E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Eosinophilic esophagitis (EoE) is a rare, chronic inflammatory disorder triggered by an immune response to foods and aeroantigens and characterized by a combination of esophageal dysfunction and eosinophilic infiltration of the esophagus |
La esofagitis eosinofílica (EoE) es un trastorno inflamatorio crónico raro desencadenado por una respuesta inmunitaria a los alimentos y aeroantígenos y caracterizado por una combinación de disfunción esofágica e infiltración eosinofílica del esófago. |
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E.1.1.1 | Medical condition in easily understood language |
Eosinophilic esophagitis (EoE) Allergic Esophagitis |
Esofagitis eosinofílica (EoE) Esofagitis alérgica |
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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 | LLT |
E.1.2 | Classification code | 10064220 |
E.1.2 | Term | Eosinophilic esophagitis |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To evaluate the effect of tezepelumab on the histologic response in adult and adolescent participants with symptomatic and histologically active EoE 2. To evaluate the effect of tezepelumab on symptom improvement in adult and adolescent participants with symptomatic and histologically active EoE |
1. Evaluar el efecto de tezepelumab sobre la respuesta histológica en participantes adultos y adolescentes con EoE sintomática e histológicamente activa. 2. Evaluar el efecto de tezepelumab sobre la mejoría de los síntomas en participantes adultos y adolescentes con EoE sintomática e histológicamente activa. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of tezepelumab on the centrally-read EoE EREFS 2. To evaluate the effect of tezepelumab on the centrally-read EoE-HSS 3. To evaluate the long-term effect of tezepelumab on the histologic response 4. To evaluate the long-term effect of tezepelumab on symptom improvement 5. To evaluate the long-term effect of tezepelumab on the centrally-read EoE EREFS 6. To evaluate the effect of tezepelumab on achievement of clinico-histological remission 7. To evaluate the effect of tezepelumab on peak eosinophil count 8. To evaluate the effect of tezepelumab on EoE symptoms in adolescents 9. To evaluate the long-term effect of tezepelumab |
1. Evaluar el efecto de tezepelumab sobre la EREFS de la EoE de lectura centralizada. 2. Evaluar el efecto de tezepelumab sobre el EoE-HSS de lectura centralizada. 3. Evaluar el efecto a largo plazo de tezepelumab sobre la respuesta histológica. 4. Evaluar el efecto a largo plazo de tezepelumab sobre la mejoría de los síntomas. 5. Evaluar el efecto a largo plazo de tezepelumab en la EREFS de la EoE de lectura centralizada. 6. Evaluar el efecto de tezepelumab sobre el logro de la remisión clínico-histológica. 7. Evaluar el efecto de tezepelumab sobre el recuento máximo de eosinófilos. 8. Evaluar el efecto de tezepelumab sobre los síntomas de la EoE en adolescentes. 9. Evaluar el efecto a largo plazo de tezepelumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participant must be 12 to 80 years of age inclusive, at the time of signing the informed consent/assent.
2. Weight ≥ 40 kg at Visit 1
3. Established diagnosis of EoE with a previous EGD and esophageal biopsy confirming a diagnosis of EoE.
4. Participants who have symptomatic EoE as defined by a history of on average at least 2 episodes of dysphagia (any severity of food going down slowly or being stuck in the throat) per week in the 4 weeks prior to Visit 1.
5. Must remain on a stabilized diet for at least 8 weeks prior to Visit 1 and during the course of the study (stable diet is defined as no initiation of single or multiple elimination diets or reintroduction of previously eliminated food groups).
6. May be on any background PPI and/or STC, during the course of the study, as long as background medications have been stable for at least 8 weeks prior to the screening/run-in period (Visit 1) and there is agreement not to change background medication or dosage unless medically indicated, during the screening/run-in and treatment period.
7. Participants currently leukotriene inhibitors and/or steroid treatments for asthma or allergies that are inhaled or administered intranasally, must report a stable dose for at least 4 weeks prior to the screening/run-in period (Visit 1).
8. If a medication for EoE (including PPI and/or STC) is discontinued prior to the screening/run-in, there should be a washout period of at least 8 weeks prior to Visit 1. Discontinuation of any marketed biologic (monoclonal or polyclonal antibody) should have a washout period of 4 months or 5 half-lives prior to Visit 1, whichever is longer.
9. Participants must have previously documented standard of care treatment, which could include PPI and/or STC and/or diet. |
1. El participante debe tener entre 12 y 80 años en el momento de firmar/asentir el consentimiento informado.
2. Peso ≥ 40 kg en la visita 1.
3. Diagnóstico establecido de EoE con una EGD (esofagogastroduodenoscopia) y biopsia esofágica previas que confirmen un diagnóstico de EoE.
4. Participantes que tienen EoE sintomática definida por un promedio de al menos 2 episodios de disfagia (cualquier nivel de gravedad de lentitud a la hora de tragar los alimentos o de que estos se queden atascados en la garganta) por semana en las 4 semanas anteriores a la visita 1.
5. Deben mantener una dieta estable durante al menos 8 semanas antes de la visita 1 y durante el transcurso del estudio (la dieta estable se define como la ausencia de inicio de dietas de eliminación de uno o múltiples grupos de alimentos o la reintroducción de grupos de alimentos previamente eliminados).
6. Puede estar en tratamiento de base con cualquier IBP (inhibidor de la bomba de protones) y/o CTD (corticoesteroide tópico deglutido) durante el transcurso del estudio, siempre que el tratamiento de base se haya mantenido estable durante al menos 8 semanas antes del período de selección/rodaje (visita 1) y haya un acuerdo de no cambiar la medicación de base ni la dosis, a menos que esté médicamente indicado, durante el período de selección/rodaje y tratamiento.
7. Los participantes que actualmente reciban tratamiento con inhibidores de leucotrienos y/o esteroides para el asma o las alergias que se inhalan o administran por vía intranasal deben informar de estar recibiendo una dosis estable durante al menos 4 semanas antes del período de selección/rodaje (visita 1).
8. Si se interrumpe el tratamiento con un medicamento para la EoE (incluidos IBP y/o CTD) antes de la selección/rodaje, debe haber un período de reposo farmacológico de al menos 8 semanas antes de la visita 1. La interrupción del tratamiento con cualquier producto biológico comercializado (anticuerpo monoclonal o policlonal) debe tener un período de reposo farmacológico de 4 meses o 5 semividas antes de la visita 1, lo que sea mayor.
9. Los participantes deben documentar haberse sometido previamente al tratamiento de referencia, que podría incluir IBP y/o CTD y/o dieta. |
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E.4 | Principal exclusion criteria |
1. Other gastrointestinal disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, celiac disease, eosinophilic enteritis, colitis, diverticulitis, irritable bowel syndrome, or other clinically significant gastrointestinal conditions as per Investigator discretion. 2.Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation at screening. 3. Use of a feeding tube, or having a pattern of not eating solid food daily. 4. Hypereosinophilic syndrome, defined by multiple organ involvement and persistent blood eosinophil count > 1500 eosinophils/μL 5. EGPA vasculitis 6. Esophageal dilation performed within 8 weeks prior to screening. |
1. Otros trastornos gastrointestinales, como infección activa por Helicobacter pylori, antecedentes de acalasia, varices esofágicas, enfermedad de Crohn, colitis ulcerosa, enfermedad inflamatoria intestinal, celiaquía, enteritis eosinofílica, colitis, diverticulitis, síndrome del intestino irritable u otras afecciones gastrointestinales clínicamente significativas a juicio del investigador.
2.Estenosis esofágica que impide el paso fácil de un endoscopio estándar o cualquier estenosis esofágica crítica que requiera dilatación en la selección.
3. Uso de una sonda de alimentación o tener un patrón de no comer alimentos sólidos a diario.
4. Síndrome hipereosinofílico, definido por afectación de múltiples órganos y recuento persistente de eosinófilos en sangre >1500 eosinófilos/µl.
5. Vasculitis de tipo EGPA.
6. Dilatación esofágica realizada en las 8 semanas anteriores a la selección. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels at Week 24 2. Change from baseline in DSQ score at Week 24 |
1. Respuesta histológica de recuento máximo de eosinófilos esofágicos por HPF de ≤6 en todos los niveles esofágicos disponibles en la semana 24. 2. Variación respecto al inicio en la puntuación DSQ en la semana 24. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Week 24 2. Week 24 |
1. Semana 24 2. Semana 24 |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in EoE EREFS at Week 24 and Week 52
2. Change from baseline in EoE-HSS grade score at Week 24 and Week 52
3. Change from baseline in EoE-HSS stage score at Week 24 and Week 52
4. Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels at Week 52
5. Change from baseline in DSQ score at Week 52
6. Response of achieving clinico-histological remission at Week 24 and Week 52
7. Change from baseline in peak esophageal eosinophil count (EOS/HPF) at Week 24 and Week 52
8. Changes from baseline in PEESS Module at Week 24 and Week 52 (adolescents only) |
1. Variación respecto al inicio en la escala EREFS de EoE en la semana 24 y la semana 52.
2. Variación respecto al inicio en la puntuación del grado HSS de EoE en la semana 24 y la semana 52.
3. Variación respecto al inicio en la puntuación del estadio HSS de EoE en la semana 24 y la semana 52.
4. Respuesta histológica de recuento máximo de eosinófilos esofágicos por HPF de ≤6 en todos los niveles esofágicos disponibles en la semana 52.
5. Variación respecto al inicio en la puntuación DSQ en la semana 52.
6. Respuesta para lograr la remisión clínico-histológica en la semana 24 y la semana 52.
7. Variación respecto al inicio en el recuento máximo de eosinófilos esofágicos (EOS/HPF) en la semana 24 y la semana 52.
8. Variación respecto al inicio en el módulo PEESS en la semana 24 y la semana 52 (solo adolescentes). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Varies depending on the endpoint/objective |
Varía en función del criterio de valoración / objetivo |
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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 | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 |
Brazil |
Canada |
China |
Israel |
Japan |
New Zealand |
United States |
Austria |
Finland |
Sweden |
Netherlands |
Spain |
Czechia |
Germany |
Greece |
Italy |
Belgium |
Denmark |
Norway |
Slovakia |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 9 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 10 |