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 | 18.0 |
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. |
Evaluar la eficacia de dupilumab (SAR231893 [REGN668]) en pacientes con asma persistente |
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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. |
Evaluar la seguridad y la tolerabilidad de dupilumab Evaluar el efecto de dupilumab en la mejoría de los resultados notificados por el paciente (Patient- Reported Outcomes, PROs) incluyendo la calidad de vida relacionada con la salud (HRQoL) Evaluar la exposición sistémica a dupilumab y la incidencia de anticuerpos antifármaco (AAF) |
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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, leukotrine 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. |
Pacientes adultos y adolescentes con un diagnóstico médico de asma de ? 12 meses, basado en las Directrices de la Iniciativa Global para el Asma (Global Initiative for Asthma, GINA) de 2014 y los siguientes criterios: A) Tratamiento existente con una dosis de media a alta de ICS (? 250 mcg de propionato de fluticasona dos veces al día o una dosis diaria de un ICS equivalente, hasta un máximo de 2000 mcg/día, de propionato de fluticasona o equivalente) en combinación con un segundo medicamento de control (p. ej., LABA, LTRA) durante, al menos, 3 meses con una dosis estable ? 1 mes antes de la Visita 1. - Nota para Japón: En el caso de pacientes de 18 años o más, la dosis de ICS debe ser de ? 200 mcg de propionato de fluticasona dos veces al día o equivalente; en el caso de pacientes de 12 a 17 años, la dosis de ICS debe ser de ? 100 mcg de propionato de fluticasona dos veces al día o equivalente. - Los pacientes que necesiten un tercer medicamento de control para su asma se considerarán aptos para este estudio y, también, se deberá utilizar durante al menos 3 meses con una dosis estable ? 1 mes antes de la Visita 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). Clinical evidence or imaging (eg, chest X-ray, computed tomography) within 12 months of Visit 1 consistent with 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. Comorbid disease that might interfere with the evaluation of Investigational Medicinal Product. |
? Pacientes < 12 años de edad o la edad legal mínima para adolescentes en el país del centro de investigación, la que sea mayor (en aquellos países en los que las regulaciones locales permitan únicamente la inclusión de adultos, el reclutamiento de pacientes se limitará a aquellos que tengan ? 18 años). ? Peso inferior a 30 kilogramos. ? Enfermedad pulmonar obstructiva crónica (EPOC) u otras enfermedades pulmonares (p. ej., fibrosis pulmonar idiopática, síndrome de Churg-Strauss, etc.) que puedan afectar a la función pulmonar. ? Un paciente que experimente una exacerbación de asma grave (definida como un empeoramiento del asma que dé lugar a un tratamiento de emergencia, hospitalización por asma o tratamiento con esteroides sistémicos en cualquier momento, desde el mes previo a la Visita de Selección hasta la visita basal inclusive). ? Evidencias clínicas o diagnóstico por imagen (p. ej., radiografía de tórax, tomografía computarizada [TAC], resonancia magnética [RM]) en los 12 meses previos a la Visita 1 coherente con enfermedad(es) pulmonar(es) que no sea(n) asma. ? Fumador actual o cese del hábito de fumar en los 6 meses previos a la Visita 1. ? Fumador previo con un antecedente de tabaquismo > 10 paquetes/año. ? Enfermedad comórbida que pudiera interferir con la evaluación del PI. |
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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) |
a) Tasa anualizada de episodios de exacerbación grave b) Cambio absoluto desde el momento basal en VEF1 prebroncodilatador Variable |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
a) 52 weeks b) Week 12 |
a) durante el periodo de tratamiento controlado con placebo de 52 semanas b) a la Semana 12 |
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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 |
a) Cambio porcentual desde la basal en VEF1 prebroncodilatador b) Cambio absoluto desde la basal en VEF1 prebroncodilatador c) Cambio porcentual desde la basal en VEF1 prebroncodilatador desde el d) Tasa anualizada de episodios de pérdida de control del asma (loss of asthma control, LOAC) e) Tasa anualizada de episodios de exacerbación grave que precisaron hospitalización o visita a urgencias f) Tiempo hasta el primer episodio de exacerbación grave g) Tiempo hasta el primer episodio de pérdida de control del asma (LOAC) |
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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 |
a) Semana 12 b) Semana 2,4,8,24,36 y 52 c) Semana 2,4,8,24,36 y 52 d) Semana 52 e) Semana 52 f) Semana 52 g) Semana 52 |
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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 | 10 |
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 |
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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LVLS |
Última visita del último paciente |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 25 |
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 |