E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Psoriatic Arthritis |
Artritis psoriásica |
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E.1.1.1 | Medical condition in easily understood language |
Psoriatic Arthritis |
Artritis psoriásica |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037160 |
E.1.2 | Term | Psoriatic arthritis |
E.1.2 | System Organ Class | 100000004859 |
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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 demonstrate that the efficacy of secukinumab 150 mg s.c. (with or without loading regimen) or 300 mg s.c. with loading regimen, at Week 24 is superior to placebo based on proportion of subjects achieving American College of Rheumatology 20 (ACR20) response in subjects with active PsA. |
Demostrar que la eficacia de secukinumab 150 mg s.c. (con o sin régimen de carga) o 300 mg s.c. con régimen de carga, en la Semana 24 es superior al placebo en base a la proporción de pacientes que alcancen una respuesta de 20 (ACR20) según la American College of Rheumatology en pacientes con APs activa. |
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E.2.2 | Secondary objectives of the trial |
W24,AIN=secukinumab -Efficacy AIN150mg(w/ or w/o loading)or 300mg(w/ loading),compared w/pbo based on proportion of subjects achieving ACR50 -Change from BSL with AIN150mg(w/ or w/o loading)or 300mg(w/ loading) compared w/pbo for joint/bone structural damage -Improvement on AIN150mg(w/ or w/o loading)or 300mg(w/ loading),compared w/pbo for changes in HAQ-DI relative to BSL -Efficacy AIN pooled regimen(w/ or w/o loading,300mg w/ loading) compared w/pbo based on proportion of subjects w/ dactylitis or enthesitis in the subset of subjects who have dactylitis or enthesitis at BSL -Efficacy AIN150mg(w/ or w/o loading),or 300mg(w/ loading) compared w/pbo based on proportion of subjects achieving PASI75 -Improvement on AIN150mg(w/ or w/o loading)or 300mg(w/ loading) compared w/pbo relative to BSL for ?changes in DAS28-CRP(hsCRP) ?SF-36-PCS -Efficacy AIN150mg(w/ or w/o loading),or 300mg(w/ loading) compared w/pbo based on proportion of subjects achieving PASI90 -Safety/tolerability |
en semana 24, AIN= secukinumab con=C sin=s placebo=pbo eficacia de AIN 150 mg (c/s régimen de carga), o 300 mg (c/s régimen de carga), comparado con pbo en base a la proporción de pacientes que alcancen una respuesta ACR50. cambio respecto a la visita basal con AIN 150 mg (c/s régimen de carga), o 300 mg (c/s régimen de carga), comparado con pbo en cuanto al daño estructural articular/óseo mTSS). Mejoría con AIN 150 mg (c/s régimen de carga), o 300 mg (c/s régimen de carga), comparado con pbo en cuanto a la actividad de la enfermedad evaluada por los cambios en HAQ-DI© respecto a la visita basal. eficacia combinado AIN 150 mg (c/s régimen de carga), o 300 mg (c/s régimen de carga), comparado con pbo en base a la proporción de pacientes con dactilitis o entesitis en el subgrupo de pacientes que presenten dactilitis o entesitis en la BSL. eficacia AIN 150 mg (c/s régimen de carga) o 300 mg (c/s régimen de carga)con placebo en base a la proporción de pacientes que alcancen PASI75 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months with moderate to severe PsA who must have at BSL ?3 tender joints out of 78 and ?3 swollen joints out of 76 (dactylitis of a digit counts as one joint each). -Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies negative at screening. -Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis or a documented history of plaque psoriasis. -Subjects with PsA should have taken NSAIDs for at least 4 weeks prior to randomization with inadequate control of symptoms or at least one dose if stopped due to intolerance to NSAIDs. -Subjects who are regularly taking NSAIDs as part of their PsA therapy are required to be on a stable dose for at least 2 weeks before study randomization and should remain on a stable dose up to Week 24. -Subjects taking corticosteroids must be on a stable dose of ?10 mg/day prednisone or equivalent for at least 2 weeks before randomization and should remain on a stable dose up to Week 24. -Subjects taking MTX ?25 mg/week) are allowed to continue their medication if the dose is stable for at least 4 weeks before randomization and should remain on a stable dose up to Week 52. -Subjects on MTX must be on folic acid supplementation at randomization. -Subjects who are on a DMARD other than MTX must discontinue the DMARD 4 weeks prior to randomization visit except for leflunomide, which has to be discontinued for 8 weeks prior to randomization unless a cholestyramine wash-out has been performed. -Subjects who have been on a TNF? inhibitor must have experienced an inadequate response to previous or current treatment with a TNF? inhibitor given at an approved dose for at least 3 months or have stopped treatment due to safety/tolerability problems after at least one administration of a TNF?inhibitor. -Subjects who have previously been treated with TNF?inhibitors (investigational or approved) will be allowed entry into study after appropriate wash-out period prior to randomization. -Other protocol-defined inclusion criteria may apply. |
Diagnóstico de APs clasificada según los criterios para la clasificación de la Artritis Psoriásica (CASPAR) y con síntomas durante al menos 6 meses con APs moderada a grave, que en la visita basal deberán tener ?3 articulaciones dolorosas de 78 y ?3 articulaciones tumefactas de 76 (la dactilitis de un dedo cuenta como una articulación cada una). Factor reumatoide (FR) y anticuerpos contra el péptido cíclico de la citrulina (anti-CCP) negativos en la selección Diagnóstico de psoriasis en placas activa o cambios en las uñas que coincidan con la psoriasis o antecedentes documentados de psoriasis en placas. Los pacientes con APs deberían haber tomado AINEs durante al menos 4 semanas antes de la aleatorización con control inadecuado de los síntomas o al menos una dosis si se interrumpe debido a intolerancia a los AINEs Los pacientes que estén tomando regularmente AINEs como parte de su terapia contra la APs será necesario que tomen una dosis estable durante al menos 2 semanas antes de la aleatorización en el estudio y deberían permanecer con una dosis estable hasta la Semana 24. Los pacientes que tomen corticoesteroides deberán estar con una dosis estable de ? 10 mg/día de prednisona o equivalente durante al menos 2 semanas antes de la aleatorización y deberían permanecer con una dosis estable hasta la Semana 24 A los pacientes que tomen MTX (? 25 mg/semana) se les permite continuar con su medicación si la dosis es estable durante al menos 4 semanas antes de la aleatorización y deberían permanecer con una dosis estable hasta la Semana 52. -Los pacientes que tomen MTX deberán tomar suplemento de ácido fólico en la aleatorización -A los pacientes que estén tomando un FAME distinto a MTX se les deberá retirar el FAME 4 semanas antes de la visita de aleatorización, excepto en el caso de leflunomida, la cual habrá de interrumpirse durante 8 semanas antes de la aleatorización, salvo que se haya realizado un lavado de colestiramina. Los pacientes que hayan estado tomando un inhibidor de TNF? deberán haber tenido una respuesta inadecuada al tratamiento previo o actual con un inhibidor de TNF? administrado a una dosis aprobada durante al menos 3 meses o haber interrumpido el tratamiento debido a problemas de seguridad/tolerabilidad tras al menos una administración de un inhibidor de TNF? A los pacientes que previamente hayan sido tratados con inhibidores de TNF? (en investigación o aprobados) se les permitirá ser incluidos en el estudio después de un período de lavado apropiado antes de la aleatorización: a. 4 semanas para Enbrel® (etanercept) -con una semivida terminal de 102 ± 30 horas (vía s.c.). b. 8 semanas o más para Remicade® (infliximab) - con una semivida terminal de 8,0-9,5 días (infusión i.v.). c. 10 semanas o más para Humira® (adalimumab) - con una semivida terminal de 10-20 días (2 semanas en promedio) (vía s.c.). |
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E.4 | Principal exclusion criteria |
-Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process. -Subjects taking high potency opioid analgesics. -Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor. -Ongoing use of prohibited psoriasis treatments / medications (e.g., topical corticosteroids, UV therapy) at randomization. -Any intramuscular or intravenous or intra-articular corticosteroid treatment within 4 weeks before randomization. -Subjects who have ever received biologic immunomodulating agents except for those targeting TNF? (investigational or approved). -Previous treatment with any cell-depleting therapies including but not limited to anti- CD20, investigational agents -Other protocol-defined exclusion criteria may apply. |
Radiografía de tórax o resonancia magnética (RM) de tórax con evidencia de proceso infeccioso o maligno en curso, obtenida en los 3 meses previos a la selección y evaluada por un médico cualificado. Pacientes que tomen analgésicos opioides de alta potencia (p. ej., metadona, hidromorfona, morfina). Exposición previa a secukinumab o a otro biofármaco que se dirija directamente a IL-17 o al receptor de IL-17. Uso actual de tratamientos / medicaciones antipsoriásicas prohibidas (p. ej., corticoesteroides tópicos, terapia con UV) en la aleatorización. Pacientes que alguna vez hayan recibido inmunomoduladores biológicos, excepto los que se dirijan a TNF? (en investigación o aprobados) Tratamiento previo con cualquier terapia de eliminación de linfocitos, incluidas pero no limitadas a anti-CD20, fármacos en investigación (p. ej., CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19). |
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E.5 End points |
E.5.1 | Primary end point(s) |
American College of Rheumatology 20 (ACR20) response |
Repuesta American College of Rheumatology 20 (ACR20) |
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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) |
-American College of Rheumatology 50 (ACR50) response -Van der Heijde modified total Sharp score -Health assessment questionnaire disability index© (HAQ-DI©) score -Dactylitis -Enthesitis -Psoriasis Area and Severity Index 75 (PASI75) response -Disease Activity Score for 28 joints (DAS28-CRP) -Short Form 36 Health Survey (SF36) physical component score -Psoriasis Area and Severity Index 90 (PASI90) |
American College of Rheumatology 50 (ACR50) -resultado Van der Heijde mTSS re -resultado de HAQ-DI©, SF36 -Dactilitis -entesitis -PASI75, PASI 90 -DAS28-CRP |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 116 |
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 |
Brazil |
Canada |
Chile |
Czech Republic |
Denmark |
Egypt |
Estonia |
Finland |
Germany |
Greece |
Guatemala |
Hungary |
India |
Ireland |
Israel |
Italy |
Latvia |
Lithuania |
Mexico |
Netherlands |
Philippines |
Russian Federation |
Serbia |
Spain |
Sweden |
Thailand |
United Kingdom |
United States |
Vietnam |
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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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LVLS |
Última visita del último paciente |
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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 | 10 |
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 | 10 |