |
Turkey |
Ukraine |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 23 |