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A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Failed on One Prior Anti-TNF Therapy (RESET)

6 de julio de 2017 actualizado por: Hoffmann-La Roche

Rituximab Phase IIIb Open-label, Multi-centre Assessment of Safety and Effectiveness in Patients With RA Following an Inadequate Response to One Prior Anti-TNF Inhibitor (RESET)

This study will evaluate the safety and effectiveness of MabThera (rituximab) in patients with active rheumatoid arthritis who are receiving methotrexate, and who have a previous or current inadequate response to one prior anti-TNF therapy. All patients will receive MabThera 1000 mg as an intravenous infusion on days 1 and 15. After the initial study phase of 24 weeks, eligible patients may receive one re-treatment with MabThera. The anticipated time on study treatment is 48 weeks.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

120

Fase

  • Fase 3

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Canadá
    • Alberta
      • Edmonton, Alberta, Canadá, T6G 2B7
      • Edmonton, Alberta, Canadá, T5M 0H4
    • British Columbia
      • Kelowna, British Columbia, Canadá, V1Y 3G8
      • Vancouver, British Columbia, Canadá, V5Z 3Y1
      • Victoria, British Columbia, Canadá, V8V 3P9
    • Manitoba
      • Winnipeg, Manitoba, Canadá, R3A 1M4
    • Newfoundland and Labrador
      • St John's, Newfoundland and Labrador, Canadá, A1A 5E8
      • St John's, Newfoundland and Labrador, Canadá, A1C 5B8
    • Ontario
      • Hamilton, Ontario, Canadá, L8N 1Y2
      • Hamilton, Ontario, Canadá, L8S 4J9
      • Mississauga, Ontario, Canadá, L5M 2V8
      • Nepean, Ontario, Canadá, K2G 6E2
      • Ottawa, Ontario, Canadá, K1H 8L6
      • Ottawa, Ontario, Canadá, K1S 1C2
      • Thunder Bay, Ontario, Canadá, P7B 5G3
      • Toronto, Ontario, Canadá, M4K 1N2
      • Toronto, Ontario, Canadá, M5T 2S8
      • Toronto, Ontario, Canadá, M5G 1X5
      • Windsor, Ontario, Canadá, N8X 5A6
    • Quebec
      • Laval, Quebec, Canadá, H7G 2E6
      • Montreal, Quebec, Canadá, H1T 2M4
      • Montreal, Quebec, Canadá, H3T 1E2
      • Montreal, Quebec, Canadá, H2L 1S6
      • Montreal, Quebec, Canadá, H2L 4M1
      • Quebec City, Quebec, Canadá, G1V 3M7
      • Sainte-foy, Quebec, Canadá, G1W 4R4
      • Sherbrooke, Quebec, Canadá, J1H 5N4
      • St-eustache, Quebec, Canadá, J7P 4J2
      • Trois-rivieres, Quebec, Canadá, G8Z 1Y2
  • Suecia
      • Boras, Suecia, 50182
      • Falun, Suecia, 79182
      • Goeteborg, Suecia, 41345
      • Jonkoping, Suecia, 551 85
      • Kalmar, Suecia, 39185
      • Karlskrona, Suecia, 37185
      • Lulea, Suecia, 97180
      • Malmoe, Suecia, 20502
      • Oskarstroem, Suecia, 31392
      • Skoevde, Suecia, 54185
      • Stockholm, Suecia, 18288
      • Sundsvall, Suecia, 85186

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 80 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • Adult patients, 18-80 years of age
  • Moderate to severe active rheumatoid arthritis
  • Inadequate response to a single previous or current treatment with an anti-TNF agent
  • Methotrexate for at least 12 weeks, at a stable dose over the past 4 weeks

Exclusion Criteria:

  • Previous treatment with MabThera
  • Use of an anti-TNF agent within past 8 weeks (4 in the case of etanercept)
  • Concurrent treatment with any Disease Modifying Anti-Rheumatic Drug (DMARD) other than methotrexate
  • Active infection, or history of serious or chronic infection

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Brazo único
Droga: rituximab
1000 mg intravenously on Days 1 and 15

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary
Periodo de tiempo: Days 1, 2, 15, and 16 and Week 48 of Initial treatment period
Percentage of participants who reported an AE or serious AE (SAE), a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died.
Days 1, 2, 15, and 16 and Week 48 of Initial treatment period

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary
Periodo de tiempo: Days 1, 2, 15, and 16 and Week 48 of Re-treatment period
Percentage of participants who reported an AE or SAE, a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died.
Days 1, 2, 15, and 16 and Week 48 of Re-treatment period
Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period
Periodo de tiempo: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
ACR20/50/70, defined as ≥20 percent (%), 50%, or 70% improvement, respectively, compared to baseline in tender joint count (TJC) and swollen joint count (SJC), and 20%/50%/70% improvement in at least 3 of 5 additional ACR core set variables: Patient Assessment of Pain; Patient's Global Assessment of Disease Activity; Physician's Global Assessment of Disease Activity; Health Assessment Questionnaire - Disability Index (HAQ-DI); and an acute phase reactant (erythrocyte sedimentation rate [ESR] or C-Reactive Protein [CRP]). If CRP was missing or not done, then ESR was used.
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Initial Treatment Period
Periodo de tiempo: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Complete clinical response was defined as having an ACR70 for at least 13 weeks.
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period
Periodo de tiempo: Weeks 12 and 24 of Re-treatment period
ACR20/50/70, defined as ≥20%, 50%, or 70% improvement, respectively, compared to baseline in TJC and SJC, and 20%/50%/70% improvement in at least 3 of 5 additional ACR core set variables: Patient Assessment of Pain; Patient's Global Assessment of Disease Activity; Physician's Global Assessment of Disease Activity; HAQ-DI; and an acute phase reactant (ESR or CRP). If CRP was missing or not done, then ESR was used.
Weeks 12 and 24 of Re-treatment period
Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Re-Treatment Period
Periodo de tiempo: Weeks 12 and 24 of Re-treatment period
Complete clinical response was defined as having an ACR70 for at least 13 weeks.
Weeks 12 and 24 of Re-treatment period
Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period
Periodo de tiempo: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
The EULAR response criteria were based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none. The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score less than or equal to [≤]3.2), moderate (DAS28 score greater than [>]3.2 but ≤5.1), or high (DAS28 score >5.1). A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period
Periodo de tiempo: Weeks 12 and 24 of Re-treatment period
The EULAR response criteria were based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none. The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1). A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
Weeks 12 and 24 of Re-treatment period
Change From Baseline in DAS28 During the Initial Treatment Period
Periodo de tiempo: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1). A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria. A change of 1.2 units in DAS28 in an individual participant was considered a significant change.
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Change From Baseline in DAS28 During the Re-Treatment Period
Periodo de tiempo: Weeks 12 and 24 of Re-treatment period
The DAS28 scoring used 4 core components: SJC, TJC, Patient Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1). A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria. A change of 1.2 units in DAS28 in an individual participant was considered a significant change.
Weeks 12 and 24 of Re-treatment period
Change From Baseline in SJC During the Initial Treatment Period
Periodo de tiempo: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Change From Baseline in SJC During the Re-Treatment Period
Periodo de tiempo: Weeks 12 and 24 of Re-treatment period
Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
Weeks 12 and 24 of Re-treatment period
Change From Baseline in TJC During the Initial Treatment Period
Periodo de tiempo: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Change From Baseline in TJC During the Re-Treatment Period
Periodo de tiempo: Weeks 12 and 24 of Re-treatment period
Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
Weeks 12 and 24 of Re-treatment period
Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period
Periodo de tiempo: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Physician Global Assessment of Disease Activity was measured using a 100-mm visual analog scale (VAS) where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The physician marked the line and the distance from the left edge was measured in mm.
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Change From Baseline in Physician's Global Assessment of Disease Activity During the Re-Treatment Period
Periodo de tiempo: Weeks 12 and 24 of Re-treatment period
Physician Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The physician marked the line and the distance from the left edge was measured in mm.
Weeks 12 and 24 of Re-treatment period
Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period
Periodo de tiempo: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Patient Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The participant was asked to marked the line and the distance from the left edge was measured in mm.
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Change From Baseline in Patient Global Assessment of Disease Activity During the Re-Treatment Period
Periodo de tiempo: Weeks 12 and 24 of Re-treatment period and Week 4 after last maintenance
Patient Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The participant was asked to marked the line and the distance from the left edge was measured in mm.
Weeks 12 and 24 of Re-treatment period and Week 4 after last maintenance
Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period
Periodo de tiempo: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Patient Global Assessment of Pain was measured using a 100-mm VAS where the extreme left end of the line was 0 = no pain and the extreme right end of the line was 100 = unbearable pain. The participant was asked to mark the line and the distance from the left edge was measured in mm.
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Change From Baseline in Patient Global Assessment of Pain During the Re-Treatment Period
Periodo de tiempo: Weeks 12 and 24 of Re-treatment period
Patient Global Assessment of Pain was measured using a 100-mm VAS where the extreme left end of the line was 0 = no pain and the extreme right end of the line was 100 = unbearable pain. The participant was asked to mark the line and the distance from the left edge was measured in mm.
Weeks 12 and 24 of Re-treatment period
Change From Baseline HAQ-DI Score During the Initial Treatment Period
Periodo de tiempo: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
HAQ-DI: 20 questions, 8 categories of functioning: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common usual activities. Participants report amount of difficulty in performing 2-3 specific subcategory items. Difficulty score is from 0 to 3 (0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; and 3 = unable to do). The highest component score in each of the 8 categories determined the score for that category, unless aids, devices, and/or help from another person were required which = a score of 2 (unless already 2 or 3). The 8 category scores were averaged into overall HAQ-DI score ranging from 0 to 3 (0 to 1 = mild to moderate difficulty; 1 to 2 = moderate to severe disability; and 2 to 3 = severe to very severe disability). HAQ-DI not computed if > 2 categories were missing.
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Change From Baseline HAQ-DI Score During the Re-Treatment Period
Periodo de tiempo: Weeks 12 and 24 of Re-treatment period
HAQ-DI: 20 questions, 8 categories of functioning: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common usual activities. Participants report amount of difficulty in performing 2-3 specific subcategory items. Difficulty score is from 0 to 3 (0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; and 3 = unable to do). The highest component score in each of the 8 categories determines the score for that category, unless aids, devices, and/or help from another person were required which = a score of 2 (unless already 2 or 3). The 8 category scores were averaged into overall HAQ-DI score ranging from 0 to 3 (0 to 1 = mild to moderate difficulty; 1 to 2 = moderate to severe disability; and 2 to 3 = severe to very severe disability). HAQ-DI not computed if >2 categories were missing.
Weeks 12 and 24 of Re-treatment period
Change From Baseline in ESR During the Initial Treatment Period
Periodo de tiempo: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
ESR was measured in mm/hour and was used to determine the acute phase response. Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr.
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Change From Baseline in ESR During the Re-Treatment Period
Periodo de tiempo: Weeks 12 and 24 of Re-treatment period
ESR was measured in mm/hour and was used to determine the acute phase response. Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr.
Weeks 12 and 24 of Re-treatment period
Change From Baseline in CRP During the Initial Treatment Period
Periodo de tiempo: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
CRP levels were measured in milligrams/liter (mg/L) and were used to determine the acute phase response. A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L.
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Change From Baseline CRP During the Re-Treatment Period
Periodo de tiempo: Weeks 12 and 24 of Re-treatment period
CRP levels were measured in mg/L and were used to determine the acute phase response. A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L.
Weeks 12 and 24 of Re-treatment period
Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period
Periodo de tiempo: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1). A DAS28 score ≤2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Percentage of Participants With Disease Remission According to DAS28 in the Re-Treatment Period
Periodo de tiempo: Weeks 12 and 24 of Re-treatment period
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1). A DAS28 score ≤2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
Weeks 12 and 24 of Re-treatment period
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period
Periodo de tiempo: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Participant fatigue was evaluated using the FACIT-F scale, a 13-item questionnaire in which the participants were requested to score each item on a 5-point scale. The FACIT-F scores ranged from 0 to 52, with higher scores representing less fatigue. Score changes of 4 points or more were considered clinically meaningful. The total score was a summation of all 13 items, where 2 of the positive items (I have energy; I am able to do my usual activities) were reversed for scoring.
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
Change From Baseline in FACIT-F Total Score During the Re-Treatment Period
Periodo de tiempo: Weeks 12 and 24 of Re-treatment period
Participant fatigue was evaluated using the FACIT-F scale, a 13-item questionnaire in which the participants were requested to score each item on a 5-point scale. The FACIT-F scores ranged from 0 to 52, with higher scores representing less fatigue. Score changes of 4 points or more were considered clinically meaningful. The total score was a summation of all 13 items, where 2 of the positive items (I have energy; I am able to do my usual activities) were reversed for scoring.
Weeks 12 and 24 of Re-treatment period

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Hoffmann-La Roche

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

18 de julio de 2006

Finalización primaria (Actual)

12 de marzo de 2009

Finalización del estudio (Actual)

12 de marzo de 2009

Fechas de registro del estudio

Enviado por primera vez

7 de enero de 2011

Primero enviado que cumplió con los criterios de control de calidad

7 de enero de 2011

Publicado por primera vez (Estimar)

10 de enero de 2011

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

15 de agosto de 2017

Última actualización enviada que cumplió con los criterios de control de calidad

6 de julio de 2017

Última verificación

1 de junio de 2017

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • ML20381

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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