E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Lupus Erythematosus |
Lupus Eritematoso Sistemico |
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E.1.1.1 | Medical condition in easily understood language |
Lupus, an autoimmune disease |
Lupus, una enfermedad autoinmune |
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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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042945 |
E.1.2 | Term | Systemic lupus erythematosus |
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 characterise long-term safety and tolerability of intravenous anifrolumab. |
Caracterizar la tolerabilidad y la seguridad a largo plazo del anifrolumab por vía intravenosa |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects who have qualified for and received investigational product (anifrolumab or placebo) and completed the treatment period in Studies D3461C00004 or D3461C00005 (through Week 52) 2. Adequate peripheral venous access 3. Females with an intact cervix should have documentation of a Pap smear with no documented malignancy within 90 days before Day 1/Visit 1. Since access to a Pap smear may vary by country, the Sponsor recommends that local guidelines for obtaining Pap smears in subjects who have received immunomodulators or immunosuppressive treatment be followed. 4. Meets the following TB criteria: (a) Negative QuantiFERON®-TB Gold [QFT-G] test result for TB obtained from the study central laboratory at Week 52 of Studies D3461C00004 or D3461C00005; OR (b) Newly positive QFT-G test result for TB obtained at Week 52 of Studies D3461C00004 or D3461C00005 from the study central laboratory. A chest x-ray must be performed. If the chest x-ray shows no evidence of active TB, and the subject has no symptoms or medical history consistent with active TB, the subject must have a retest. If the retest is positive, the subject must initiate treatment for latent TB within 30 days of randomisation, but prior to the second dose of investigational product administration (Visit 2/Week 4); OR (c) Positive but not newly positive QFT-G test at Week 52 of Studies D3461C00004 or D3461C00005 from the study central laboratory. The subject must have been diagnosed with latent TB and must have documentation confirming completion of appropriate treatment OR initiate treatment for latent TB within 30 days of randomization, but prior to the second dose of investigational product administration (Visit 2/Week 4) (d) Newly indeterminate (confirmed on retest) or indeterminate but not newly indeterminate QFT-G test result at Week 52 of Studies D3461C00004 or D3461C00005 from the study central laboratory with ongoing QFT-G testing for TB according to the Study Plan 5. In the opinion of the Investigator, subject must be able to comprehend the ICF and all protocol related assessments |
1.Pacientes aptos que hayan recibido el producto en investigación (anifrolumab o placebo) y que hayan terminado el periodo de tratamiento en los estudios D3461C00004 o D3461C00005 (hasta la semana 52) 2.Acceso venoso periférico adecuado 3.Las mujeres con cuello uterino intacto deben documentar que carecen de neoplasias malignas mediante una prueba de Papanicoláu realizada dentro de los 90 días anteriores al día 1/visita 1. Dado que el acceso a la prueba de Papanicoláu puede variar de un país a otro, el promotor recomienda seguir las directrices locales para su realización en pacientes receptoras de inmunomoduladores o de tratamiento inmunodepresor. 4.Cumplimiento de los criterios de TB (tuberculosis) siguientes: a)Resultado negativo en la prueba QuantiFERON®-TB Gold (QFT-G) de la TB obtenido del laboratorio central del estudio en la semana 52 de los estudios D3461C00004 o D3461C00005 O b)Resultado positivo de nueva aparición en la prueba QFT-G de la TB obtenido del laboratorio central del estudio en la semana 52 de los estudios D3461C00004 o D3461C00005. Debe realizarse una radiografía de tórax. Si la radiografía de tórax no muestra indicios de TB activa y el paciente carece de síntomas o de antecedentes médicos compatibles con TB activa, se deberá repetir la prueba al paciente. Si la repetición da positivo, el paciente debe comenzar un tratamiento para la TB latente en los 30 días siguientes a la aleatorización, pero antes de administrar la segunda dosis del producto en investigación (visita 2/semana 4). O c)Resultado positivo, pero no de nueva aparición en la prueba QFT-G obtenido del laboratorio central del estudio en la semana 52 de los estudios D3461C00004 o D3461C00005. Se debe haber diagnosticado al paciente TB latente y debe tener documentación que confirme la realización completa del tratamiento correspondiente O comenzar un tratamiento para la TB latente en los 30 días siguientes a la aleatorización, pero antes de administrar la segunda dosis del producto en investigación (visita 2/semana 4)Resultado indeterminado de nueva aparición (confirmado al repetir la prueba) o no en la prueba QFT-G obtenido del laboratorio central del estudio en la semana 52 de los estudios D3461C00004 o D3461C00005 con pruebas continuas de QFT-G para la TB según el plan del estudio 5.En opinión del investigador, el paciente debe ser capaz de comprender el FCI y todas las evaluaciones relacionadas con el protocolo |
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E.4 | Principal exclusion criteria |
1. Receipt of any of the following within the last 60 days: (a) Azathioprine >200 mg/day (b) Mycophenolate mofetil/mycophenolic acid >2.0 g/day (c) Oral, subcutaneous, or intramuscular methotrexate >25 mg/week (d) Mizoribine >150 mg/day 2. Receipt of any investigational product (small molecule or biologic agent other than anifrolumab) within 4 weeks or 5 half-lives prior to Day 1/Visit 1, whichever is greater 3. Receipt of any of the following: (a) Any live or attenuated vaccine within 8 weeks prior to Day 1/Visit 1 (administration of killed vaccines is acceptable, the Sponsor recommends Investigators ensure all subjects are up to date on required vaccinations, including influenza [inactivated/recombinant] vaccine prior to study entry) (b) Bacillus Calmette-Guerin (BCG) vaccine between the end of Studies D3461C00004 or D3461C00005 and Day 1/Visit 1 4. Active severe SLE-driven renal or neuropsychiatric disease 5. Any underlying condition that predisposes the subject to infection, including history of/current human immunodeficiency virus (HIV) infection 6. Subjects with Hepatitis B core antibody (HBcAb) positivity at enrolment of Studies D3461C00004 or D3461C00005 will be tested every 3 months for Hepatitis B virus (HBV) DNA. To remain eligible in the LTE study, subject HBV DNA levels must remain below the lower limit of quantitation as per the central laboratory. 7. Opportunistic infection requiring hospitalisation or parenteral antimicrobial treatment within 3 years of Day 1/Visit 1 |
Recepción de cualquiera de los medicamentos siguientes durante los 60 días previos al día 1/visita 1: (a)Azatioprina >200 mg/día (b)Micofenolato mofetilo/ácido micofenólico >2,0 g/día (c)Metotrexato por vía oral, subcutánea o intramuscular >25 mg/semana (d)Mizoribina >150 mg/día 2.Recepción de cualquier producto en investigación (agente tradicional o biológico distinto del anifrolumab) durante las 4 semanas o las 5 semividas previas al día 1/visita 1, aplicando el plazo que sea más largo 3.Recepcion de cualquiera de los siguientes: a)Cualquier vacuna de microorganismos vivos o atenuados dentro de las 8 semanas anteriores al día 1/visita 1 (se permite la administración de vacunas muertas; el promotor recomienda a los investigadores que se aseguren de que todos los pacientes hayan recibido todas las vacunas necesarias, incluida la de la gripe [inactivada/recombinante] antes de ingresar en el estudio) b)Vacuna contra el bacilo de Calmette-Guérin (BCG) entre el final de los estudios D3461C00004 o D3461C00005 y el día 1/visita 1 4.Enfermedad renal o neuropsiquiátrica grave activa causada por el LES 5.Cualquier afección subyacente que predisponga al paciente a infecciones, como infección previa o en curso por el virus de la inmunodeficiencia humana (VIH) 6.A los pacientes que den positivo para anticuerpos contra el antígeno central del virus de la hepatitis B (HBcAb) en el momento de la inclusión en los estudios D3461C00004 o D3461C00005 se les realizará cada 3 meses la prueba de ADN del virus de la hepatitis B (VHB). Para seguir siendo apto para el estudio de ELP, los niveles de ADN del VHB del paciente deben permanecer por debajo del límite mínimo de cuantificación (LMC) según el laboratorio central 7.Infección oportunista que haya requerido hospitalización o tratamiento antimicrobiano parenteral durante los 3 años anteriores al día 1/visita 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Rates of adverse events of special interest and serious adverse events from baseline of the Phase 3 pivotal Studies D3461C00004 or D3461C00005 |
Indice de efectos adversos de especial interés y efectos adversos graves tomando como referencia los estudios pivotales D3461C00004 o D3461C00005 |
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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) |
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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 | 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 | 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) | 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 | No |
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 | 2 |
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 | 71 |
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 |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
Colombia |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Lithuania |
Mexico |
New Zealand |
Peru |
Poland |
Romania |
Russian Federation |
Singapore |
South Africa |
Spain |
Taiwan |
Ukraine |
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
|
LVLS |
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 | 5 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |