E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lupus Nephritis |
Nefritis Lúpica |
|
E.1.1.1 | Medical condition in easily understood language |
Lupus Nephritis |
Nefritis Lúpica |
|
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 | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025140 |
E.1.2 | Term | Lupus nephritis |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
|
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 |
The primary objective of the study is to evaluate the long-term safety and tolerability of BIIB023 in subjects with LN. |
El objetivo principal del estudio es evaluar la seguridad y la tolerabilidad a largo plazo de BIIB023 en sujetos con NL. |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives of this study are as follows:
-To evaluate the long-term efficacy of BIIB023 in subjects with LN - To evaluate the long-term immunogenicity of BIIB023 in subjects with LN
-To evaluate the long-term pharmacokinetics (PK) of BIIB023 in subjects with LN |
Los objetivos secundarios de este estudio son los siguientes:
? Evaluar la eficacia a largo plazo de BIIB023 en sujetos con NL.
? Evaluar la inmunogenicidad a largo plazo de BIIB023 en sujetos con NL.
? Evaluar la farmacocinética (FC) a largo plazo de BIIB023 en sujetos con NL. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible to participate in this study, candidates must meet the following eligibility criteria at Baseline (Day 1) or at the timepoint specified in the individual eligibility criterion listed:
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations.
2. Subjects who completed Week 52 of Study 211LE201 and did not discontinue BIIB023 or placebo study treatment.
3. Subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 6 months after their last dose of study treatment. |
Para ser elegibles para participar en este estudio, los candidatos deben cumplir los siguientes criterios de elegibilidad al inicio (día 1) o en el punto temporal especificado en el criterio de elegibilidad individual indicado:
1. Capacidad de comprender el objetivo y los riesgos del estudio y de dar el consentimiento informado firmado y fechado y la autorización para usar información sanitaria protegida de acuerdo con la normativa nacional y local sobre la privacidad de los sujetos.
2. Sujetos que completaron la semana 52 del estudio 211LE201 sin interrumpir el tratamiento del estudio con BIIB023 o con placebo.
3. Los sujetos en edad fértil deben tomar medidas anticonceptivas eficaces durante el estudio, así como estar dispuestos y ser capaces de continuar con estas durante los 6 meses posteriores a su última dosis del tratamiento del estudio. |
|
E.4 | Principal exclusion criteria |
Candidates will be excluded from study entry if any of the following exclusion criteria exist at Baseline (Day 1) or at the timepoint specified in the individual criterion listed:
1. Any significant change in medical history in subjects from Study 211LE201, including laboratory tests or current clinically significant condition that, in the opinion of the Investigator, would have excluded the subjects? participation. The Investigator must re-review the subject?s medical fitness for participation and consider any diseases that would preclude treatment under this protocol.
2. Subjects from Study 211LE201 who discontinued BIIB023 or placebo treatment prior to Week 52 of Study 211LE201.
3. Female subjects considering becoming pregnant while in the study, currently pregnant, or breast feeding.
4. Previous participation in Study 211LE202; subjects who were enrolled in Study 211LE202 and consequently withdrew for any reason are prohibited from re-entering the study.
5. Unwillingness or inability to comply with the requirements of the protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject?s ability to comply with the protocol.
6. Subjects who were prescribed MMF >3 g/day during Study 211LE201 and/or subjects for whom the Investigator is planning to prescribe MMF >3 g/day during this study.
7. Subjects having received disallowed concomitant medication during Study 211LE201 including the following:
a. Immunosuppressant used for therapy of LN (cyclophosphamide, nitrogen mustard, chlorambucil, vincristine, procarbazine, etoposide, mycophenolic acid, azathioprine, cyclosporine, methotrexate, atacicept, or any biologic B-cell-depleting therapy (e.g., anti-CD20 [rituximab], anti-CD22 [epratuzumab], or anti-BLyS/B-cell activating factor [e.g., belimumab] therapy).
b. Treatment with Campath (alemtuzumab)
c. Anti-tumor necrosis factor (infliximab, adalimumab, etanercept, efalizumab or alefacept) treatment
d. Cyclophosphamide, calcineurin, or a calcineurin inhibitor (i.e., cyclosporine A or tacrolimus)
8. Subjects with the following laboratory test results at Week 48 of Study 211LE201:
a. Absolute neutrophil count <1.5 × 1000/?L
b. Platelet count <20,000/?L; subjects with platelet count >20,000/?L and <150,000/?L who are experiencing, or at high risk for developing, clinically significant bleeding or organ dysfunction requiring therapy (as determined by the Investigator)
c. Hemoglobin <8.5 g/dL
d. Aspartate aminotransferase/serum glutamate oxaloacetate transaminase or alanine aminotransferase/serum glutamate pyruvate transaminase >2 × upper limit of normal established by the central laboratory
9. Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, makes the subject unsuitable for enrollment. |
Los candidatos serán excluidos del estudio si cumplen con alguno de los siguientes criterios de exclusión al inicio (día 1) o en el punto temporal especificado en el criterio individual indicado:
1. Cualquier cambio significativo en el historial médico de los sujetos del estudio 211LE201, incluidas las pruebas de laboratorio, o una afección actual clínicamente significativa que, en la opinión del investigador, habría excluido al sujeto de participar en el estudio. El investigador debe volver a revisar el estado médico del sujeto para poder participar y considerar cualquier enfermedad que pudiera impedir el tratamiento según este protocolo.
2. Los sujetos del estudio 211LE201 que interrumpieron el tratamiento con BIIB023 o placebo antes de la semana 52 del estudio 211LE201.
3. Sujetos del sexo femenino que se estén planteando quedarse embarazadas durante el estudio, que estén actualmente embarazadas o en periodo de lactancia.
4. Participación previa en el estudio 211LE202; los sujetos que estuvieron inscritos en el estudio 211LE202 y posteriormente se retiraron por cualquier motivo tienen prohibido volver a entrar en el estudio.
5. Falta de disposición o incapacidad por parte del sujeto de cumplir con los requisitos del protocolo, incluida la presencia de cualquier enfermedad (física, mental o social) que probablemente pueda afectar a la capacidad del sujeto de cumplir con el protocolo del estudio.
6. Sujetos a los que se recetó MMF > 3 g/día durante el estudio 211LE201 y/o sujetos a los que el investigador tiene planeado recetar MMF > 3 g/día durante este estudio.
7. Sujetos que han recibido medicación concomitante no permitida durante el estudio 211LE201, que incluye:
a. Inmunosupresores utilizados para el tratamiento de la NL (ciclofosfamida, mostaza nitrogenada, clorambucilo, vincristina, procarbazina, etopósido, ácido micofenólico, azatioprina, ciclosporina, metotrexato, atacicept), o cualquier tratamiento biológico que cause depleción de linfocitos B (p. ej., anti-CD20 [rituximab], anti-CD22 [epratuzumab], o tratamiento con anti-BLyS/factor de activación de linfocitos B [p. ej., belimumab]).
b. Tratamiento con Campath (alemtuzumab).
c. Tratamiento antifactor de necrosis tumoral (infliximab, adalimumab, etanercept, efalizumab o alefacept).
d. Ciclofosfamida, calcineurina, o inhibidor de la calcineurina (es decir, ciclosporina A o tacrolimus).
8. Sujetos con los siguientes resultados de las pruebas de laboratorio de la semana 48 del estudio 211LE201:
a. Recuento absoluto de neutrófilos < 1,5 × 103/?l.
b. Recuento plaquetario < 20.000/?l; sujetos con recuento plaquetario > 20.000/?l y < 150.000/?l que padecen o tienen un elevado riesgo de desarrollar hemorragia clínicamente significativa o disfunción orgánica que requiera tratamiento (según lo determinado por el investigador).
c. Hemoglobina < 8,5 g/dl.
d. Aspartato aminotransferasa/transaminasa glutámico-oxalacética sérica o alanina aminotransferasa/transaminasa glutámico-pirúvica sérica > 2 x límite superior de la normalidad establecido por el laboratorio central.
9. Otras razones no especificadas que, en opinión del investigador o de Biogen Idec, hagan que el sujeto no sea apto para la inscripción. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
-Incidence of adverse events (AEs) and serious adverse events (SAEs)
-Discontinuation of study treatment or withdrawal from the study due to an AE |
- Incidencia de acontecimiento adverso (AA) y acontecimiento advierso grave (AAG)
- Interrupcion del tratamiento o retirada del estudio debido a un acontecimiento adverso |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 108 and throughout the duration of study |
Semana 108 y a lo largo de la duración del estudio |
|
E.5.2 | Secondary end point(s) |
-Proportion of subjects who develop antibodies to BIIB023 -Incidence of partial renal response
-Incidence of complete renal response
-Time to complete renal response in subjects without complete renal response at baseline
-Duration of renal response
-Proportion of subjects who experience a new renal flare
-Time to renal flare
-Time to first non-renal systemic lupus erythematosus (SLE) flare
-Time to a major adverse renal event defined as the occurrence of one of the following:
a. New renal flare during the Dose-Blinded
-Treatment Period
a. Sustained doubling (present in 2 consecutive visits at least 4 weeks apart) of serum creatinine from Baseline (Day 1)
b. Initiation of rescue therapy for LN
c. End-stage renal disease
d. Death from any cause
-Changes in SLE index: Safety of Estrogens in Lupus Erythematosus-National Assessment Systemic Lupus Erythematosus Disease Activity Disease Activity Index (SELENA-SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR)
a. Steroid use
b. (Mycophenolate mofetil) MMF use
c. PK assessments |
? Proporción de sujetos que desarrollan anticuerpos de BIIB023.
? Incidencia de respuesta renal parcial.
? Incidencia de respuesta renal completa.
? Tiempo hasta completar la respuesta renal en sujetos sin respuesta renal completa al inicio.
? Duración de la respuesta renal.
? Proporción de sujetos que sufren una nueva exacerbación renal.
? Tiempo hasta la exacerbación renal.
? Tiempo hasta la primera exacerbación no renal de LES.
? Tiempo hasta un acontecimiento adverso renal importante definido como la ocurrencia de uno de los siguientes:
- Nueva exacerbación renal durante el periodo de tratamiento con enmascaramiento de la dosis.
- Duplicación sostenida (presente en 2 visitas consecutivas con un mínimo de 4 semanas de separación) de la creatinina sérica desde el inicio (día 1).
- Inicio del tratamiento de rescate para la NL.
- ERT.
- Muerte por cualquier causa.
? Cambios en el índice LES: Evaluación nacional de seguridad de los estrógenos en lupus eritematoso - Índice de actividad del lupus eritematoso sistémico (SELENA-SLEDAI) y Clínicas colaboradoras a nivel internacional en el lupus sistémico / Sociedad Estadounidense de Reumatología (SLICC/ACR).
? Uso de esteroides.
? Uso de MMF.
? Evaluaciones de FC. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 108 and/or throughout the duration of study |
Semana 108 y a lo largo de la duración del estudio |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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 | 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 |
Multicéntrico, en grupos paralelos, con enmascaramiento de la dosis y dos niveles posológicos |
Dose-Blinded, 2-Dose Level, Parallel-Group, Multicenter, Long-Term Extension Study |
|
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 |
Belgium |
Canada |
China |
France |
Italy |
Portugal |
Argentina |
Australia |
Brazil |
Colombia |
Germany |
Hong Kong |
Hungary |
Korea, Republic of |
Malaysia |
Spain |
Thailand |
Israel |
Mexico |
Peru |
Philippines |
Poland |
Russian Federation |
Serbia |
South Africa |
United States |
|
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
|
Last subject, last visit |
Ultimo paciente, Ultima visita |
|
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 | 11 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |