E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe atopic dermatitis (AD). |
Dermatitis atópica de grado moderado a severo. |
|
E.1.1.1 | Medical condition in easily understood language |
Moderate to severe atopic dermatitis (AD). |
Dermatitis atópica de grado moderado a severo. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
E.1.2 | System Organ Class | 100000004858 |
|
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 |
Assess the efficacy of dupilumab over 12 weeks of treatment in adult
patients with moderate-to-severe atopic dermatitis (AD) who have failed or are intolerant to topical steroids with or without topical calcineurin inhibitors. |
Evaluar la eficacia de dupilumab durante 12 semanas de tratamiento en pacientes adultos con dermatitis atópica (DA) de grado moderado a severo en los que han fracasado los corticoides tópicos, con o sin inhibidores de la calcineurina tópicos. |
|
E.2.2 | Secondary objectives of the trial |
-Evaluate efficacy over time of dupilumab when administered for up to 52 weeks.
-Evaluate the long-term safety of dupilumab administered for up to 52 weeks. |
- Evaluar la eficacia de dupilumab a lo largo del tiempo en su administración durante un máximo de 52 semanas.
- Evaluar la seguridad a largo plazo de dupilumab en su administración durante un máximo de 52 semanas. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optional Genomics Sub-study.
- Blood for DNA extraction should be collected on day 1/baseline (predose), but may be collected at any study visit.
- The purpose of the genomic analyses is to identify genomic associations with clinical or biomarker response to IL-4R/13R modulation, atopic disease risk, prognosis and progression, or other clinical outcome measures. |
Subestudio genómico opcional:
- Muestra de ADN debería obtenerse el Día 1/basal; no obstante, podrá extraerse en cualquier momento a lo largo del estudio.
-El objetivo de los análisis genómicos es identificar asociaciones genómicas con las respuestas clínicas o de biomarcadores a la modulación de IL-4R/13R, con el riesgo de desarrollar enfermedades atópicas, con el pronóstico y la progresión de la enfermedad, o con otras medidas de resultados clínicos. |
|
E.3 | Principal inclusion criteria |
1. Male or female, 18 years or older
2. Chronic AD, (according to the American Academy of Dermatology Consensus Criteria),that has been present for at least 3 years before the screening visit.
3. Patients with documented recent history (within 6 months before the
screening visit) of inadequate response to a sufficient course of
outpatient treatment with topical AD medication(s), or for whom topical AD therapies are medically inadvisable. |
1. Varón o mujer de 18 o más años de edad.
2. DA crónica (de acuerdo con los Criterios de consenso de la Sociedad Estadounidense de Dermatología (American Academy of Dermatology Consensus Criteria) que haya estado presente durante como mínimo los 3 años anteriores a la visita de selección.
3. Pacientes con antecedentes recientes (dentro de los 6 meses previos a la visita de selección) documentados de respuesta inadecuada a un tratamiento suficiente con uno o varios medicamentos tópicos para la DA o para los cuales las terapia de DA tópica es medicamente desaconsejable. |
|
E.4 | Principal exclusion criteria |
1. Prior treatment with dupilumab
2. Recent treatment (within specific time windows before the baseline
visit) with systemic corticosteroids, immunosuppressive agents, topical
corticosteroids and calcineurin inhibitors, live (attenuated) vaccine,
other investigational drugs
3. History of human immunodeficiency virus (HIV) infection
4. HIV or viral hepatitis seropositivity at screening
5. Known or suspected immunosuppresion
6. Recent infections requiring antiinfectious treatment
7. Recent history or high risk of clinical endoparasitoses
8. High risk populations (low life expectancy, severe concomitant
diseases, etc.)
9. Pregnant or breast-feeding women
10. Patients of reproductive potential and sexually active who are
unwilling to use adequate contracepcion. |
1. Participación previa en un ensayo clínico con dupilumab.
2. Tratamiento reciente con corticoides sistemicos, agentes inmunosupresores, corticosteroides tópicos e inhibidores de la calceneurina, vacunas vivas (atenuadas), otros fármacos en investigación.
3. Historia de infección por el virus del VIH.
4. Hepatitis viral o VIH seropositivo en el screening.
5. Sopecha o Inmunosupresión conocida.
6. Infecciones recientes que requiren tratamiento antiinfeccioso.
7. Historia reciente o alto riesgo de endoparasitosis clínica.
8. Poblaciones de alto riesgo (esperanza de vida baja, enfermedades concomitantes graves, etc...).
9. Mujeres embarazadas o en periodo de lactancia.
10. Pacientes con potencial reproductivo y sexualmente activos los cuales no desean usar métodos anticonceptivos adecuados |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Percentage of patients with EASI-50 response (reduction of EASI score by at least 50% from baseline) at week 12.
- Percentage of patients with IGA 0 or 1 at week 12 |
- Porcentaje de pacientes que alcanzan una respuesta EASI 50 (reducción de un 50%, como mínimo, de la puntuación EASI respecto a la situación basal) en la semana 12.
- Porcentaje de pacientes con una VGI de 0 o 1 en la semana 12 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- The change from baseline in maximum itch intensity (NRS) at week 12
- The change from baseline in BSA at week 12
- The change from baseline in the erythema of GISS at week 12
- The change from baseline in the infiltration/papulation of GISS at week 12
- The change from baseline in the excoriations of GISS at week 12
- The change from baseline in the lichenification of GISS at week 12
- Percentage of patients achieving EASI-50 response (reduction of EASI
score by at least 50% from baseline) at week 12 and maintaining EASI-50 response on at least 6 of the10 subsequent every 4 weeks (q4w) visits (from visits at weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, and week 52); 1 of the 6 must be in the last 4 visits (weeks 40, 44,
48 and 52).
- Percentage of patients with IGA 0 to 1 at week 12 and maintaining IGA 0 to 2 on at least 6 of the10 subsequent q4w visits (from visits at weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, and week 52); 1 of the 6 must be in the last 4 visits (weeks 40, 44, 48 and 52).
- The change from baseline in oozing/crusting at week 12
- Incidence of serious treatment-emergent adverse events (TEAEs)
through week 56
- Incidence of study drug discontinuation due to an AE through week 56.
- Incidence of skin-infections through week 56 |
- Cambio en la intensidad máxima del prurito (ENV) en la semana 12 respecto a la situación basal.
- Cambio en la SCDA en la semana 12 respecto a la situación basal.
- Cambio en el eritema de la puntuación GISS en la semana 12 respecto a la situación basal
- Cambio en la infiltración/presencia de pápulas de la puntuación GISS en la semana 12 respecto a la situación basal
-Cambio en las excoriaciones de la puntuación GISS en la semana 12 respecto a la situación basal
-Cambio en la liquenificación de la puntuación GISS en la semana 12 respecto a la situación basal.
- Porcentaje de pacientes que alcanzan una respuesta EASI 50 (reducción de la puntuación EASI en un 50% como mínimo respecto a la situación basal) en la semana 12 y que posteriormente mantienen la respuesta EASI 50 en 6 de las 10 visitas subsiguientes (efectuadas cada 4 semanas: visitas de las semanas 16, 20, 24, 28, 32, 36, 40, 44, 48 y 52) como mínimo; una de las seis visitas deberá ser obligatoriamente una de las cuatro últimas (semanas 40, 44, 48 y 52).
-Porcentaje de pacientes con una VGI de 0 ó 1 en la semana 12 y que posteriormente mantienen una VGI de 0 a 2 en 6 de las 10 visitas subsiguientes (efectuadas cada 4 semanas: visitas de las semanas 16, 20, 24, 28, 32, 36, 40, 44, 48 y 52) como mínimo; una de las seis visitas deberá ser obligatoriamente una de las cuatro últimas (semanas 40, 44, 48 y 52).
-Cambio en los exudados/costras en la semana 12 respecto a la situación basal.
-Incidencia de acontecimientos adversos graves observados durante el tratamiento (AAOT) hasta la semana 56
-Incidencia de suspensiones del fármaco del estudio debido a AA hasta la semana 56
-Incidencia de infecciones cutáneas hasta la semana 56 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Week 12
2) Week 12.
3) Week 12.
4) Week 12.
5) Week 12.
6) Week 12.
7) Week 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and week 52.
8) Week 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and week 52.
9) Week 12.
10) Week 56
11) Week 56
12) Week 56
10) Week 56
11) Week 56
12) Week 56. |
1) Semana 12.
2) Semana 12.
3) Semana 12.
4) Semana 12.
5) Semana 12.
6) Semana 12.
7) Semana 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, y semana 52.
8) Semana 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, y semana 52.
9) Semana 12.
10) Semana 56.
11) Semana 56.
12) Semana 56. |
|
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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | 3 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 105 |
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 |
Australia |
Belgium |
Bulgaria |
Canada |
Croatia |
Czech Republic |
Denmark |
France |
Germany |
Greece |
Hungary |
Italy |
Korea, Republic of |
Latvia |
Netherlands |
New Zealand |
Poland |
Romania |
Russian Federation |
Spain |
Taiwan |
United Kingdom |
|
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
|
Last Patient Last Visit |
Último Paciente Última Visita |
|
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 | 0 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |