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] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess by PET/CT the effect of Sarilumab in the carotid atheroma plaque (effect on the inflammatory component as well as on mineralization) in patients with rheumatoid arthritis over 6 months of Sarilumab treatment. |
Evaluar por PET/CT el efecto de Sarilumab sobre la placa de ateroma carotídea (efecto sobre el componente inflamatorio y la mineralización) en pacientes con AR tratados durante 6 meses con Sarilumab. |
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E.2.2 | Secondary objectives of the trial |
-To determine the change in 18F-FDG PET/CT uptake at the aortic wall (inflammatory component) over 6 months of Sarilumab treatment. - To assess the change in 18F-FNa PET/CT uptake at the aortic wall (mineralization) over 6 months of Sarilumab treatment. -To analyze the correlation with clinical improvement of the disease, by using well-defined methods to determine disease activity in RA (including DAS28, CDAI, SDAI, erythrocyte sedimentation rate (ESR), CRP) over 6 months of Sarilumab treatment. -To evaluate the change in adipokines, biomarkers of endothelial cell activation and inflammation, as well as biomarkers related to metabolic syndrome (MetS) over 6 months of Sarilumab treatment. |
- Determinar el cambio en la captación de 18F-FDG de la PET/CT en la pared aórtica (componente inflamatorio) tras 6 meses de tratamiento con Sarilumab. - Evaluar el cambio en la captación de 18F-FNa de la PET/CT en la pared aórtica (mineralización) tras 6 meses de tratamiento con Sarilumab. - Analizar la correlación con la mejoría clínica de la enfermedad, utilizando métodos para determinar la actividad de la enfermedad (entre ellos DAS28, CDAI, SDAI, velocidad de sedimentación globular (VSG), proteína C reactiva (PCR) tras 6 meses de tratamiento con Sarilumab. - Estudiar los cambios en adipocinas, biomarcadores de activación endotelial e inflamación, así como biomarcadores asociados a síndrome metabólico (SM), tras 6 meses de tratamiento con Sarilumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients ≥ 18 years diagnosed with active RA: DAS28>3.2 and levels of CRP of at least 1 mg/dl. - Naïve to biologic DMARDs (bDMARDs) or refractory to a single bDMARD different from anti- IL-6 agents. - Only patients with plaques assessed by carotid US will be included in the PET/CT study. Plaques will be detected by US (for this purpose of at least 1.5 mm). - Patients who are candidates for sarilumab according to summary of product characteristics (SmPC). - Patients must sign informed consent. |
-Edad ≥18 años con AR activa: DAS28>3.2 y niveles de PCR ≥1 mg/dL. - Naïve a DMARDs biológicos o refractarios a un único biológico diferente a los fármacos anti-IL-6. - Sólo se realizará el PET/CT a los pacientes que presentan placas, detectadas por ecografía de carótida (de al menos 1.5 mm). - Pacientes que sean candidatos para el sarilumab de acuerdo con el resumen de las características del producto. - Pacientes que firmen el consentimiento informado. |
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E.4 | Principal exclusion criteria |
- Patients with previous history of CV events. - Patients with history of diabetes or chronic renal failure. - Patients with an absolute neutrophil count (ANC) less than 2 x 109/L. - Patients with platelet count below 150 x 103/μL. - Patients with elevated transaminases, ALT or AST greater than 1.5 x ULN. - Patients with an active infection, including localized infections. - Patients who are not candidates for sarilumab according to SmPC. - Patients enrolled in other clinical trial or research project. - Patients who do not sign the informed consent. -Women who are pregnant or breastfeeding, or those of child-bearing who are not using an effective method of contraception |
-Historia previa de eventos CV. -Historia de diabetes o fallo renal crónico. - Recuento absoluto de neutrófilos <2 x109/L. - Recuento de plaquetas <150 x 103/μL. -Transaminasas elevadas (ALT o AST > 1,5 x LSN). - Infección activa, incluyendo infecciones localizadas. - Que tengan contraindicada la administración de Sarilumab. - Pacientes que estén participando en otro ensayo clínico o proyecto de investigación. - Negativa a participar en el estudio y a firmar el consentimiento. - Mujeres embarazadas o en periodo de lactancia, o aquellas mujeres en edad fértil que no empleen algún método anticonceptivo eficaz |
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E.5 End points |
E.5.1 | Primary end point(s) |
Effect of Sarilumab over 6 months of treatment, in the carotid atheroma plaque (effect on the inflammatory component as well as on mineralization) evaluated by PET/CT in patients diagnosed with RA. |
Efecto de Sarilumab en un período de 6 meses de tratamiento, sobre la placa de ateroma carotídea (efecto sobre el componente inflamatorio y la mineralización) en pacientes con AR evaluado por PET/CT . |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
BASAL AND 6 MONTHS |
BASAL Y 6 MESES |
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E.5.2 | Secondary end point(s) |
- Change in 18F-fluorodeoxyglucose (18F-FDG) PET/CT uptake at the aortic wall (inflammatory component) over 6 months of treatment with Sarilumab. - Change in 18F-sodium fluoride (18F-NaF) PET/CT uptake at the aortic wall (mineralization) over 6 months of treatment with Sarilumab. - Clinical improvement of the disease after onset of treatment with Sarilumab measured by disease activity score (DAS)28, clinical disease activity index (CDAI), simple disease activity index (SDAI) and routine laboratory measures of inflammation, as C-reactive protein (CRP) levels. - Reduction of insulin resistance (IR) and improvement of insulin sensitivity, modulation of lipid profile and changes in mRNA expression and serum levels of adipokines, metabolic syndrome (MetS)-related biomarkers and endothelial cell activation and inflammation biomarkers. |
- Cambio en la captación de 18F-FDG de la PET/CT en la pared aórtica (componente inflamatorio) tras 6 meses de tratamiento con Sarilumab. - Cambio en la captación de 18F-FNa de la PET/CT en la pared aórtica (mineralización) tras 6 meses de tratamiento con Sarilumab. - Mejoría clínica de la enfermedad tras el inicio del tratamiento con Sarilumab, utilizando métodos para determinar la actividad de la enfermedad (entre ellos DAS28, CDAI, SDAI, y parámetros inflamatorios de rutina, como los niveles de proteína C reactiva (PCR). - Reducción de resistencia insulínica y mejora de la sensibilidad insulínica, modulación del perfil lipídico y cambios en la expresión de ARNm y niveles séricos de adipocinas, biomarcadores asociados a SM y biomarcadores de activación endotelial e inflamación. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
BASAL, 3 AND 6 MONTHS |
BASAL, 3 Y 6 MESES |
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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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Ensayo clínico no aleatorizado con medicamentos |
Non-randomised clinical trial with drugs |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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LPLV: last patient last visit |
LPLV: ultima visita del ultimo 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 | |
E.8.9.1 | In the Member State concerned months | 26 |
E.8.9.1 | In the Member State concerned days | |