E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid Arthritis (RA) |
Artritis reumatoide (AR) |
|
E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis (RA) |
Artritis reumatoide (AR) |
|
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 | 18.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021428 |
E.1.2 | Term | Immune system disorders |
E.1.2 | System Organ Class | 10021428 - Immune system 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 evaluate the long-term efficacy and safety of ALX-0061 administered subcutaneously (s.c.) to subjects with active RA. |
Evaluar la eficacia y la seguridad a largo plazo de ALX-0061 administrado subcutáneamente (s.c.) a sujetos con AR activa. |
|
E.2.2 | Secondary objectives of the trial |
Not applicable |
No se aplica |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Must have been eligible for one of the preceding Phase IIb studies with ALX-0061 (study ALX0061-C201 or ALX0061-C202), have been randomized to placebo or one of the ALX-0061 arms (subjects randomized to tocilizumab [TCZ] in study ALX0061-C202 are not eligible), and completed the entire treatment and assessment period of the preceding studies (i.e., 24 weeks for Study ALX0061-C201 and 12 weeks for Study ALX0061-C202). ? Must have reached at least 20% improvement in SJC and/or TJC (66/68 counts) at Week 24 for subjects participating in the preceding Phase IIb ALX0061-C201 study, or at Week 12 for subjects participating in the preceding Phase IIb ALX0061-C202 study.
A complete list of selection criteria can be found in the body of the Clinical Study Protocol. |
- Haber sido elegible para uno de los estudios de Fase IIb previos con ALX-0061 (estudios ALX0061-C201 o ALX0061-C202), haber sido aleatorizado a uno de los grupos de placebo o de ALX-0061 (no serán elegibles los sujetos aleatorizados a tocilizumab [TCZ] en el estudio ALX0061-C202), y haber completado todo el período de tratamiento y evaluación del estudio previo (esto es, 24 semanas en el Estudio ALX0061-C201 y 12 semanas en el Estudio ALX0061-C202). - Haber alcanzado una mejoría de como mínimo el 20% en RAT y/o RAD (recuentos 66/68) en la Semana 24 en el caso de los sujetos participantes en el estudio de Fase IIb previo ALX0061-C201, o en la Semana 12 en el caso de los sujetos participantes en el estudio de Fase IIb previo ALX0061-C202. |
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E.4 | Principal exclusion criteria |
The main criteria for exclusion include the following: ? Received TCZ during the previous Study ALX0061-C202. ? Received any prohibited treatment during the previous Phase IIb ? Diagnosis of or suspicion of a serious infection ? Diagnosis of malignancy or demyelinating disease during the preceding study. ? Any active or recurrent viral infection that based on the Investigator´s clinical assessment make the subject unsuitable for the study. ? Diagnosis of congestive heart failure (CHF) class III or IV, unstable angina pectoris, myocardial infarction, cerebrovascular accident during the preceding study. ? Abnormality in laboratory test results observed at the Week 22 Visit for subjects participating in the preceding Phase IIb ALX0061-C201 study, or observed at the Week 10 Visit for subjects participating in the preceding Phase IIb ALX0061-C202 study.
A complete list of selection criteria can be found in the body of the Clinical Study Protocol. |
Los principales criterios de exclusión son los siguientes:? - Haber recibido TCZ durante el estudio ALX0061-C202 previo. - Haber recibido cualquier tratamiento prohibido durante los estudios de Fase IIb previos (ALX0061-C201 o ALX0061-C202). - Diagnóstico o sospecha de infección grave (que requiera la administración de antibióticos parenterales y/u hospitalización) o tuberculosis (TB) durante el estudio previo. - Diagnóstico de neoplasia maligna o enfermedad desmielinizante durante el estudio previo. - Cualquier infección vírica activa o recurrente que, según la valoración clínica del Investigador, haga que el sujeto no sea adecuado para participar en el estudio, como el herpes zóster recurrente/diseminado. - Diagnóstico de insuficiencia cardíaca congestiva (ICC) de clase III o IV según la definición de la New York Heart Association, angina inestable, infarto de miocardio o accidente vascular cerebral durante el estudio previo. - Anomalía en los resultados de laboratorio de la visita de la Semana 22 en los sujetos participantes en el estudio de Fase IIb previo ALX0061-C201, o de la visita de la Semana 10 en los sujetos participantes en el estudio de Fase IIb previo ALX0061-C202.
Una lista completa de los criterios de selección se puede encontrar en el protocolo |
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E.5 End points |
E.5.1 | Primary end point(s) |
- ACR20, ACR50, and ACR70 response over time. - Disease activity: Disease Activity Score using 28 joint counts (DAS28 using CRP and erythrocyte sedimentation rate [ESR]), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI). - EULAR DAS28 response (good, moderate, or no response). - Remission using disease remission parameters: DAS28, SDAI, CDAI, Boolean. - Health Assessment Questionnaire-Disability Index (HAQ-DI). - Physical and mental component scores of Short Form Health Survey (SF-36). - Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue).
Pharmacokinetics: ? Determination of ALX-0061 serum levels.
Safety: ? Safety assessments will include: - Physical examinations. - Vital sign measurements - Clinical laboratory assessments - Adverse events
Immunogenicity: ? Determination of anti-ALX-0061 antibodies (ADA) |
- Respuesta ACR20, ACR50 y ACR70 a lo largo del tiempo. - Actividad de la enfermedad: Puntuación de Actividad de la Enfermedad (Disease Activity Score, DAS) basada en el recuento de 28 articulaciones (DAS28, utilizando el valor de PCR y la velocidad de sedimentación globular [VSG]), el índice de actividad de la enfermedad simplificado (IAES) y el índice clínico de la actividad de la enfermedad (ICAE). - Respuesta del DAS28 según el EULAR (buena, moderada o sin respuesta). - Remisión, utilizando los parámetros de remisión de la enfermedad: DAS28, IAES, ICAE y definición basada en el análisis Booleano. - Cuestionario de evaluación de la salud - Índice de discapacidad (Health Assessment Questi onnaire-Disability Index, HAQ-DI). - Puntuaciones de los componentes físico y mental de la Short Form Health Survey (SF-36). - Evaluación funcional del tratamiento en la enfermedad crónica ? Fatiga (Functional Assessment of Chronic Illness Therapy-Fatigue, FACIT-Fatiga). - Farmacocinética Determinación de los niveles séricos de ALX-0061.
- Seguridad: Exploraciones físicas. Determinaciones de las constantes vitales Determinaciones de laboratorio Acontecimientos adversos
- Inmunogenicidad Determinación de anticuerpos anti-ALX-0061 (AAF) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 104 weeks evaluation for secondary endopoints mentioned bove (first 7 bullet points)
Pharmacokinetics: up to 104 weeks Safety: up to 114 weeks Immunogenicity: up to 114 weeks |
Hasta 104 semanas evaluacion para los criterios de evaluacion mencionados arriba (las primero 7 puntos)
Farmacocinética: Hasta 104 semanas Seguridad: Hasta 114 semanas Inmunogenicidad: Hasta 114 semanas |
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E.5.2 | Secondary end point(s) |
Not Applicable |
No se aplica |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Not Applicable |
No se aplica |
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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 | 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) | 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 | No |
E.8.1.2 | Open | Yes |
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 | No |
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
| 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 56 |
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 |
Bulgaria |
Czech Republic |
Georgia |
Germany |
Hungary |
Macedonia, the former Yugoslav Republic of |
Mexico |
Moldova, Republic of |
Poland |
Romania |
Serbia |
Spain |
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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
|
last visit of the last subject |
la ultima visita del ultimo sujeto |
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |