E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Eosinophilic esophagitis (EoE) |
Esofagitis eosinofílica (EoE) |
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E.1.1.1 | Medical condition in easily understood language |
Eosinophilic esophagitis (EoE) is an inflammatory disease of the food pipe that involves eosinophils, a type of white blood cell. |
La esofagitis eosinofílica (EoE) es una enfermedad inflamatoria del conducto alimentario que involucra a los eosinófilos, un tipo de glóbulo blanco. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate efficacy of barzolvolimab, compared to placebo, in reducing esophageal intraepithelial infiltration of mast cells as assessed by peak esophageal intraepithelial mast cell (PMC) count in EoE patients |
Evaluar la eficacia de barzolvolimab, en comparación con placebo, en la reducción de la infiltración intraepitelial esofágica de mastocitos según lo evaluado por el recuento máximo de mastocitos intraepiteliales esofágicos (PMC) en pacientes con EoE |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of barzolvolimab, compared to placebo, in reducing symptoms of dysphagia as assessed by dysphagia symptom questionnaire (DSQ) in EoE patients • To evaluate efficacy of barzolvolimab, compared to placebo, in reducing esophageal intraepithelial infiltration of eosinophils as assessed by peak esophageal intraepithelial eosinophil (PEC) count in EoE patients • To evaluate the safety profile of barzolvolimab in EoE patients |
• Evaluar la eficacia de barzolvolimab, en comparación con placebo, en la reducción de los síntomas de disfagia según lo evaluado por el cuestionario de síntomas de disfagia (DSQ) en pacientes con EoE • Evaluar la eficacia de barzolvolimab, en comparación con placebo, en la reducción de la infiltración intraepitelial esofágica de eosinófilos según lo evaluado por el recuento máximo de eosinófilos intraepiteliales esofágicos (PEC) en pacientes con EoE • Evaluar el perfil de seguridad de barzolvolimab en pacientes con EoE |
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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 |
Dense Pharmacokinetic and Biomarker Sampling:
In addition to the PK sampling for all patients as per the protocol scheldue of assessments, dense sampling will occur at select sites during the Active Treatment Phase. This sampling will provide supplementary PK and PD data to better characterize the absorption of barzolvolimab and the kinetics of tryptase suppression in the study population. Dense sampling will be conducted at select centers in approximately 12 patients who consent. |
Muestreo denso de farmacocinética y biomarcadores:
Además del muestreo farmacocinético para todos los pacientes según el programa de evaluaciones del protocolo, se realizará un muestreo denso en sitios seleccionados durante la fase de tratamiento activo. Este muestreo proporcionará datos complementarios de farmacocinética y farmacocinética para caracterizar mejor la absorción de barzolvolimab y la cinética de supresión de triptasa en la población de estudio. Se realizará un muestreo denso en centros seleccionados en aproximadamente 12 pacientes que den su consentimiento. |
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E.3 | Principal inclusion criteria |
1. Read, understood, and provided written informed consent, after the nature of the study has been fully explained. 2. Male or female, ≥ 18 years of age at the time of signing the informed consent. 3. Documented diagnosis of EoE by endoscopy. 4. Esophageal intraepithelial eosinophilic infiltration, with peak esophageal intraepithelial eosinophil count (PEC) of ≥ 15 per high power field (hpf) from at least 2 of 3 levels (proximal, mid, and distal) of the esophagus at the Screening/Baseline esophagogastroduodenoscopy (EGD) at the Screening Visit. 5. Must be symptomatic, defined as: a. History (by patient report) of an average of at least 2 days per week with dysphagia with intake of solid foods during 1 month prior to the Screening Visit and b. At least 4 days with dysphagia (answer of “Yes” to DSQ Question #2) within the last 2 weeks immediately prior to randomization. 6. Must have been on a stable diet which includes solid foods for at least 2 months prior to the Screening Visit and throughout the study. Note: Stable diet is defined as no initiation or elimination of single or multiple food groups or reintroduction of previously eliminated food groups. 7. Have had inadequate response to or is inappropriate for and/or intolerant to a standard-of-care treatment for EoE (e.g., PPI, swallowed topical corticosteroids, or dietary elimination) based on the investigator’s clinical judgment. |
1. Leer, comprender y dar su consentimiento informado por escrito, después de que se haya explicado completamente la naturaleza del estudio. 2. Hombre o mujer, ≥ 18 años de edad al momento de firmar el consentimiento informado. 3. Diagnóstico documentado de EoE por endoscopia. 4. Infiltración eosinófila intraepitelial esofágica, con un recuento máximo de eosinófilos intraepiteliales esofágicos (PEC) de ≥ 15 por campo de alta potencia (hpf) de al menos 2 de 3 niveles (proximal, medio y distal) del esófago en la esofagogastroduodenoscopia inicial/de detección (EGD) en la visita de selección. 5. Debe ser sintomático, definido como: una. Antecedentes (por informe del paciente) de un promedio de al menos 2 días por semana con disfagia con ingesta de alimentos sólidos durante 1 mes antes de la Selección Visita y b. Al menos 4 días con disfagia (respuesta "Sí" a la pregunta n.º 2 de DSQ) en las últimas 2 semanas inmediatamente antes de la aleatorización. 6. Debe haber seguido una dieta estable que incluya alimentos sólidos durante al menos 2 meses antes de la visita de selección y durante todo el estudio. Nota: La dieta estable se define como la no iniciación o eliminación de uno o varios grupos de alimentos o la reintroducción de grupos de alimentos previamente eliminados. 7. Ha tenido una respuesta inadecuada o es inapropiado y/o intolerante a un tratamiento estándar de atención para la EoE (p. ej., PPI, corticosteroides tópicos ingeridos o eliminación dietética) según el juicio clínico del investigador. |
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E.4 | Principal exclusion criteria |
1. Diagnosis of hypereosinophilic syndrome or Churg-Strauss syndrome (or eosinophilic granulomatosis with polyangiitis). 2. History of a clinicopathologic diagnosis of eosinophilic gastritis or eosinophilic duodenitis. 3. Known active Helicobacter pylori infection. 4. History of coagulation disorders or esophageal varices. 5. History of achalasia, Crohn’s disease, ulcerative colitis or celiac disease. 6. Esophageal dilation within 3 months prior to the Screening Visit. 7. Avoiding solid foods or using feeding tube. 8. Non-biologic systemic (oral or injectable) agents within 2 months prior to the Screening Visit. 9. Biologic therapy within 3 months or 5 half-lives, whichever is longer, prior to the Screening Visit. Note: Biologic agents include but are not limited to interleukin (IL)-4 receptor inhibitor (dupilumab), IL-5 inhibitors (e.g., mepolizumab, benralizumab), IL-13 inhibitors (e.g., tralokinumab, lebrikizumab), anti-IgE (e.g., omalizumab), IFN-γ inhibitors, or other approved or investigational biologics. 10. Diagnosis of idiopathic anaphylaxis or other severe allergic reactions that in the opinion of the investigator, could increase the patient’s risk for systemic hypersensitivity reactions; or any known contraindications or hypersensitivity to any component of study treatments, drugs of similar chemical classes (i.e., to murine, chimeric or human antibodies) or antihistamines. 11. Women who are pregnant or nursing. All female patients with reproductive potential must have a negative pregnancy test prior to starting study treatment. |
1. Diagnóstico de síndrome hipereosinofílico o síndrome de Churg-Strauss (o granulomatosis eosinofílica con poliangitis). 2. Antecedentes de diagnóstico clinicopatológico de gastritis eosinofílica o duodenitis eosinofílica. 3. Infección activa conocida por Helicobacter pylori. 4. Antecedentes de trastornos de la coagulación o várices esofágicas. 5. Antecedentes de acalasia, enfermedad de Crohn, colitis ulcerosa o enfermedad celíaca. 6. Dilatación esofágica dentro de los 3 meses anteriores a la visita de selección. 7. Evitar alimentos sólidos o usar sonda de alimentación. 8. Agentes sistémicos no biológicos (orales o inyectables) dentro de los 2 meses anteriores a la visita de selección. 9. Terapia biológica dentro de los 3 meses o 5 semividas, lo que sea más largo, antes de la visita de selección. Nota: Los agentes biológicos incluyen, entre otros, inhibidores del receptor de interleucina (IL)-4 (dupilumab), inhibidores de IL-5 (p. ej., mepolizumab, benralizumab), inhibidores de IL-13 (p. ej., tralokinumab, lebrikizumab), anti-IgE ( ej., omalizumab), inhibidores de IFN-γ u otros productos biológicos aprobados o en investigación. 10. Diagnóstico de anafilaxia idiopática u otras reacciones alérgicas graves que, en opinión del investigador, podrían aumentar el riesgo del paciente de sufrir reacciones de hipersensibilidad sistémica; o cualquier contraindicación conocida o hipersensibilidad a cualquier componente de los tratamientos del estudio, fármacos de clases químicas similares (es decir, a anticuerpos murinos, quiméricos o humanos) o antihistamínicos. 11. Mujeres embarazadas o lactantes. Todas las pacientes con potencial reproductivo deben tener una prueba de embarazo negativa antes de comenzar el tratamiento del estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Absolute change from baseline to Week 12 in the PMC/high power field (hpf) |
• Cambio absoluto desde el inicio hasta la semana 12 en el campo de PMC/alta potencia (hpf) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening (baseline), week 12 |
Cribado (línea basal), semana 12 |
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E.5.2 | Secondary end point(s) |
• Absolute changes from baseline to Week 12 in DSQ • Absolute change from baseline to Week 12 in PMC/hpf among patients with baseline PMC ≥ 12/hpf • Absolute change from baseline to Week 12 in PEC/hpf • Percent (%) change from baseline to week 12 in PMC7hpf • Incidence of TEAEs |
• Cambios absolutos desde el inicio hasta la semana 12 en DSQ • Cambio absoluto desde el inicio hasta la semana 12 en PMC/hpf entre pacientes con PMC inicial ≥ 12/hpf • Cambio absoluto desde el inicio hasta la semana 12 en PEC/hpf • Cambio porcentual (%) desde el inicio hasta la semana 12 en PMC7hpf • Incidencia de TEAE |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Screening (baseline), week 12
TEAEs: continuously until end of study visit. |
Cribado (línea basal), semana 12
TEAE: continuamente hasta el final de la visita de estudio. |
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Canada |
United States |
Germany |
Italy |
Poland |
Spain |
United Kingdom |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
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 | 2 |