E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Eosinophilic Esophagitis (EoE) |
Esofagitis eosinofílica (EEo) |
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E.1.1.1 | Medical condition in easily understood language |
A chronic allergic/immune condition characterized by inflammation of the esophagus |
Enfermedad crónica alérgica/inmune caracterizada por la inflamación del esófago |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064212 |
E.1.2 | Term | Eosinophilic oesophagitis |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal 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 |
The primary objectives of the study by study part are: Part A: To determine the treatment effect of dupilumab compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures, and to inform/confirm the final sample size determination for Part B. Part B: To demonstrate the efficacy of dupilumab treatment compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures. Part C: To assess the safety and efficacy of dupilumab treatment in adult and adolescent patients with EoE after up to 52 weeks of treatment as assessed by histological and clinical measures. |
Los objetivos principales para cada parte del estudio son: Parte A Determinar el efecto del tratamiento con dupilumab en comparación con placebo en pacientes adultos y adolescentes con EEo tras 24 semanas de tratamiento, evaluado mediante medidas histológicas y clínicas, y notificar/confirmar la determinación del tamaño muestral final para la Parte B. Parte B Demostrar la eficacia del tratamiento con dupilumab en comparación con placebo en pacientes adultos y adolescentes con EEo tras 24 semanas de tratamiento, evaluado mediante medidas histológicas y clínicas. Parte C Evaluar la seguridad y la eficacia del tratamiento con dupilumab en pacientes adultos y adolescentes con EEo tras un máximo de 52 semanas de tratamiento, según la evaluación de las medidas histológicas y clínicas. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: -To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up to 52 weeks in adult and adolescent patients with EoE -To explore the relationship between dupilumab concentration and responses in adult and adolescent patients with EoE, using descriptive analyses |
Los objetivos secundarios del ensayo son: •Evaluar la seguridad, tolerabilidad e inmunogenicidad del tratamiento con dupilumab durante un máximo de 52 semanas en pacientes adultos y adolescentes con EEo •Explorar la relación entre la concentración de dupilumab y las respuestas en pacientes adultos y adolescentes con EEo, utilizando análisis descriptivos |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. A documented diagnosis of EoE by endoscopic biopsy prior to screening 2. Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration 3. History (by patient report) of an average of at least 2 episodes of dysphagia (with intake of solids) per week in the 4 weeks prior to screening. |
1. Un diagnóstico documentado de EEo mediante biopsia endoscópica antes de la selección 2. Las biopsias endoscópicas iniciales con una demostración en la lectura central de infiltración eosinofílica intraepitelial 3. Antecedente (notificado por el paciente) de una media de 2 episodios de disfagia (con ingesta de sólidos) a la semana en las 4 semanas previas a la selección |
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria (Parts A & B): 1. Body weight ≤40 kg 2. Prior participation in a dupilumab clinical trial, or past or current treatment with dupilumab 3. Initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food group in the 6 weeks prior to screening. 4. Other causes of esophageal eosinophilia or the following conditions: hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) 5. Active Helicobacter pylori infection 6. History of achalasia, Crohn’s disease, ulcerative colitis, celiac disease, and prior esophageal surgery 7. Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to10 mm upper endoscope or any critical esophageal stricture that requires dilation at screening 8. History of bleeding disorders or esophageal varices 9. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study
Key Exclusion Criteria (Part C): 1. Participants who, during the double-blind treatment period (Part A or Part B), developed a serious adverse event (SAE) and/or adverse event (AE) deemed related to study drug, which in the opinion of the investigator could indicate that continued treatment with study drug may present an unreasonable risk for the participant. 2. Participants who became pregnant during the double-blind treatment period 3. Participants who are prematurely discontinued from study drug due to an AE (patients who are prematurely discontinued from study drug due to lack of efficacy are eligible to enter Part C) 4. Patients who did not undergo endoscopy with biopsies prior to receiving rescue treatment |
Criterios de exclusión clave (Partes A y B): 1. Peso corporal ≤40 kg 2. Participación previa en un ensayo clínico de dupilumab, o tratamiento pasado o actual con dupilumab 3. Inicio o cambio de un régimen dietario con eliminación de alimentos o reintroducción de un grupo alimentario eliminado previamente en las 6 semanas previas a la selección. 4. Otras causas de eosinofilia de esófago o las siguientes afecciones: síndrome hipereosinofílico y granulomatosis eosinofílica con poliangitis (síndrome de Churg-Strauss) 5. Infección activa por Helicobacter pylori 6. Antecedentes de acalasia, enfermedad de Crohn, colitis ulcerosa, enfermedad celíaca y cirugía de esófago previa 7. Cualquier estenosis esofágica que no se pueda superar mediante endoscopia superior diagnóstica, estándar, de 9 a 10 mm o cualquier estenosis esofágica que requiera dilatación en la selección 8. Antecedentes de trastornos hemorrágicos o varices esofágicas 9. Mujeres embarazadas o en periodo de lactancia, o mujeres que pretendan quedarse embarazadas o amamantar durante el estudio. Criterios de exclusión clave (parte C): 1. Participantes que, durante el periodo de tratamiento doble ciego (parte A o parte B), desarrollaron un acontecimiento adverso grave (AAG) y/o un acontecimiento adverso (AA) que se considera relacionado con el fármaco del estudio, lo que en opinión del investigador podría indicar que la continuación del tratamiento con el fármaco del estudio podría representar un riesgo no justificado para el participante. 2. Participantes que hayan quedado embarazadas durante el periodo de tratamiento doble ciego. 3. Participantes que hayan interrumpido prematuramente el fármaco del estudio debido a un AA (los pacientes que hayan interrumpido prematuramente el fármaco del estudio debido a la falta de eficacia son aptos para incorporarse a la parte C). 4. Pacientes que no se sometieron a endoscopia con biopsia antes de recibir el tratamiento de rescate. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The co-primary endpoints for both Parts A and B of the study are: - Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf at week 24 - Absolute change in DSQ score from baseline to week 24 |
Los criterios de valoración coprincipales para la Parte A y para la Parte B son: •Proporción de pacientes que logran un recuento máximo de eosinófilos intraepiteliales en el esófago de ≤6 eos/hpf en la semana 24 •Cambio absoluto en la puntuación del DSQ desde el inicio hasta la semana 24 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At week 24. Note: All the above co-primary and secondary endpoints assessed at week 24 will be assessed at week 52 as secondary endpoints |
En la semana 24. Nota: Todos los criterios de valoración coprincipales y secundarios en la semana 24 se evaluarán en la semana 52 como criterios de valoración secundarios |
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E.5.2 | Secondary end point(s) |
The key secondary endpoints of the study are: -Absolute change in EoE endoscopic reference score (EREFS) from baseline to week 24 -Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) from baseline to week 24 -Absolute change in EoE Histology Scoring System (EoEHSS) from baseline to week 24
The other secondary endpoints are: -Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤15 eos/hpf at week 24 -Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf at week 24 -Percent change in DSQ from baseline to week 24 -Absolute change from baseline to week 24 in health-related QOL as measured by EoE Impact Questionnaire (EoE-IQ) -Absolute change from baseline to week 24 in severity and/or frequency of EoE symptoms other than dysphagia |
Los criterios de valoración secundarios clave para la Parte A y para la Parte B del estudio son: - Cambio absoluto en la puntuación de referencia endoscópica de esofagitis eosinofílica (Eosinophilic Esophagitis-Endoscopic Reference Score, EoE-EREFS) desde el inicio hasta la semana 24 - Porcentaje de cambio en el recuento máximo de eosinófilos intraepiteliales en el esófago (eos/hpf) desde el inicio hasta la semana 24 - Cambio absoluto en el sistema de puntuación en la histología de EEo (Absolute change in EoE Histology Scoring System, EoEHSS) desde el inicio hasta la semana 24 Otros criterios de valoración secundarios incluyen los siguientes: - Proporción de pacientes que logran un recuento máximo de eosinófilos intraepiteliales en el esófago de ≤15 eos/hpf en la semana 24 - Proporción de pacientes que logran un recuento máximo de eosinófilos intraepiteliales en el esófago de ≤1 eos/hpf en la semana 24 - Porcentaje de cambio en el DSQ desde el inicio hasta la semana 24 - Cambio absoluto desde el inicio hasta la semana 24 en la calidad de vida (CdV) relacionada con la salud medida por el cuestionario sobre el impacto de EEo (EoE Impact Questionnaire, EoE-IQ) - Cambio absoluto desde el inicio hasta la semana 24 en la intensidad y/o la frecuencia de los síntomas de EEo distintos de la disfagia |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At week 24. Note: All the above co-primary and secondary endpoints assessed at week 24 will be assessed at week 52 as secondary endpoints |
En la semana 24. Nota: Todos los criterios de valoración coprincipales y secundarios en la semana 24 se evaluarán en la semana 52 como criterios de valoración secundarios |
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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 | 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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Periodo de 24 semanas de tratamiento doble ciego seguido por una fase abierta de 28 semanas |
24-week double-blind treatment period followed by 28-week open-label treatment period |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 |
Canada |
Denmark |
France |
Germany |
Italy |
Netherlands |
Portugal |
Spain |
Sweden |
Switzerland |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |