A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Failed on One Prior Anti-TNF Therapy (RESET)
2017年7月6日 更新者：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.
研究概览
研究类型
介入性
注册 (实际的)
120
阶段
- 第三阶段
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Alberta
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Edmonton、Alberta、加拿大、T6G 2B7
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Edmonton、Alberta、加拿大、T5M 0H4
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British Columbia
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Kelowna、British Columbia、加拿大、V1Y 3G8
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Vancouver、British Columbia、加拿大、V5Z 3Y1
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Victoria、British Columbia、加拿大、V8V 3P9
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Manitoba
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Winnipeg、Manitoba、加拿大、R3A 1M4
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Newfoundland and Labrador
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St John's、Newfoundland and Labrador、加拿大、A1A 5E8
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St John's、Newfoundland and Labrador、加拿大、A1C 5B8
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Ontario
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Hamilton、Ontario、加拿大、L8N 1Y2
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Hamilton、Ontario、加拿大、L8S 4J9
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Mississauga、Ontario、加拿大、L5M 2V8
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Nepean、Ontario、加拿大、K2G 6E2
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Ottawa、Ontario、加拿大、K1H 8L6
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Ottawa、Ontario、加拿大、K1S 1C2
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Thunder Bay、Ontario、加拿大、P7B 5G3
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Toronto、Ontario、加拿大、M4K 1N2
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Toronto、Ontario、加拿大、M5T 2S8
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Toronto、Ontario、加拿大、M5G 1X5
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Windsor、Ontario、加拿大、N8X 5A6
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Quebec
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Laval、Quebec、加拿大、H7G 2E6
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Montreal、Quebec、加拿大、H1T 2M4
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Montreal、Quebec、加拿大、H3T 1E2
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Montreal、Quebec、加拿大、H2L 1S6
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Montreal、Quebec、加拿大、H2L 4M1
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Quebec City、Quebec、加拿大、G1V 3M7
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Sainte-foy、Quebec、加拿大、G1W 4R4
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Sherbrooke、Quebec、加拿大、J1H 5N4
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St-eustache、Quebec、加拿大、J7P 4J2
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Trois-rivieres、Quebec、加拿大、G8Z 1Y2
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Boras、瑞典、50182
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Falun、瑞典、79182
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Goeteborg、瑞典、41345
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Jonkoping、瑞典、551 85
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Kalmar、瑞典、39185
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Karlskrona、瑞典、37185
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Lulea、瑞典、97180
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Malmoe、瑞典、20502
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Oskarstroem、瑞典、31392
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Skoevde、瑞典、54185
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Stockholm、瑞典、18288
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Sundsvall、瑞典、85186
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 80年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
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
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：单臂
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1000 mg intravenously on Days 1 and 15
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary
大体时间：Days 1, 2, 15, and 16 and Week 48 of Initial treatment period
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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.
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Days 1, 2, 15, and 16 and Week 48 of Initial treatment period
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary
大体时间：Days 1, 2, 15, and 16 and Week 48 of Re-treatment period
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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.
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Days 1, 2, 15, and 16 and Week 48 of Re-treatment period
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Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period
大体时间：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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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.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Initial Treatment Period
大体时间：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Complete clinical response was defined as having an ACR70 for at least 13 weeks.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period
大体时间：Weeks 12 and 24 of Re-treatment period
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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.
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Weeks 12 and 24 of Re-treatment period
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Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Re-Treatment Period
大体时间：Weeks 12 and 24 of Re-treatment period
|
Complete clinical response was defined as having an ACR70 for at least 13 weeks.
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Weeks 12 and 24 of Re-treatment period
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Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period
大体时间：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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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.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period
大体时间：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.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in DAS28 During the Initial Treatment Period
大体时间：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.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in DAS28 During the Re-Treatment Period
大体时间：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.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in SJC During the Initial Treatment Period
大体时间：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.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in SJC During the Re-Treatment Period
大体时间：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.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in TJC During the Initial Treatment Period
大体时间：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.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in TJC During the Re-Treatment Period
大体时间：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.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period
大体时间：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.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in Physician's Global Assessment of Disease Activity During the Re-Treatment Period
大体时间：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.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period
大体时间：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.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in Patient Global Assessment of Disease Activity During the Re-Treatment Period
大体时间：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.
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Weeks 12 and 24 of Re-treatment period and Week 4 after last maintenance
|
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Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period
大体时间：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
大体时间：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
大体时间：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
|
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Change From Baseline HAQ-DI Score During the Re-Treatment Period
大体时间：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
大体时间：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
大体时间：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.
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Weeks 12 and 24 of Re-treatment period
|
|
Change From Baseline in CRP During the Initial Treatment Period
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2006年7月18日
初级完成 (实际的)
2009年3月12日
研究完成 (实际的)
2009年3月12日
研究注册日期
首次提交
2011年1月7日
首先提交符合 QC 标准的
2011年1月7日
首次发布 (估计)
2011年1月10日
研究记录更新
最后更新发布 (实际的)
2017年8月15日
上次提交的符合 QC 标准的更新
2017年7月6日
最后验证
2017年6月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.