E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Plaque Type Psoriasis |
Soriasis en placa de moderada a grave |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 17.0 |
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 |
|
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 in the treatment of subjects with moderate to severe plaque-type psoriasis. ? To assess the safety and tolerability of guselkumab in subjects with moderate to severe plaque-type psoriasis. |
Evaluar la eficacia de guselkumab en el tratamiento de pacientes con psoriasis en placa de moderada a grave Evaluar la seguridad y tolerabilidad de guselkumab en pacientes con psoriasis en placa de moderada a grave |
|
E.2.2 | Secondary objectives of the trial |
? To compare the efficacy of guselkumab to adalimumab in subjects with moderate to severe plaque-type psoriasis. ? To evaluate the maintenance of response to guselkumab in subjects continuing on a 100 mg q8w regimen compared with the maintenance of response in subjects who have active treatment withdrawn. ? To evaluate the effect of treatment with guselkumab on other measures of signs and symptoms of psoriasis. ? To evaluate the effect of treatment with guselkumab on health-related quality of life and health economic outcomes. |
Para comparar la eficacia de guselkumab a adalimumab en pacientes con psoriasis en placa de moderada a grave. Para evaluar el mantenimiendo de la respuesta a guselkumab en los pacientes que continúan con una pauta de 100 mg c8s en comparación con elmantenimiento de la respuesta en los pacietnes a los que se retira el tratamiento activo. Para evaluar el efecto del tratamiento con guselkumab en otras medidas de signos y síntomas de la psoriasis. Para evaluar el efecto del tratamiento con guselkumab en la calidad relacionada con la salud de los resultados económicos de vida y salud. |
|
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 |
Skin biopsy samples will be collected from a subset of subjects who consent to participate in the optional biopsy substudy. Enrollment in the biopsy study will be optional and will include approximately 120 to 150 subjects at selected study sites. Only subjects who consent to participate in the optional biopsy substudy will undergo collection of these samples. Biopsies will be used for assessment of gene expression and T cell repertoire. Whole blood samples will be collected from the subset of subjects who consent to participate in the optional biopsy substudy. Peripheral blood mononuclear cells (PBMCs) will be isolated from these samples and processed for immune repertoire analysis with assessment of T-cell receptor clonality. Overview photographs of the whole body as well as photographs of selected psoriatic skin lesions will be taken at a subset of study sites in patients who provide an additional consent. Protocol A0, dated 10 July 2014 |
Muestras de biopsia de piel se recogerán a partir de un subgrupo de sujetos que den su consentimiento para participar en el subestudio biopsia opcional. La inscripción en el estudio de la biopsia será opcional e incluirá aproximadamente 120 a 150 sujetos en los sitios de estudio seleccionados. Sólo los sujetos que den su consentimiento para participar en el subestudio biopsia opcional se someterán a la recolección de estas muestras. Las biopsias se utilizarán para la evaluación de la expresión génica y repertorio de células T. Las muestras de sangre se recogerán desde el subgrupo de sujetos que den su consentimiento para participar en el subestudio biopsia opcional. Células mononucleares de sangre periférica (PBMCs) se aislaron de estas muestras y se procesaron para análisis repertorio inmune con la evaluación de la clonalidad de células T del receptor. Resumen fotografías de todo el cuerpo, así como fotografías de las lesiones cutáneas psoriásicas seleccionados serán tomadas en un subconjunto de los sitios de estudio en los pacientes que prestan un consentimiento adicional. Protocolo A0, de fecha 10 de julio 2014 |
|
E.3 | Principal inclusion criteria |
-Have a diagnosis of plaque-type psoriasis (with or without psoriatic arthritis) at least 6 months before the first administration of study agent - Have a Psoriasis Area and Severity Index (PASI) greater than or equal to (>=) 12 at Screening and at Baseline - Have an Investigator?s Global Assessment (IGA) score >=3 at Screening and at Baseline - Have an involved body surface area (BSA) >=10 percent (%) at Screening and at Baseline - Must be a candidate for either systemic therapy or phototherapy for psoriasis |
Tener un diagnóstico de la psoriasis de placas (con o sin artritis psoriásica) por lo menos 6 meses antes de la primera administración del fármaco del estudio Tener un Psoriasis Area and Severity Index (PASI) mayor o igual que (> =) 12 en la selección y en la visita basal - Tener una (IGA) Resultado de Evaluación Global del Investigador> = 3 en la selección y en la línea de base - ¿Tienes una superficie corporal involucrada (BSA)> = 10 por ciento (%) en la selección y en la línea de base - Debe ser un candidato para cualquiera de las terapias sistémicas o fototerapia para la psoriasis |
|
E.4 | Principal exclusion criteria |
- Participants with nonplaque forms of psoriasis (for example, erythrodermic, guttate, or pustular) or with current drug-induced psoriasis (for example, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium) - Participants who have ever received guselkumab or adalimumab - History or current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances - Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (for example, compromise the well-being) of the participant or that could prevent, limit, or confound the protocol-specified assessments - Is pregnant, nursing, or planning a pregnancy (both men and women) within 5 months following the last administration of study drug |
Candidatos que tengan un tipo de psoriasis que no sea en placa (p. ej., eritrodérmica, en gota o pustulosa) o con psoriasis inducida por fármacos actual (por ejemplo, una nueva aparición de la psoriasis o una exacerbación de la psoriasis de bloqueadores beta, antagonistas del calcio o litio) - Los participantes que han recibido alguna vez guselkumab o adalimumab - Historia o actuales signos o síntomas de severa, progresiva,Tengan o hayan tenido signos o síntomas de alteraciones graves, progresivas o no controladas de tipo renal, cardíaco, vascular, pulmonar, gastrointestinal, endocrino, neurológico, hematológico, reumatológico, psiquiátrico o metabólico. Presenten un trastorno que haga que, en opinión del investigador, la participación en el estudio no sea la mejor opción para el paciente (por ejemplo, por comprometer su bienestar) o que pueda impedir, limitar o confundir las evaluaciones descritas en el protocolo- Está embarazada, amamantando o planea un embarazo (tanto hombres como mujeres) dentro de los 5 meses después de la última administración del fármaco del estudio |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The co-primary endpoints are the proportions of subjects who achieve an IGA score of cleared (0) or minimal (1) and the proportion of subjects who achieve a PASI 90 response at Week 16, comparing the guselkumab group and the placebo group. |
Los dos criterios de valoración principales son el porcentaje de pacientes que logran una puntuación IGA de aclaramiento (0) o enfermedad mínima (1) y el porcentaje de pacientes que obtienen una respuesta PASI 90 en la semana 16, comparando el grupo de guselkumab y el grupo de placebo. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
? The proportion of subjects who achieve an IGA score of cleared at Week 24, comparing the guselkumab group and the adalimumab group. ? The proportion of subjects who achieve an IGA score of cleared or minimal at Week 24, comparing the guselkumab group and the adalimumab group. ? The proportion of subjects who achieve a PASI 90 response at Week 24, comparing the guselkumab group and the adalimumab group. ? The time to loss of PASI 90 response through Week 48, comparing subjects randomized to placebo and subjects randomized to continue guselkumab 100 mg q8w at Week 28. ? The change from baseline in DLQI score at Week 16, comparing the guselkumab group and the placebo group. ? The proportion of subjects who achieve an IGA score of cleared or minimal at Week 16, comparing the guselkumab group and the adalimumab group. ? The proportion of subjects who achieve a PASI 90 response at Week 16, comparing the guselkumab group and the adalimumab group. ? The proportion of subjects who achieve a PASI 75 response at Week 16, comparing the guselkumab group and the adalimumab group. ? The proportion of subjects who achieve an ss-IGA score of absence of disease or very mild disease and have at least a 2-grade improvement from baseline at Week 16, comparing the guselkumab group and the placebo group among randomized subjects with scalp psoriasis and an ss-IGA score ?2 at baseline. ? The change from baseline in PSSD symptom score at Week 16, comparing the guselkumab group and the placebo group. ? The proportion of subjects who achieve a PSSD symptom score=0 at Week 24, comparing the guselkumab group and adalimumab group among randomized subjects with a baseline PSSD symptom score ?1.
Other Secondary Endpoints
Placebo Comparisons
? The proportion of subjects who achieve an IGA score of cleared and the proportion of subjects achieving an IGA score of mild or better (?2) at Week 16. ? The proportion of subjects who achieve a PASI 100 response, PASI 75 response, and a PASI 50 response at Week 16. ? The percent improvement from baseline in PASI response through Week 16. ? The proportion of subjects who achieve a DLQI score=0 or 1 at Week 16 among randomized subjects with baseline DLQI>1. ? The proportion of subjects with a reduction of 5 or more points in DLQI score at Week 16. ? The percent improvement from baseline in NAPSI at Week 16 among randomized subjects with nail psoriasis at baseline. ? The proportion of subjects who achieve an f-PGA score of clear or minimal and have at last 1 grade improvement from baseline at Week 16 among randomized subjects with f PGA ?2 at baseline. ? The proportion of subjects who achieve a PSSD symptom score=0 at Week 16 among randomized subjects with a baseline PSSD symptom score ?1. ? The proportion of subjects who achieve a PSSD sign score=0 at Week 16 among randomized subjects with a baseline PSSD sign score ?1. ? The change from baseline in individual scale score of PSSD components at Week 16 among randomized subjects. ? The proportion of subjects who achieve PSSD individual scale score of 0 at Week 16 among randomized subjects with scale score ?1 at baseline. ? The proportion of subjects who achieve an hf-PGA score of clear (0) or almost clear (1) and a reduction of at least 2 grades on the hf-PGA scale from baseline at Week 16 among randomized subjects with hand and/or foot psoriasis and an hf-PGA score ?2 at baseline. ? Change from baseline in the physical and mental component summary scores of SF-36 at Week 16. ? The change from baseline in HADS at Week 16. ? The change from baseline in WLQ at Week 16.
Guselkumab versus Adalimumab
? The proportion of subjects who achieve a PASI 75 response and a PASI 100 response at Week 24. ?The proportion of subjects who achieve an ss-IGA score of absence of disease or very mild disease and at least a 2-grade improvement from baseline at Week 24 among randomized subjects with scalp psoriasis and an ss-IGA score ?2 at baseline. ? The percent improvement from baseline in NAPSI at Week 24 among randomized subjects with nail psoriasis at baseline. ? The proportion of subjects who achieve an f-PGA score of clear or minimal and have at least a 1-grade improvement from baseline at Week 24 among subjects with f-PGA ?2 at baseline. ? The proportion of subjects who achieve an hf-PGA score of clear (0) or almost clear (1) and at least a 2-grade improvement from baseline at Week 24 among randomized subjects with hand and/or foot psoriasis and an hf-PGA score ?2 at baseline. ? The proportion of subjects who achieve a DLQI score=0 or 1 at Week 24 among randomized subjects with baseline DLQI>1. ? The change from baseline in the PSSD symptom score at Week 24.
Please see protocol for other secondary endpoints |
Comparación del porcentaje de pacientes que logran una puntuación IGA de aclaramiento (0) en la semana 24 entre el grupo de guselkumab y el grupo de adalimumab. Comparación del porcentaje de pacientes que logran una puntuación IGA de aclaramiento (0) o enfermedad mínima (1) en la semana 24 entre el grupo de guselkumab y el grupo de adalimumab. Comparación del porcentaje de pacientes que obtienen una respuesta PASI 90 en la semana 24 entre el grupo de guselkumab y el grupo de adalimumab. Comparación del tiempo transcurrido hasta la desaparición de la respuesta PASI 90 hasta la semana 48 entre los pacientes aleatorizados para recibir placebo y los aleatorizados para continuar con guselkumab 100 mg c8s en la semana 28. Comparación de la variación de la puntuación DLQI entre el momento basal y la semana 16 entre el grupo de guselkumab y el grupo de placebo. Análisis de no inferioridad del grupo de guselkumab respecto al grupo de adalimumab mediante el porcentaje de pacientes que logran una puntuación IGA de aclaramiento (0) o enfermedad mínima (1) en la semana 16. Análisis de no inferioridad del grupo de guselkumab respecto al grupo de adalimumab mediante el porcentaje de pacientes que obtienen una respuesta PASI 90 en la semana 16. Análisis de no inferioridad del grupo de guselkumab respecto al grupo de adalimumab mediante el porcentaje de pacientes que obtienen una respuesta PASI 75 en la semana 16. Análisis de superioridad del grupo de guselkumab respecto al grupo de adalimumab mediante el porcentaje de pacientes que logran una puntuación IGA de aclaramiento (0) o enfermedad mínima (1) en la semana 16. Análisis de superioridad del grupo de guselkumab respecto al grupo de adalimumab mediante el porcentaje de pacientes que obtienen una respuesta PASI 90 en la semana 16. Análisis de superioridad del grupo de guselkumab respecto al grupo de adalimumab mediante el porcentaje de pacientes que obtienen una respuesta PASI 75 en la semana 16. Comparación del porcentaje de pacientes que logran una puntuación ss-IGA de ausencia de enfermedad (0) o enfermedad muy leve (1) y presentan una mejora de al menos 2 grados entre el momento basal y la semana 16 entre el grupo de guselkumab y el grupo de placebo en los pacientes aleatorizados con psoriasis del cuero cabelludo y una puntuación ss-IGA mayor o igual a 2 en el momento basal. Comparación de la variación de la puntuación PSSD de los síntomas entre el momento basal y la semana 16 entre el grupo de guselkumab y el grupo de placebo. Comparación del porcentaje de pacientes que obtienen una puntuación PSSD de los síntomas igual a 0 en la semana 24 entre el grupo de guselkumab y el grupo de adalimumab, en los pacientes aleatorizados con una puntuación PSSD de los síntomas mayor o igual a 1 en el momento basal. Por favor ver Protocolo para otros Análisis secundarios. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 16/ Week 24/ Week 48 |
Semana 16/ Semana 24/ Semana 48 |
|
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 |
Germany |
Korea, Republic of |
Poland |
Russian Federation |
Spain |
United States |
|
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
|
LVLS |
Ultima visita del último paciente. |
|
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 | 8 |
E.8.9.1 | In the Member State concerned days | |
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 | 8 |