E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid Arthritis |
Artritis reumatoide |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis |
Artritis reumatoide |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective 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 assess, in the same study, the safety of sarilumab and tocilizumab in patients with rheumatoid arthritis (RA) who are inadequate responders to or intolerant of tumor necrosis factor (TNF) antagonists. |
Evaluar, en el mismo estudio, la seguridad de sarilumab y tocilizumab en pacientes con artritis reumatoide (AR) con respuesta inadecuada o con intolerancia de los antagonistas del factor de necrosis tumoral (TNF). |
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E.2.2 | Secondary objectives of the trial |
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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 |
To collect DNA and other biomarkers for future use for the purpose of discovery of predictive biomarkers. Version 1 20 November 2012 |
Recoger ADN y otros biomarcadores para utilizarlos en el futuro con el fin de descubrir biomarcadores predictivos. Version 1, 20/11/2012 |
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E.3 | Principal inclusion criteria |
Diagnosis of RA, according to the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) 2010 Rheumatoid Arthritis Classification Criteria with ? 3 months disease duration. ACR Class I-III functional status, based on the 1991 revised criteria. Moderate-to-severely active RA. Anti-TNF therapy failures, defined as patients with an inadequate clinical response defined by the investigator, after being treated for at least 3 consecutive months, and/or intolerance to at least 1 anti-TNF blocker(s), resulting in or requiring their discontinuation. TNF-blockers may include, but are not limited to, etanercept, infliximab, adalimumab, golimumab and/or certolizumab pegol. Continuous treatment with one or a combination of non-biologic disease modifying antirheumatic drugs (DMARDs) for at least 12 consecutive weeks and on a stable dose(s) for at least 6 consecutive weeks prior to randomization: - Methotrexate ? 10 to 25 mg/wk orally or intra muscular (or per local labeling requirements if the dose range differs) - Leflunomide ? 10 to 20 mg orally daily - Sulfasalazine (SSZ) ? 1000 to 3000 mg orally daily - Hydroxychloroquine (HCQ) ? 200 to 400 mg orally daily |
Diagnóstico de AR, según los Criterios de clasificación de la artritis reumatoide del American College of Rheumatology (ACR ) / Liga Europea contra el Reumatismo (EULAR) 2010 con ? 3 meses de duración de la enfermedad (1) Estado funcional de clase I-III de ACR, según los criterios revisados de 1991 (2) El tratamiento continuo con un FARME no biológico o una combinación de estos (excepto el uso combinado de leflunomida [LEF] y metotrexato [MTX]) durante al menos 12 semanas consecutivas y a dosis estable(s) durante al menos 6 semanas consecutivas antes de la selección: - Metotrexato (MTX) ? 10 a 25 mg/semana (o según los requisitos de la ficha técnica local si el intervalo de dosis difiere) - Leflunomida (LEF) ? 10 a 20 mg al día - Sulfasalazina (SSZ) - 1.000 en 3.000 mg al día - Hidroxicloroquina (HCQ) - 200 a 400 mg al día La enfermedad activa se define como: - al menos 4 de 66 articulaciones inflamadas y 4 de 68 articulaciones dolorosas con la palpación - proteína C reactiva de alta sensibilidad (PCRas) ? 4 mg/l Los pacientes que según la evaluación del investigador hayan tenido una respuesta inadecuada a al menos un antagonista del TNF, después de haber sido tratados durante al menos 3 meses consecutivos, en cualquier momento antes de la aleatorización o pacientes que no hayan tolerado al menos 1 antagonista del TNF, que provoque la suspensión del tratamiento. Los antagonistas del TNF pueden ser etanercept, infliximab, adalimumab, golimumab o certolizumab pegol. Los pacientes deben haber firmado un consentimiento informado por escrito antes de realizar cualquier procedimiento relacionado con el estudio. |
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E.4 | Principal exclusion criteria |
Patients <18 years of age. Use of parenteral corticosteroids or intra-articular corticosteroids within 4 weeks prior to screening. Use of oral corticosteroids in a dose higher than prednisone 10 mg or equivalent per day, or a change in dosage within 4 weeks prior to screening. Past history of, or current, autoimmune or inflammatory systemic or localized joint disease(s) other than RA. History of juvenile idiopathic arthritis or arthritis onset prior to age 16. Severe systemic RA, including but not limited to vasculitis, pulmonary fibrosis, and/or Felty?s syndrome. Participation in any clinical research study that evaluated an investigational drug or therapy within 5 half-lives or 60 days of the Screening Visit, whichever is longer. Patients with active tuberculosis or latent tuberculosis infection. Prior or current history of interstitial lung disease. Prior treatment with anti-IL-6 or anti-IL-6R antagonist therapies, including but not limited to tocilizumab or sarilumab. Treatment with anti-TNF agents, as follows: ? Etanercept: within 28 days prior to randomization ? Infliximab, adalimumab, golimumab, certolizumab pegol: within 42 days prior to randomization. Treatment with RA-directed biologic agents with non- TNF-? antagonist mechanisms without adequate washout as follows: ? Anakinra: within 28 days prior to randomization ? Abatacept: within 42 days prior to randomization ? Rituximab or other cell depleting agent: Within 6 months prior to randomization or until total lymphocyte count and CD 19+ lymphocyte count are normalized, or whichever is longer. Prior treatment with a janus kinase (JAK) inhibitor (eg, tofacitinib). Patients with a history of invasive opportunistic infection. Prior or current history of malignancy, including lymphoproliferative diseases, other than adequately-treated carcinoma in-situ of the cervix, nonmetastatic squamous cell or basal cell carcinoma of the skin, within 5 years prior to the randomization (baseline) visit. Prior or current history of other significant concomitant illness(es) that, according to Investigator?s judgment, would adversely affect the patient?s participation in the study. |
Edad < 18 años Uso de corticoesteroides por vía parenteral o intraarticular en las 4 semanas previas a la selección Uso de corticoides orales a una dosis superior a prednisona 10 mg o equivalente al día, o una variación de la dosis en las 4 semanas previas a la selección El tratamiento previo con terapias de antiinterleucina-6 (anti-IL-6) o antagonistas del receptor antiinterleucina-6 (IL-6R), incluidos, entre otros, tocilizumab o sarilumab El tratamiento con los siguientes antagonistas del TNF: - Etanercept: en los 28 días previos a la visita de aleatorización - Infliximab, adalimumab, golimumab y certolizumab pegol: en los 42 días previos a la aleatorización Tratamiento con fármacos biológicos para la AR distintos a los antagonistas del TNF-? como: - Anakinra: en los 28 días previos a la aleatorización - Abatacept: en los 42 días previos a la aleatorización - Rituximab u otros fármacos que provoca la destrucción de células: en los 6 meses previos a la aleatorización o hasta que el recuento de linfocitos totales y el recuento de linfocitos CD19 + se haya normalizado, lo que sea más largo Tratamiento previo con un inhibidor de kinasa de Janus (JAK). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety as measured by adverse events/serious adverse events, physical examinations, clinical laboratory, ECGs. |
Seguridad medida por los acontecimientos adversos/acontecimientos adversos graves, exploración física, valores analíticos y los parámetros electrocardiográficos (ECG). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 24 weeks |
Hasta las 24 semanas |
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E.5.2 | Secondary end point(s) |
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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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Doble enmascarado |
Double-dummy |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 |
Belgium |
Brazil |
Colombia |
Czech Republic |
Estonia |
Finland |
Germany |
Hungary |
Israel |
Italy |
Mexico |
Netherlands |
Norway |
Poland |
Romania |
Russian Federation |
Spain |
Sweden |
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 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |