E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Rheumatoid Arthritis with an Inadequate Response to Methotrexate With or Without TNF Inhibitors |
Artritis reumatoide de moderada a grave con respuesta inadecauda a metotrexato con o sin inhibidores del TNF |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis |
Artritis reumatoide |
|
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 | 18.1 |
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 |
The purpose of this study is to determine whether the study drug, BMS-986142, is safe and effective in treating moderate to severe rhematoid arthritis in subjects with an inadequate response to methotrexate or methotrexate and up to 2 TNF Inhibitors. Patients who qualify will be randomized to either one of 3 doses of BMS-986142 or placebo in 1:1:1:1 randomization for 12 weeks. Disease activity and safety will be assessed over the course of the study. |
El objetivo de este estudio es determinar si el medicamento en estudio, BMS-986142, es seguro y eficaz en el tratamiento de la artritis reumatoide de moderada a grave en sujetos con respuesta inadecuada a metotrexato o metotrexato y hasta 2 inhibidores del TNF. Los pacientes cualificados serán aleatorizados a una de las 3 dosis de BMS-986142 o a placebo en la randomización 1:1:1:1 durante 12 semanas. La actividad de la enfermedad y la seguridad serán evaluadas durante el curso del estudio. |
|
E.2.2 | Secondary objectives of the trial |
1) Assess additional efficacy outcomes of BMS-986142 at Week 12 and over 12 weeks of treatment as measured by ACR20, ACR50 and ACR70 response rates, DAS28-CRP change from baseline, DAS28-ESR change from baseline, Clinical Disease Activity Index ( CDAI), Simplified Disease Index (SDAI), and Boolean remission. 2) Assess the safety and tolerability of BMS-986142. 3) Evaluate pre-dose concentration (Ctrough) of BMS-986142. 4) Assess the efficacy of BMS-986142+MTX to -MTX in reducing synovitis, osteitis, bone erosions, and cartilage loss in hands/wrists by MRI at Weeks 4, and 12 from baseline. |
1. Evaluar los resultados de eficacia adicionales de BMS-986142 en la semana 12 y después de 12 semanas de tratamiento medida por las tasas de respuesta ACR20, ACR50 y ACR70, cambio respecto al basal en DAS28-PCR, cambio respecto al basal en DAS28-VSG, Índice de la actividad clínica de la enfermedad (CDAI), Índice simplificado de la enfermedad (SDAI) y remisión booleana. 2. Evaluar la seguridad y tolerabilidad de BMS-986142. 3. Evaluar la concentración pre-dosis (Cvalle) de BMS-986142. 4. Evaluar la eficacia de BMS-986142+MTX versus -MTX en la reducción de la sinovitis, osteítis, erosiones óseas y pérdida de cartílago en manos/muñecas por RM en las semanas 4 y 12 respecto al basal. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female age 18 and above - Diagnosed with active rheumatoid arthritis (RA) by standard criteria at least 16 weeks before screening, have functional ACR class I-III - Have an inadequate response to methotrexate - In addition to an inadequate response to methotrexate have an inadequate response or intolerance to 1 but not more than 2 TNF inhibiotrs - Have a minimum of 6 swollen and 6 tender joints (from 66/68 joint count) - Have hsCRP of ? 0.8 mg/dL (8mg/L) [by central laboratory values] or an ESR ? 28 mm/hr - Willing to use effective birth control for the entire length of the study |
- Hombres y mujeres de 18 años de edad o más - Con diagnóstico de artritis reumatoide (AR) activa según los criterios estándar al menos 16 semanas antes de la selección, con clase del estado funcional global CR de 1 a 3. - Con respuesta inadecuada a metotrexato - Además de presentar respuesta inadecuada a metotrexato, tienen una falta de respuesta o intolerancia a 1 pero no más de 2 inhibidores del TNF. - Tener un mínimo de 6 articulaciones inflamadas y 6 articulaciones dolorosas (en el recuento de 66/68 articulaciones) - Los sujetos deben tener una PCRus de ? 0,8 mg/dl (8 mg/l) [según los valores del laboratorio central] o una VSG ? 28 mm/h - Estar dispuestos a utilizar anticonceptivos eficaces durante la duración del estudio |
|
E.4 | Principal exclusion criteria |
- Diagnosed with juvenile Rheumatoid Arthritis - Have been treated with other biologic treatment than a TNF inhibitor - Active systemic bacterial, viral or fungal infection or evidence of prior or current Hepatitis B or C infection or HIV infection, latent bacterial, viral or fungal infections - Have been treated with Intramuscular or Intra-articular glucocorticosteroids within 4 weeks of randomization - Taking Oral steroids at dose above 10 mg/day of prednisone (or prednisone equivalents) - Have other autoimmune disease other than RA like lupus, multiple sclerosis - Have significant concurrent medical condition at the time of screening or baseline visit |
- Diagnosticados con Artritis reumatoide juvenil - Que hayan sido con otros biológicos distintos a los inhibidores del TNF. - Infección sistémica bacteriana activa, vírica o fúngica o con antecedentes de Hepatitis B o C demostrada o antecedentes o infección por el virus de la inmunodeficiencia humana (VIH) demostrada, infecciones latentes bacterianas, víricas o fúngicas - Que hayan sido tratados con glucocorticoides intramusculares o intra-articulares en las 4 semanas previas a la aleatorización. - Que tomen esteroides orales a una dosis superior a 10 mg/día de prednisona (o equivalentes de prednisona) - Sujetos con otra enfermedad autoinmunitaria que no sea AR como lupus, esclerosis múltiple - Que padezcan cualquier otra condición médica concomitante en el momento de la visita de selección |
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E.5 End points |
E.5.1 | Primary end point(s) |
Co-Primary: - Proportion of subjects who achieve ACR70 response rate at Week 12 - Proportion of subjects who achieve ACR20 response rate at Week 12 |
Co-Principales: - Porcentaje de sujetos que alcanzan una tasa de respuesta ACR70 en la semana 12 - Porcentaje de sujetos que alcanzan una tasa de respuesta ACR20 en la semana 12 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at Week 12 |
en la semana 12 |
|
E.5.2 | Secondary end point(s) |
1/ Proportion of subjects who achieve ACR20, ACR50, ACR70 2/ Proportion of subjects who achieve DAS28-CRP < 2.6 3/ Proportion of subjects who achieve DAS28-ESR < 2.6 4/ Proportion of subjects who achieve CDAI ? 2.8 5/ Proportion of subjects who achieve SDAI ? 3.3 6/ Proportion of subjects who achieve Boolean Remission 7/ Change from baseline in DAS28-CRP score, DAS28-ESR score 8/ Change from baseline in CDAI score, SDAI score 9/ Change from baseline in RAMRIS scores of synovitis, osteitis (bone marrow edema), bone erosion and cartilage loss (joint-space narrowing) (MRI)
10/ Incidence and severity of all Adverse Events (AEs), Serious AEs, and pre-established Events of Special Interest, clinically significant changes in vital signs, clinically significant ECG abnormalities, clinically significant abnormalities in general laboratory tests
11/ Plasma concentration of BMS-986142 |
1/ Porcentaje de sujetos que alcanzan una tasa de respuesta ACR20, ACR50, ACR70 2/ Porcentaje de sujetos que alcanzan una tasa de respuesta DAS28-PCR < 2,6 3/ Porcentaje de sujetos que alcanzan una tasa de respuesta DAS28-VSG < 2,6 4/ Porcentaje de sujetos que alcanzan una tasa de respuesta CDAI ? 2,8 5/ Porcentaje de sujetos que alcanzan una tasa de respuesta SDAI ? 3,3 6/ Porcentaje de sujetos que alcanzan una tasa de respuesta de Remisión Booleana 7/ Cambio desde el basal en la puntuación DAS28-PCR, puntuación DAS28-VSG 8/ Cambio desde el basal en la puntuación CDAI, puntuación SDAI 9/ Cambio desde el basal en las puntuaciones RAMRIS de sinovitis, osteítis (edema de la médula ósea), erosión ósea y pérdida de cartílago (estrechamiento del espacio articular) (IRM) 10/ Incidencia y gravedad de todos los acontecimientos adversos (AA), acontecimientos adversos graves y acontecimientos preestablecidos de especial interés 11/ Concentración plasmática de BMS-986142 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/ to 6/ over time from baseline to Week 12 7/ and 8/ over time up to Week 12 9/ to Week 4, and Week 12
10/ During study
11/ Predose at specified time points |
-1/ a 6/ a lo largo del tiempo desde el basal hasta la semana 12 7/ y 8/ a lo largo del tiempo hasta la semana 12 9/ hasta la semana 4, y semana 12 10/ Durante el estudio 11/ Antes de la dosis en los puntos temporales especificados |
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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 | 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 | 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 | Yes |
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 | 4 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 |
Austria |
Belgium |
Brazil |
Canada |
France |
Germany |
Israel |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
Poland |
Russian Federation |
South Africa |
Spain |
Taiwan |
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
|
LVLS |
Última visita del último 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 | 16 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 22 |