E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Plaque-Type Psoriasis |
Psoriasis en placa de moderada a grave |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037153 |
E.1.2 | Term | Psoriasis |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue 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 |
To evaluate the efficacy of guselkumab compared with secukinumab for the treatment of subjects with moderate to severe plaque-type psoriasis. |
Evaluar la eficacia de guselkumab frente a secukinumab para el tratamiento de sujetos con psoriasis en placa de moderada a grave |
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E.2.2 | Secondary objectives of the trial |
- The safety and tolerability of guselkumab in subjects with moderate to severe plaque-type psoriasis. - The PK and immunogenicity of guselkumab after subcutaneous (SC) administrations in subjects with moderate to severe plaque-type psoriasis. |
- La seguridad y la tolerabilidad de guselkumab en pacientes con psoriasis en placa de moderada a grave. - La FC y la inmunogenicidad de guselkumab tras su administración subcutánea (s.c.) en pacientes con psoriasis en placa de moderada a grave. |
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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 |
3 optional substudies are planned: skin biopsy, mucosal inflammation and genetic analysis. 1) Skin biopsies: will be collected in a subset of subjects at selected sites who consent to participate in the optional skin biopsy substudy to determine gene expression profiles and cellular content associated with response to guselkumab or secukinumab. Epigenetic evaluation may be conducted on skin samples obtained in the biopsy substudy. These exploratory analyses of psoriatic skin lesions may help to further define the cellular and molecular mechanism of action associated with blockade of IL-23 compared to blockade of IL-17A in psoriasis. Fecal samples will be collected in a subset of subjects that consent to participate in the optional mucosal inflammation substudy to assess inflammatory profiles in response to treatment with guselkumab or secukinumab. Spain is not going to participate in this substudy. 2) Mucosal inflammation: the objective of this substudy is to determine the impact of blocking IL-23 compared to blocking IL-17A on inflammatory proteins that may be present in fecal samples as surrogate markers of subclinical inflammation derived from intestinal mucosal tissue. 3) Genetic Analysis: it is recognized that genetic variation can be an important contributory factor to inter-individual differences in drug distribution and response and can also serve as a marker for disease susceptibility and prognosis. Genetic (DNA) analysis may help to explain inter-individual variability in clinical outcomes and may help to identify population subgroups that respond differently to a drug. The goal of the genetic (DNA) analysis is to collect a single DNA sample (from whole blood) to allow the identification of genetic factors, including single nucleotide polymorphisms, that may influence the PD effects, efficacy, or tolerability of guselkumab and secukinumab, and to identify genetic factors associated with psoriasis. Epigenetic evaluation may be conducted on skin samples obtained in the biopsy substudy to assess potential epigenetic modifications associated with different immune cell infiltrates in psoriatic skin lesions. Only subjects who sign the consent form to participate in the genetic assessment will have whole blood DNA or skin samples collected. |
Están planeados tres sub estudios opcionales: biopsias de piel, inflamación de la mucosa y análisis genético 1)Biopsia de piel. Será obtenidas a un sub conjunto de pacientes seleccionados por centros que consientan participar en el sub estudio opcional de biopsias de piel, para determinar el contenido de los perfiles de expresión genética y celular asociado a respuestas con Guselkumab o Secukinumab. La evaluación epigenética deberá ser llevada a cabo en las muestras de piel obtenidas en el sub estudio de biopsias. Esta investigación exploratoria de las lesiones psoriásicas de la piel podría ayudar en el futuro a definir un mecanismo de acción celular y molecular asociado a un bloqueo del IL-23 comparado con el bloquedo del IL-17ª en psoriasis. Las muestras de heces serán recogidas en un subgrupo de pacientes que consientan participar en el sub estudio opcional de inflamación de mucosa para medir los perfiles de inflamación en respuesta al tratamiento con Guselkumab o Secukinumab. España no participa en este sub-estudio 2)Inflamación de la mucosa: El objetivo de este sub estudio es determinar el impacto del bloqueo de IL-23 comparado con el bloqueo en IL-17ª en proteinas inflamatorias que puedan presentarse en muestras fecales como marcadores de inflamación subclínica derivadas de tejído blando en la mucosa intestinal. 3)Análisis genético: Se reconoce que la variación genética puede ser un importante factor contribuyente en las diferencias interindividuales en la distribución y respuesta de los fármacos y también puede servir como un marcador para la susceptibilidad a la enfermedad y el pronóstico. El análisis genético (ADN) puede ayudar a explicar la variabilidad interindividual en los resultados clínicos y puede ayudar a identificar subgrupos de población que responden de manera diferente a un fármaco. El objetivo del análisis genético (ADN) es obtener una sola muestra de ADN (de sangre completa) para permitir la identificación de factores genéticos, incluyendo polimorfismos de un solo nucleótido, que pueden influir en los efectos farmacodinámicos, la eficacia o tolerabilidad de guselkumab y secukinumab, y para identificar los factores genéticos asociados con la psoriasis. La evaluación epigenética puede realizarse en muestras de piel obtenidas en el subestudio de biopsia para evaluar posibles modificaciones epigenéticas asociadas con diferentes infiltrados de células inmunes en lesiones cutáneas psoriásicas. Sólo se obtendrán muestras de los sujetos que firmen el consentimiento para participar en la evaluación genética de ADN de sangre completa o muestras de piel. |
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E.3 | Principal inclusion criteria |
1. Be a man or a woman at least 18 years of age 2. Have a diagnosis of plaque-type psoriasis for at least 6 months before the first administration of study drug. 3. Have a PASI ≥12 at screening and at baseline. 4. Have an IGA ≥3 at screening and at baseline. 5. Have an involved BSA ≥10% at screening and at baseline. 6. Be a candidate for phototherapy or systemic treatment for psoriasis 7. Be considered, in the opinion of the investigator, suitable candidates for secukinumab (Cosentyx) therapy according to their country's approved secukinumab product labeling.
Reproduction-related inclusion criteria: 8. Before the first administration of study drug, a woman must be either: - Not of childbearing potential: premenarchal; postmenopausal; permanently sterilized or otherwise be incapable of pregnancy. - Of childbearing potential and practicing a highly effective method of birth control, consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies 9. A woman of childbearing potential must have a negative urine pregnancy test at screening and at Week 0 and agree to urine pregnancy testing before receiving injections. 10. A woman must agree not to donate eggs for the purposes of assisted reproduction during the study and for at least 16 weeks after receiving the last administration of secukinumab or at least 12 weeks after receiving the last administration of guselkumab. 11. A man who is sexually active with a woman of childbearing potential and who has not had a vasectomy must agree to use a barrier method of birth control or a partner with an occlusive cap during the study and for at least 16 weeks after receiving the last administration of secukinumab or at least 12 weeks after receiving the last administration of guselkumab. All men must also agree to not donate sperm during the study and for at least 16 weeks after receiving the last administration of secukinumab or at least 12 weeks after receiving the last administration of guselkumab.
Infectious disease-related inclusion criteria: 12. Are considered eligible according to the following TB screening criteria: - Have no history of latent or active TB before screening. o An exception is made for subjects who have a history of latent TB and - are currently receiving treatment for latent TB, - will initiate treatment for latent TB before the first administration of study drug, - or have documentation of having completed appropriate treatment for latent TB within 5 years before the first administration of study drug. o It is the responsibility of the investigator to verify the adequacy of previous anti-TB treatment and provide appropriate documentation. - Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination. - Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB before the first administration of study drug. - Within 2 months before the first administration of study drug, have a negative QuantiFERON®-TB Gold test result, or have a newly identified positive QuantiFERON-TB Gold test result in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated before the first administration of study drug. Within 2 months before the first administration of study drug, a negative tuberculin skin test, or a newly identified positive tuberculin skin test in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated before the first administration of study drug, is additionally required if the QuantiFERON-TB Gold test is not approved/registered in that country or the tuberculin skin test is mandated by local health authorities. Have a chest radiograph, taken within 3 months before the first administration of study drug and read by a qualified radiologist, with no evidence of current, active TB or old, inactive TB.
Please refer to protocol pages 24-27 for all the inclusion criteria |
1.Hombre o mujer mayor de 18 años 2.Tener un diagnóstico de Psoriasis en placa desde al menos 6 meses antes de la primera administración del medicamento en investigación. 3.Tener un PASI ≥12 en screening y en basal 4.Tener un IGA ≥3en screening y en basal 5.Tener un BSA ≥10% en screening y en basal 6.Ser candidato a fototerapia o tratamientos sistémicos para psoriasis 7.Ser considerado, en opinión del investigador, adecuado candidato para tratamiento con Secukinimab (Cosentyx) según el etiquetado del producto aprobado en su país. Criterios de inclusión relacionados con la reproducción: 8- Antes de la primera administración del fármaco, las mujeres deben cumplir:Mujeres que no estén en edad fértil: Premenárquicas, posmenopáusicas, estériles o que no puedan quedarse embarazadas.Que se hayan realizado una radiografía dentro de los tres meses anteriores a la primera dosis de tratamiento, evaluada por un radiólogo, sin evidencia de tuberculosis activa ni de tuberculosis inactivada. Consulte las páginas 24-27 del protocolo para conocer todos los criterios de inclusión 10. Una mujer debe comprometerse a no donar óvulos con fines de reproducción asistida durante el estudio y durante al menos 16 semanas después de recibir la última administración de secukinumab o al menos 12 semanas después de recibir la última administración de guselkumab. 11. Un hombre que es sexualmente activo con pareja en edad fértil y al que no se le haya practicado una vasectomía debe acordar usar un método anticonceptivo de barrera durante el estudio y durante al menos 16 semanas después de recibir la última administración de secukinumab o al menos 12 semanas después de recibir la última administración de guselkumab. Todos los hombres también deben aceptar no donar esperma durante el estudio y durante al menos 16 semanas después de recibir la última administración de secukinumab o al menos 12 semanas después de recibir la última administración de guselkumab.Criterios de inclusión relacionados con las enfermedades infecciosas: 12. Se consideran elegibles de acuerdo con los siguientes criterios de selección de Tuberculosis: - No tener antecedentes de tuberculosis latente o activa antes del Screening. - Se permite la excepción para los sujetos que tienen antecedentes de TB latente y están recibiendo tratamiento para la tuberculosis latente, - iniciarán el tratamiento de la tuberculosis latente antes de la primera administración del fármaco del estudio, - tener documentación de haber completado el tratamiento adecuado para la TB latente dentro de los 5 años anteriores a la primera administración del medicamento del estudio. - Es responsabilidad del investigador verificar la idoneidad del tratamiento anti-TB anterior y proporcionar la documentación apropiada. - No tener signos o síntomas sugestivos de TB activa en la historia clínica y / o examen físico. - No haber tenido contacto reciente con una persona con TB activa o, si ha habido tal contacto, será remitido a un médico especializado en TB para someterse a una evaluación adicional y, si es necesario, recibir tratamiento adecuado para la TB latente antes de la primera administración Del fármaco del estudio. Consulte las páginas 24-27 del protocolo para todos los criterios de inclusión |
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E.4 | Principal exclusion criteria |
1. Has a history or current signs or symptoms of severe, progressive, or uncontrolled renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances. 2. Has unstable cardiovascular disease, defined as a recent clinical deterioration in the last 3 months or a cardiac hospitalization within the last 3 months. 3. Has unstable suicidal ideation or suicidal behavior, that may be defined as an eC-SSRS rating at screening of: Suicidal ideation with intention to act (“4”), Suicidal ideation with specific plan and intent (“5”), or a suicide attempt in the last 6 months and is confirmed to be at risk by the investigator based on an evaluation by a mental health professional. The final decision on excluding a subject will be made at the judgment of the investigator. 4. Has a transplanted organ (with exception of a corneal transplant >3 months before the first administration of study drug). 5. Has a history of an infected joint prosthesis, or has received antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced. 6. Is pregnant, nursing, or planning a pregnancy while enrolled in this study and within 12 weeks following the last administration of study drug. 7. Has a nonplaque form of psoriasis 8. Has current drug-induced psoriasis 9. Has had major surgery within 8 weeks before screening, or will not have fully recovered from such surgery, or has such surgery planned during the time the subject is expected to participate in the study. 10. Is known to have had a substance abuse (drug or alcohol) problem within the previous 12 months. 11. Had a known allergy or sensitivity to products containing latex.
Please refer to protocol pages 27-30 for all the exclusion criteria |
1.Tener antecedentes o signos o síntomas actuales de trastornos severos renales, cardíacos, vasculares, pulmonares, gastrointestinales, endocrinos, neurológicos, hematológicos, reumatológicos, psiquiátricos o metabólicos severos, progresivos o incontrolados. 2.Tener enfermedad cardiovascular inestable, definida como un deterioro clínico reciente en los últimos 3 meses o una hospitalización cardíaca en los últimos 3 meses. 3.Tener ideas suicidas inestables o conducta suicida, que pueda definirse con una calificación eC-SSRS en la selección de: Ideación suicida con intención de actuar ("4"), Ideación suicida con intención específica ("5") o intento de suicidio en los últimos 6 meses o confirmación de situación de riesgo por el investigador basado en una evaluación por un profesional de salud mental. La decisión final sobre la exclusión del paciente se hará a juicio del investigador. 4.Tener un órgano trasplantado (con excepción de un trasplante de córnea> 3 meses antes de la primera administración del fármaco del estudio) 5.Tener antecedentes de una prótesis articular infectada, o haber recibido antibióticos para una sospecha de infección de una prótesis articular, si esa prótesis no ha sido eliminada o reemplazada. 6.Mujeres embarazadas, en periodo de lactancia o planeando un embarazo durante el periodo de screening del estudio y dentro de las 12 semanas siguientes a la última administración del medicamento de estudio. 7.No diagnostico de psoriasis en placa 8.Tener psoriasis inducida por fármacos 9.Haber tenido una cirugía mayor dentro de las 8 semanas antes del screening, o no haberse recuperado completamente de tal cirugía, o tener planificada cirugía durante el tiempo en que el paciente va a participar en el estudio. 10.Conocimiento de un problema de abuso de sustancias (drogas o alcohol) en los 12 meses anteriores. 11.Tener una alergia conocida o sensibilidad a los productos que contengan látex. Para todos los criterios de exclusión, por favor revisar las páginas 27-30 del protocolo |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in this study is the proportion of subjects who achieve a PASI 90 response at Week 48, comparing the guselkumab group and the secukinumab group. |
El criterio primario a valorar en este estudio es la proporción de pacientes que logran una respuesta de PASI 90 en la semana 48, comparando con el grupo de guselkumab y el grupo de secukinumab. |
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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) |
The major secondary endpoints to compare the guselkumab group and the secukinumab group are listed below and are the proportion of subjects who achieve: - A PASI 75 response at both Week 12 and Week 48. - A PASI 90 response at Week 12. - A PASI 75 response at Week 12. - A PASI 100 response at Week 48. - An IGA score of cleared (0) at Week 48. |
El criterio secundaroi a valorar en este estudio a comparar entre los grupos de guselkumab y Secukinumab son: - Una respuesta PASI 75 para ambos en la semana 12 y semana 48 - Una repuesta PASI 90 en la semana 12 - Una respuesta PASI 75 en la semana 12 - Una respuesta PASI 100 en la semana 48 - Una puntuación IGA (0) en la semana 48 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 12 and 48 |
Semana 12 y 48 |
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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 | 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 | No |
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 |
Czech Republic |
France |
Germany |
Hungary |
Poland |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |