E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Rheumatoid Arthritis (RA) |
Artritis reumatoide (AR) activa moderada o grave |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis |
Artritis Reumatoide |
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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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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 evaluate the long-term safety, tolerability, and efficacy of ABT-494 in RA subjects who have completed Study M13-550 or Study M13-537 Phase 2 RCT with ABT-494. |
Evaluar la seguridad, la tolerabilidad y la eficacia a largo plazo de ABT-494 en pacientes con AR que han completado los estudios ECA en fase 2 M13-550 o M13-537 con ABT-494. |
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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 completed Study M13-550 or Study M13-537 with ABT-494 and has not developed any discontinuation criteria, defined in Section 5.4.1 of that study. 2. If the subject has evidence of new latent TB infection, the subject must initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is longer) of an ongoing TB prophylaxis before continuing to receive study drug. 3. If female, subject must meet one of the following criteria: ? Postmenopausal (defined as no menses for at least 1 year). ? Surgically sterile (bilateral oophorectomy or hysterectomy). ? Practicing from the time of screening until at least 30 days after the last dose of study drug at least TWO of the following methods of birth control: - Tubal ligation - Partner vasectomy (at least 6 months earlier) (the vasectomized male partner should be the sole partner for that female subject) - Intrauterine device - A male condom with spermicidal jelly or cream - Diaphragm, contraceptive sponge or cervical cap with spermicidal jelly or cream - Hormonal contraceptives (injected, oral, transdermal or implanted methods) must have been taking at least 2 months prior to dosing 4. Male subjects must agree to follow protocol-specified pregnancy avoidance measures, including refraining from donating sperm, for up to 30 days post last dose of study drug. 5. Subjects must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures. 6. Subject is judged to be in good health as determined by the Investigator based on the results of medical history, physical examination and laboratory profile performed. |
1. Pacientes que han completado los estudios M13-550 o M13-537 con ABT-494 y no han desarrollado ninguno de los criterios de retirada que se definen en la sección5.4.1 de esos estudios. 2. Si el paciente tiene indicios de TB latente nueva, debe iniciar y completar como mínimo 2 semanas (o siguiendo las normas locales, el período más largo de ambos) de profilaxis continuada para la TB antes de continuar recibiendo el fármaco del estudio. 3. En el caso de las mujeres, las pacientes deberán cumplir uno de los criterios siguientes: ? Ser posmenopáusicas (lo que se define como la ausencia de menstruación durante al menos 1 año). ? Haberse sometido a esterilización quirúrgica (ovariectomía bilateral o histerectomía). ? Usar desde el momento de la selección hasta al menos 30 días después de la última dosis del fármaco del estudio al menos DOS de los métodos anticonceptivos siguientes: o Ligadura de trompas o Vasectomía de la pareja (al menos 6 meses antes) (la pareja vasectomizada debe ser la única pareja de la paciente femenina) o Dispositivo intrauterino o Preservativo masculino con gel o crema espermicidas o Diafragma, esponja anticonceptiva o capuchón cervical con gel o crema espermicidas o Los anticonceptivos hormonales (inyectables, orales, transdérmicos o implantados) deben haberse estado utilizando durante al menos 2 meses antes de la administración. 4. Los hombres deben aceptar las medidas de evitación del embarazo que se especifican en el protocolo, incluida la abstención de donar esperma hasta 30 días después de la última dosis del fármaco del estudio. 5. Los pacientes deberán firmar voluntariamente y fechar un documento de consentimiento informado, aprobado por un Comité Ético de Investigación Clínica (CEIC), antes de iniciar cualquiera de los procedimientos específicos del estudio. 6. Se considera que el estado de salud del paciente es bueno, según determine el investigador a partir de la historia clínica, la exploración física y los resultados de laboratorio. |
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E.4 | Principal exclusion criteria |
1. Pregnant or breastfeeding female. 2. Ongoing infections at Week 0 that have NOT been successfully treated. Subjects with ongoing infections undergoing treatment may be enrolled BUT NOT dosed until the infection has been successfully treated. 3. Anticipated requirement or receipt of any live vaccine during study participation including up to 30 days after the last dose of study drug. 4. Laboratory values from the visit immediately prior to Baseline Visit meeting the following criteria: ? Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 3.0 × ULN ? Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73m2 ? Total white blood cell count (WBC) < 2,000/µL ? Absolute neutrophil count (ANC) < 1,000/µL ? Platelet count < 50,000/µL ? Absolute lymphocytes count < 500/µL ? Hemoglobin < 8 gm/dL 5. Enrollment in another interventional clinical study while participating in this study. 6. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive study drug. |
1. Mujeres embarazadas o lactantes. 2. Infecciones en curso en la semana 0 que NO han sido tratadas con éxito. Los pacientes con infecciones en curso que reciben tratamiento pueden inscribirse en el estudio PERO NO recibirán el fármaco hasta que la infección haya sido tratada satisfactoriamente. 3. Se espera que se requiera o se administra una vacuna atenuada durante la participación en el estudio, incluidos hasta 30 días después de la última dosis del fármaco del estudio. ABT-494 Protocolo M13-538 EudraCT 2013-003530-33 5 Criterios principales de exclusión (continuación): 4. Los resultados de laboratorio de la visita inmediatamente anterior a la visita inicial cumplen los criterios siguientes: ? Aspartato aminotransferasa (AST) o alanina aminotransferasa (ALT) > 3,0 veces el LSN en suero ? Filtración glomerular estimada según la fórmula simplificada de 4 variables de la Modificación de la Dieta en la Nefropatía (Modification of Diet in Renal Disease, MDRD) < 40 ml/min/1,73 m2 ? Recuento total de leucocitos < 2.000/?l ? Recuento absoluto de neutrófilos (RAN) < 1.000/?l ? Recuento de plaquetas <50.000 /?l ? Recuento absoluto de linfocitos < 500/?l ? Hemoglobina < 8 g/dl 5. Inclusión en otro estudio clínico intervencionista mientras el paciente participa en este estudio. 6. El investigador considera, por el motivo que sea, el paciente no es un buen candidato para recibir el fármaco del estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
? ACR 20/50/70 response rates ? Change from Baseline in individual ACR components: Tender Joint Count, Swollen Joint Count, Patient?s Assessment of Pain (VAS), Patient?s Global Assessment of Disease Activity, Physician?s Global Assessment of Disease Activity, hsCRP, and health Assessment Questionnaire Disability Index (HAQ-DI) ? Proportion of subjects achieving Low Disease Activity or Clinical Remission, and the Proportion of subjects achieving Clinical Remission. ? Change from Baseline in DAS28 [CRP] disease activity score, CDAI and Patient Reported Outcomes including FACIT-Fatigue Scale, RA-WIS, and EQ-5D ? Incidence of adverse events, changes in vital signs, physical examination results and clinical laboratory data |
-Tasas de respuesta ACR20/50/70 - variación con respecto al valor inicial de cada componente ACR en las semanas 6, 12, 24, 36, 48, 60, 72, 84 y 96: RAD, RAI, evaluación del dolor realizada por el paciente (VAS), evaluación global de la actividad de la enfermedad realizada por el paciente, evaluación global de la actividad realizada por el médico, índice de discapacidad según el cuestionario de evaluación de la salud (HAQ-DI) y PCR-as proporción de pacientes que consigan una actividad baja de la enfermedad (LDA) o la remisión clínica (RC) variación con respecto a la puntuación inicial de la actividad de la enfermedad DAS28 [PCR], CDAI y los resultados comunicados por el paciente, incluidos la escala de cansancio: FACIT y los cuestionarios RA-WIS y EQ-5D Las evaluaciones de seguridad consistirán en el seguimiento de los acontecimientos adversos, exploraciones físicas, medición de las constantes vitales y análisis clínicos (hematología, bioquímica y análisis de orina). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
? Weeks 6, 12, 24, 36, 48, 60, 72, 84, and 96 ? For AE's: Week 0 through 30 day follow-up visit (30 days after last dose of study drug) |
Semanas 6, 12, 24, 36, 48, 60, 72, 84, y 96 Para AA: Semana de 0 a 30 días a la visita de seguimiento (30 días después de la última dosis del fármaco del estudio) |
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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 | No |
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 | 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.8.2.4 | 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 | 67 |
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 |
Australia |
Canada |
Chile |
Colombia |
European Union |
Israel |
Mexico |
Moldova, Republic of |
Puerto Rico |
Russian Federation |
Serbia |
South Africa |
Turkey |
Ukraine |
United States |
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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
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The end of the trial will be 30 days after the last dose of study drug |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
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 |