| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Giant Cell Arteritis |
| Arteritis de células gigantes |
|
| E.1.1.1 | Medical condition in easily understood language |
| Giant Cell Arteritis |
| Arteritis de células gigantes |
|
| 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 | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10018250 |
| E.1.2 | Term | Giant cell arteritis |
| E.1.2 | System Organ Class | 100000004866 |
|
| 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 sarilumab in patients with giant cell arteritis (GCA) as assessed by the proportion of patients with sustained remission for sarilumab compared to placebo, in combination with a corticosteroid (CS) tapering course. |
| Evaluar la eficacia de sarilumab en pacientes con arteritis de células gigantes (ACG) conforme a la proporción de pacientes con remisión prolongada para sarilumab en comparación con el placebo, en combinación con un ciclo de reducción gradual de corticoesteroides (CS). |
|
| E.2.2 | Secondary objectives of the trial |
-To demonstrate the efficacy of sarilumab in patients with GCA compared to placebo, in combination with CS taper with regards to:
-Clinical responses (such as responses based on disease remission rates, time to first disease flare) over time.
-Cumulative CS (including prednisone) exposure.
-To assess the safety (including immunogenicity) and tolerability of sarilumab in patients with GCA.
-To measure sarilumab serum concentrations in patients with GCA.
-To assess the effect of sarilumab on sparing glucocorticoid toxicity as measured by glucocorticoid toxicity index (GTI). |
- Demostrar la eficacia de sarilumab en pacientes con ACG en comparación con el placebo, en combinación con una reducción gradual de CS con respecto a:
1.Las respuestas clínicas (como las respuestas basadas en las tasas de remisión de la enfermedad, el tiempo hasta la primera exacerbación de la enfermedad) a lo largo del tiempo.
2. La exposición acumulada a CS (incluida la prednisona).
- Evaluar la seguridad (incluida la inmunogenia) y la tolerabilidad de sarilumab en pacientes con ACG.
- Medir las concentraciones séricas de sarilumab en pacientes con ACG.
- Evaluar el efecto de sarilumab sobre la preservación de la toxicidad de glucocorticoides conforme al índice de toxicidad de glucocorticoides (ITG). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
-Diagnosis of giant cell arteritis (GCA) according to European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria.
-New onset active disease or refractory active disease.
-At least one of the symptoms of GCA within 6 weeks of baseline.
-Either erythrocyte sedimentation rate (ESR) ≥30 mm/hour or C-reactive protein (CRP) ≥10 mg/L within 6 weeks of baseline.
-Receiving or able to receive prednisone 20-60 mg/day for the treatment of active GCA. |
Diagnóstico de la ACG clasificado de acuerdo con los siguientes criterios de la European League Against Rheumatism/American College of Rheumatology (EULAR/ACR)
Enfermedad activa de reciente aparición o enfermedad activa resistente al tratamiento
Al menos uno de los síntomas de la ACG 6 semanas antes del inicio
VSG de ≥30 mm/hora o PCR de ≥10 mg/l 6 semanas antes del inicio.
Recibir o poder recibir de 20 a 60 mg/día de prednisona para el tratamiento de la ACG activa. |
|
| E.4 | Principal exclusion criteria |
-Organ transplantation recipient (except corneas, unless it is within 3 months prior to baseline visit).
-Major ischemic event, unrelated to GCA, within 12 weeks of screening.
-Any prior use of the following therapies, for the treatment of GCA:
-Janus kinase inhibitor (e.g., tofacitinib) within 4 weeks of baseline.
-Cell-depletion agents (e.g., anti CD20) without evidence of recovery of B cells to baseline level.
-Abatacept within 8 weeks of baseline.
-Anakinra within 1 week of baseline.
-Tumor necrosis factor inhibitors within 2-8 weeks (etanercept within 2 weeks; infliximab, certolizumab, golimumab, or adalimumab within 8 weeks), or less than at least 5 half-lives have elapsed prior to baseline, whichever is longer.
-Therapeutic failure, including inadequate response or intolerance, or contraindication, to biological IL-6/(R) antagonist (prior experience with IL-6/(R) antagonist that was terminated for reasons unrelated to therapeutic failure at least 3 months before baseline is not exclusionary).
-Use of any alkylating agents including cyclophosphamide within 6 months of baseline.
-Use of immunosuppressant, such as hydroxychloroquine, cyclosporine, azathioprine,mycophenolate mofetil or leflunomide within 4 weeks of baseline. (Use of methotrexate (MTX) not exceeding 25 mg per week and have been stable for at least 3 months prior to baseline is not exclusionary).
-Concurrent use of systemic corticosteroids (CS) for conditions other than GCA.
-Use of IV CS at a dose equivalent to 100 mg of methylprednisolone or higher within 8 weeks of baseline for GCA therapy.
-Pregnant or breastfeeding woman.
-Patients with active or untreated latent tuberculosis.
-Patients with history of invasive opportunistic infections.
-Patients with fever associated with infection or chronic, persistent or recurring infections requiring active treatment.
-Patients with uncontrolled diabetes mellitus.
-Patients with non-healed or healing skin ulcers.
-Patients who received any live, attenuated vaccine within 3 months of baseline.
-Patients who are positive for hepatitis B, hepatitis C and/or HIV.
-Patients with a history of active or recurrent herpes zoster.
-Patients with a history of or prior articular or prosthetic joint infection.
-Prior or current history of malignancy.
-Patients who have had surgery within 4 weeks of screening or planned surgery during study.
-Patients with a history of inflammatory bowel disease or severe diverticulitis or previous gastrointestinal perforation. |
-Receptor de trasplante de órgano (excepto córneas, a menos que sea dentro de los 3 meses previos a la visita inicial).
-Evento isquémico mayor, sin relación con la ACG, dentro de las 12 semanas posteriores al cribado.
-Cualquier uso anterior de las siguientes terapias, para el tratamiento de ACG:
-Inhibidor de cinasa de Jano (por ejemplo, tofacitinib) dentro de las 4 semanas desde la basal.
- Agentes de reducción de la secreción celular (p. Ej., Anti CD20) sin evidencia de recuperación de las células B al nivel basal.
-Abatacept dentro de las 8 semanas desde la basal.
-Anakinra dentro de 1 semana desde la basal.
Los inhibidores del factor de necrosis tumoral en 2-8 semanas (etanercept en 2 semanas, infliximab, certolizumab, golimumab o adalimumab en 8 semanas) o menos de, como mínimo, 5 semividas anteriores al inicio; lo que suponga más tiempo.
- Fracaso terapéutico, incluida respuesta o intolerancia inadecuada, o contraindicación, al antagonista de IL-6 / (R) biológica (experiencia anterior con antagonista de IL-6 / (R) que se terminó por motivos no relacionados con el fallo terapéutico al menos 3 meses antes del inicio del estudio no es excluyente).
-Uso de cualquier agente alquilante, incluida la ciclofosfamida, dentro de los 6 meses desde la basal.
-Uso de inmunosupresores, como hidroxicloroquina, ciclosporina, azatioprina, micofenolato mofetilo o leflunomida dentro de las 4 semanas desde la basal. (El uso de metotrexato (MTX) que no exceda los 25 mg por semana y haya permanecido estable durante al menos 3 meses antes del inicio del estudio no es excluyente).
-Uso concurrente de corticosteroides sistémicos (CS) para afecciones distintas de la ACG.
-Uso de IV CS en una dosis equivalente a 100 mg de metilprednisolona o más alta dentro de las 8 semanas del inicio del tratamiento con ACG.
-Embarazada o mujer lactante.
- Pacientes con tuberculosis latente activa o no tratada.
- Pacientes con antecedentes de infecciones oportunistas invasivas.
- Pacientes con fiebre asociada a infección o infecciones crónicas, persistentes o recurrentes que requieren tratamiento activo.
- Pacientes con diabetes mellitus no controlada.
-Pacientes con úlceras cutáneas no cicatrizadas o curativas.
- Pacientes que recibieron cualquier vacuna atenuada en vivo dentro de los 3 meses desde la basal.
-Pacientes que son positivos para hepatitis B, hepatitis C y / o VIH.
- Pacientes con antecedentes de herpes zoster activo o recurrente.
- Pacientes con antecedentes de infección articular articular o protésica previa o antecedentes de esta.
- Pacientes que se han sometido a cirugía dentro de las 4 semanas posteriores a la detección o cirugía planeada durante el estudio.
- Pacientes con antecedentes de enfermedad inflamatoria intestinal o diverticulitis grave o perforación gastrointestinal previa. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of patients achieving sustained remission |
| Proporción de pacientes que logran la remisión sostenida |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Baseline to week 52 |
| Desde la basal hasta la semana 52 |
|
| E.5.2 | Secondary end point(s) |
1. Components of sustained remission (composite measure): Summary of the components of the sustained remission composite measure at Week 52
2. Cumulative corticosteroid dose: Total cumulative corticosteroid (including prednisone) dose over 52 weeks
3. Time to first GCA flare: Duration of first GCA flare from clinical remission up to Week 52
4. Change in glucocorticoid toxicity index: Changes from baseline in the glucocorticoid toxicity index and its components up to Week 52
5. Number of adverse events
6. Pharmacokinetic: Serum concentrations of sarilumab |
1. Componentes de la remisión sostenida (medida compuesta): Resumen de los componentes de la medida compuesta de remisión sostenida en la semana 52
2. Dosis acumulada de corticosteroides: dosis total acumulada de corticosteroides (incluida la prednisona) durante 52 semanas
3. Tiempo hasta el primer brote de ACG: Duración del primer brote de ACG desde la remisión clínica hasta la Semana 52
4. Cambio en el índice de toxicidad de los glucocorticoides: cambios desde el inicio en el índice de toxicidad de los glucocorticoides y sus componentes hasta la semana 52
5. Número de acontecimientos adversos
6. Farmacocinética: concentraciones séricas de sarilumab |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At Week 52
2. Up to Week 52
3. Up to Week 52
4. Up to Week 52
5. Up to Week 76
6. Up to Week 58 |
1. En la semana 52
2. Hasta la semana 52
3. Hasta la semana 52
4. Hasta la semana 52
5. Hasta la semana 76
6. Hasta la semana 58 |
|
| 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 | 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 | 4 |
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 64 |
| 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 |
| Australia |
| Austria |
| Belgium |
| Canada |
| Chile |
| Croatia |
| Denmark |
| Estonia |
| France |
| Germany |
| Hungary |
| Israel |
| Italy |
| Netherlands |
| Portugal |
| Russian Federation |
| Slovenia |
| Spain |
| Sweden |
| Switzerland |
| United Kingdom |
| United States |
|
| 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
|
| LVLS |
| Última 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 | 4 |
| 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 | 4 |
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