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 (SAR231893 [REGN668]) 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 in improving patient-reported outcomes including health related quality of life. To evaluate dupilumab systemic exposure and incidence of antidrug antibodies.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adults and adolescent patients with a physician diagnosis of asthma for ≥12 months, based on the Global Initiative for Asthma (GINA) 2014 Guidelines and the following criteria: - Existing treatment with medium to high dose ICS (≥250 mcg of fluticasone propionate twice daily or equipotent ICS daily dosage to a maximum of 2000 mcg/day of fluticasone propionate or equivalent) in combination with a second controller (eg, long-acting beta agonist, leukotriene receptor antagonist) for at least 3 months with a stable dose ≥1 month prior to Visit 1. - Note for Japan: for subjects aged 18 years and older, ICS must be on ≥200 mcg of fluticasone propionate twice daily or equivalent; for subjects aged 12 to 17 years, ICS must be ≥100 mcg of fluticasone propionate twice daily or equivalent). - 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 Visit 1.
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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, subject recruitment will be restricted to those who are ≥18 years of age). Weight is less than 30 kilograms. Chronic obstructive pulmonary disease or other lung diseases (eg, idiopathic pulmonary fibrosis, Churg-Strauss Syndrome, etc) which may impair lung function. A subject who experiences a severe asthma exacerbation (defined as a deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with systemic steroids at any time from 1 month prior to the Screening Visit up to and including the Baseline Visit). Evidence of lung disease(s) other than asthma, either clinical evidence or imaging (Chest X-ray, CT, MRI) within 12 months of Visit 1 or at the screening visit, as per local standard of care. Note for Japan: According to the request from the health authority, chest X-ray should be performed at screening visit if there is no chest imaging (Chest X-ray, CT, MRI) available within 3 months prior to screening to exclude patients with suspected active or untreated latent tuberculosis. Current smoker or cessation of smoking within 6 months prior to Visit 1. Previous smoker with a smoking history >10 pack-years. Comorbid disease that might interfere with the evaluation of Investigational Medicinal Product. |
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E.5 End points |
E.5.1 | Primary end point(s) |
a) Annualized rate of severe exacerbation events b) Absolute change from baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) |
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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) |
a) Percent change from baseline in pre-bronchodilator FEV1 b) Absolute change from baseline in pre-bronchodilator FEV1 c) Percent change from baseline in pre-bronchodilator FEV1 d) Annualized rate of loss of asthma control (LOAC) event e) Annualized rate of severe exacerbation events resulting in hospitalization or emergency room visit f) Time to first severe exacerbation event g) Time to first loss of asthma control event
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) Week 12 b) Weeks 2, 4, 8, 24, 36, and 52 c) Weeks 2, 4, 8, 24, 36, and 52 d) 52 weeks e) 52 weeks f) 52 weeks g) 52 weeks
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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 | 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 | 4 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 59 |
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 |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Mexico |
Poland |
Russian Federation |
South Africa |
Spain |
Taiwan |
Turkey |
Ukraine |
United Kingdom |
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.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 25 |