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 | 17.1 |
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 |
|
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 assess the efficacy and safety of dose regimens of ALX-0061 administered s.c. in combination with MTX to subjects with active RA despite MTX therapy compared with placebo. |
Evaluar la eficacia y seguridad de distintas pautas de dosificación de ALX-0061, administrado por vía subcutánea (s.c.) en combinación con metotrexato (MTX) a sujetos con AR activa a pesar de la terapia con MTX, en comparación con placebo |
|
E.2.2 | Secondary objectives of the trial |
?To assess the effects of ALX-0061 on quality of life, PK, PD, and immunogenicity of ALX 0061, and to define the optimal dose regimen for ALX 0061, based on safety and efficacy, for further clinical development. |
Evaluar los efectos de ALX-0061 sobre la calidad de vida, la farmacocinética (FC) y la farmacodinámica (FD), así como la inmunogenicidad de ALX 0061, y definir la pauta de dosificación óptima de ALX 0061, basada en la seguridad y la eficacia, para el desarrollo clínico posterior |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The main criteria for inclusion include the following: ? Man or woman ? 18 years and < 75 years of age at the time of signing the informed consent form. ? Diagnosis of RA for at least 6 months prior to screening, and ACR functional class I-III. ? Treated with and tolerating MTX ? Active RA
A complete list of selection criteria can be found in the body of the Clinical Study Protocol |
Los principales criterios de inclusión son los siguientes: - Varones o mujeres ? 18 años y < 75 años de edad en el momento de firmar el documento de consentimiento informado. - Diagnóstico de AR como mínimo 6 meses antes de la selección y una clase funcional del ACR de I-III. - Sujetos tratados con MTX que toleren dicho fármaco, - AR activa
Una lista completa de los criterios de selección se puede encontrar en el protocolo |
|
E.4 | Principal exclusion criteria |
The main criteria for exclusion include the following: ? Have been treated with DMARDs/systemic immunosuppressives other than MTX. ? Have received approved or investigational biological or targeted synthetic DMARD therapies for RA less than 6 months prior to screening. ? Have a history of toxicity, non-tolerance, primary non-response or inadequate response to a biological therapy, or targeted synthetic DMARDs for RA. ? Have received prior therapy blocking the interleukin-6 (IL-6) pathway at any time.
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 sido tratado con fármacos antirreumáticos modificadores de la enfermedad (FARME)/inmunosupresores sistémicos a excepción del MTX, - Haber recibido terapias con FARME sintéticos dirigidos o biológicos, autorizados o en investigación, para la AR con una anterioridad inferior a 6 meses respecto a la selección. - Antecedentes de toxicidad, intolerancia, ausencia de respuesta primaria o respuesta inadecuada a una terapia biológica o a FARME sintéticos dirigidos para el tratamiento de la AR. - Haber recibido previamente terapias bloqueantes de la vía de la interleucina-6 (IL-6) en cualquier momento
Una lista completa de los criterios de selección se puede encontrar en el protocolo |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Reduction of signs and symptoms of RA |
Reduccion de los signos y sintomas de AR |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary 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
- Pharmacodynamics
- Safety
- Immunogenicity |
- 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:
- Farmacodinámica
- Seguridad
- Inmunogenicidad |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
24 weeks evaluation for secondary endopoints mentioned bove (first 7 bullet points)
PK: 24 weeks
PD, safety and immunogenicity: For the complete duration of the study |
24 semanas evaluacion para los criterios de evaluacion mencionados arriba (las primero 7 puntos)
Farmacodinámica: 24 semanas
Farmacodinámica, Seguridad e nmunogenicidad: Por la duracion completa 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 | Yes |
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 | 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 | 5 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
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 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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |