E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe atopic dermatitis |
Dermatitis atópica de moderada a grave. |
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E.1.1.1 | Medical condition in easily understood language |
Inflammation of the skin resulting in itchy, red, swollen and cracked skin. |
Inflamacion de la piel produciendo picor, enrojecimiento, inflamación y grietas en la piel. |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
E.1.2 | System Organ Class | 100000004858 |
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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 characterize the dose-response relationship of ZPL389 in patients with moderate to severe AD assessed by Investigator's global assessment (IGA) response at week 16 . |
Caracterizar la relación dosis-respuesta de ZPL389 en sujetos con dermatitis atópica de moderada a grave mediante la evaluación global del investigador de la respuesta en la semana 16. |
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E.2.2 | Secondary objectives of the trial |
- To characterize the dose-response relationship of ZPL389 in patients with moderate to severe AD assessed using the percent change from baseline in Eczema Area and Severity Index (EASI) score after 16 weeks of treatment - To evaluate the efficacy across different dose levels as assessed by EASI and IGA compared to placebo over time - To assess the safety and tolerability of different doses of ZPL389 as compared to placebo |
- Caracterizar la relación dosis-respuesta de ZPL389 en sujetos con dermatitis atópica de moderada a grave evaluada según el cambio porcentual respecto a la basal en el índice de extensión y gravedad del eccema o DA después de 16 semanas de tratamiento. - Evaluar la eficacia en los diferentes niveles de dosis según el Eczema Area and Severity Index y la evaluación global por parte del investigador en comparación con placebo a lo largo del tiempo. - Evaluar la seguridad y la tolerabilidad de diferentes dosis de ZPL389 en comparación con placebo. |
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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 |
Title: Actigraphy substudy Objective: Explore the effect of ZPL389 on sleep disturbance and nocturnal scratching in a subset of subjects.
Optional tape strips sub-study was added to assess biomarkers and molecular pathways related to disease from superficial skin layers. |
Titulo: sub-estudio Actígrafo Objetivo: Explorar los efectos de ZPL389 en los transtornos del sueño y rascado nocturno en un subconjunto de sujetos.
Se añaden tiras de cintas opcionales para medir los biomarcadores y vias moleculares relacionados con la enfermedad de las capas superficiales de la piel. |
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E.3 | Principal inclusion criteria |
Eligible for inclusion in this study must fulfill all of the following criteria: - Written informed consent - Females and males aged 18 years or older - Chronic atopic dermatitis (according to AADConsensus Criteria), that has been present for at least 1 year before the Baseline visit. - Moderate to severe atopic dermatitis defined as: - Eczema Area and Severity Index >=16 at Screening and at Baseline - Investigator's global assessment 3 or 4 on a 5-point scale (at screening and Baseline) - Body Surface Area involvement >=10% at Screening and Baseline - Average peak pruritis score >=3 as assessed by NRS over the last 7 days prior to Baseline - Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks) - Candidate for systemic treatment - Have applied a stable dose of bland topical emollient at least once daily for at least the 7 consecutive days immediately before the baseline visit |
Para ser elegible para la inclusión en este estudio tiene que cumplir todos los criterios siguientes: - Consentimiento informado por escrito. - Dermatitis atópica crónica (según los criterios de consenso de la American Academy of Dermatology) que haya estado presente durante al menos un año antes de la basal. - La dermatitis atópica de moderada a grave se define como: - Eczema Area and Severity Index >=16 en la selección y en la basal. - Evaluación global del investigador de 3 ó 4 en una escala de 5 puntos (en la selección y en la basal). - Area de superficie corporal afectada >=10 % en la selección y en la basal. - Media de la puntuación máxima del prurito >=3 en la escala numérica durante los últimos 7 días anteriores a la basal - Antecedentes recientes documentados (durante los 6 meses anteriores a la visita de selección) de respuesta inadecuada al tratamiento con medicamentos tópicos o sujetos a quienes no se aconsejen los tratamientos tópicos desde el punto de vista médico (p. ej., debido a efectos secundarios importantes o por riesgos de seguridad). - Candidatos a tratamiento sistémico. - Haber aplicado una dosis estable de emoliente tópico suave al menos una vez al dia durante al menos 7 dias consecutivos inmediatamente antes de la visita basal |
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E.4 | Principal exclusion criteria |
- Any skin disease that, in the opinion of the investigator, including infection, would confound the diagnosis or evaluation of atopic dermatitis disease activity - Current active skin infection at Baseline - Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days /until the expected pharmacodynamic effect has returned to baseline, whichever is longer. - History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes. - subjects taking prohibited medication as per protocol - Risk factors for Torsades de Pointe including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia or any of the following: - Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome - Concomitant medication(s) with a "Known Risk of Torsades de Pointe" that cannot be discontinued or replaced by safe alternative medication. - Resting QTcF >=450 msec (male) or >=470 msec (female) at screening or baseline or inability to determine the QTcF interval - Cardiac or cardiac repolarization abnormality - Subjects with pre-existing conditions that may confound ability to diagnose drug-induced liver injury or subjects with factors that increase susceptibility to DILI - Subjects who have a laboratory abnormality at Screening - History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years - Past medical history record of, or current infection with, human immunodeficiency virus - Any surgical, medical, psychiatric or additional physical condition that the Investigator feels may jeopardize the subject in case of participation in this study - Pregnant or nursing (lactating) women - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using required methods of contraception during dosing and for 4 weeks after stopping of investigational medication. - Sexually active males unless they use a condom during intercourse while taking drug and for 120 days after stopping investigational medication and should not father a child in this period. - Prior exposure to ZPL389 treatment |
- Cualquier enfermedad cutánea, incluida la infección, que a criterio del investigador pueda confundir el diagnóstico o la evaluación de la actividad de la dermatitis atópica. - Actual infección activa de piel en el momento Basal - Uso de cualquier otro fármaco en investigación durante 5 vidas medias o durante 30 días antes del reclutamiento/hasta que el efecto farmacodinámico previsto haya vuelto al nivel basal, aquel periodo que sea más largo. - Antecedentes de hipersensibilidad a alguno de los componentes del fármaco del estudio o a fármacos de clases químicas similares. - Factores de riesgo de Torsades de Pointes (TdP), incluida hipopotasemia o hipomagnesemia no corregidas, antecedentes de insuficiencia cardíaca o antecedentes de bradicardia clínicamente significativa/sintomática, o cualquiera de los siguientes: - Síndrome de QT largo, antecedentes familiares de muerte súbita idiopática o síndrome del segmento QT largo congénito. - Medicación concomitante con "riesgo conocido de Torsades de Pointes" que no pueda discontinuarse ni sustituirse por medicación alternativa segura. - QTcF en reposo >=450 mseg (hombre) o >=470 mseg (mujer) en la selección o en la basal o incapacidad para determinar el intervalo QTcF. - Anomalía cardíaca o de la repolarización cardíaca. - Sujetos con enfermedades ya existentes que puedan confundir la capacidad de diagnosticar el daño hepático inducido por fármacos (DHIF) o sujetos con factores que aumenten la susceptibilidad al DHIF. - Sujetos que tienen una anomalía de laboratorio en la selección - Antecedentes de enfermedad linfoproliferativa o cualquier malignidad conocida o antecedentes de malignidad de cualquier órgano sistémico en los últimos 5 años. - Historial médico o infección actual con el virus de inmunodeficiencia humana - Cualquier condición quirúrgica, médica, psiquiátrica o física adicional que el investigador considere que puede poner en peligro al sujeto en caso de participar en este estudio. - Mujeres embarazadas o lactantes - Mujeres en edad fértil, definidas como todas las mujeres fisiológicamente capaces de quedarse embarazadas, a menos que estén utilizando los métodos anticonceptivos necesarios durante el tratamiento y durante 4 semanas después de suspender la medicación en investigación. - Hombres sexualmente activos a menos que usen un condón durante las relaciones sexuales mientras toman la medicación y durante 120 días después de suspender la medicación en investigación y no deben engendrar un hijo en este período -Participación en estudios previos de ZPL389. |
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E.5 End points |
E.5.1 | Primary end point(s) |
IGA response at Week 16 |
Respuesta del IGA en la semana 16 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Percent change from baseline EASI score at Week 16 • At each visit: • IGA score • IGA response • EASI score as well as absolute and percent change from baseline EASI score • EASI 50 response, EASI 75 response • Frequency of adverse events |
- Porcentaje de cambio en la escala EASI desde la basal a la semana 16 - En cada visita: - Escala IGA - Respuesta IGA - Escala EASI, asi como el cambio absoluto y porcentaje en la escala EASI desde la basal - Respuesta EASI 50, respuesta EASI 75 - Frecuencia de acontencimientos adversos |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At visits in week 0, 2, 4, 6, 8, 12, 16 |
En las visita de la semana 0, 2, 4, 6, 8, 12, 16 |
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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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Actigraphy Substudy : A subset of approximately 100-150 subjects will participate in a substudy to measure movement during sleep. |
Sub-estudio actígrafo: Un subconjunto de aproximadamente 100-150 sujetos participaran en un sub-estudio para medir el movimiento durante el sueño. |
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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 | 5 |
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 | 64 |
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 |
Austria |
Belgium |
Canada |
Czech Republic |
Estonia |
Finland |
France |
Germany |
Hungary |
Iceland |
Japan |
Latvia |
Lithuania |
Netherlands |
Poland |
Russian Federation |
Slovakia |
Spain |
Taiwan |
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 |
Ultima visita del ultimo sujeto |
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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 | 1 |
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 | 3 |