A Phase III Study of Abatacept in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate
2013年8月6日 更新者:Bristol-Myers Squibb
A Phase III, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Abatacept Administered Intravenously in Korean Subjects With Active Rheumatoid Arthritis While Receiving Methotrexate
The purpose of the study is to demonstrate the clinical efficacy of abatacept (body-weight tiered dose approximating 10 mg/kg) compared with placebo on a background of methotrexate after 6 months (Day 169) of treatment in Korean patients with active rheumatoid arthritis and an inadequate clinical response to methotrexate
研究概览
研究类型
介入性
注册 (实际的)
113
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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Anyang、大韩民国、431-070
- Local Institution
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Daegu、大韩民国、705-718
- Local Institution
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Daejeon、大韩民国、302-799
- Local Institution
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Seoul、大韩民国、110-744
- Local Institution
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Seoul、大韩民国、137-040
- Local Institution
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Seoul、大韩民国、138-736
- Local Institution
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Sungdong-Gu
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Seoul、Sungdong-Gu、大韩民国、133-792
- Local Institution
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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 及以上 (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
Key Inclusion Criteria:
- Rheumatoid arthritis (RA) for longer than 1 year from the time of the initial diagnosis of RA
- Patients must have been taking methotrexate for at least 3 months with at least a weekly dose of 15 mg, and a stable dose for 28 days prior to treatment (Day 1)
- Methotrexate weekly dose as low as 10 mg is permitted for patients who cannot tolerate higher doses
Key Exclusion Criteria:
- Evidence (as assessed by the Investigator) of active or latent bacterial or viral infections at the time of potential enrollment
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:随机化
- 介入模型:并行分配
- 屏蔽:双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:Abatacept and Methotrexate
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Intravenous (IV) solution, - weight tiered (500 mg <60 kg); (750 mg 60-100 kg); (1 gram > 100 kg), Day 1, Day 15, Day 29; every 28 days thereafter, 6 months
其他名称:
Tablets, Oral, ≥ 15 mg, weekly, 6 months
Solution, intravenous, 10 mg/kg, every 28 days
其他名称:
Tablets, oral, 15 mg weekly to be adjusted according to patient condition
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安慰剂比较:Placebo and Methotrexate
(standard of care)
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Tablets, Oral, ≥ 15 mg, weekly, 6 months
Tablets, oral, 15 mg weekly to be adjusted according to patient condition
IV solution, Intravenous, D5W, Day 1, Day 15, Day 29; every 28 days thereafter, 6 months
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实验性的:Abatacept - Open Label
Open-label extension phase
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Intravenous (IV) solution, - weight tiered (500 mg <60 kg); (750 mg 60-100 kg); (1 gram > 100 kg), Day 1, Day 15, Day 29; every 28 days thereafter, 6 months
其他名称:
Tablets, Oral, ≥ 15 mg, weekly, 6 months
Solution, intravenous, 10 mg/kg, every 28 days
其他名称:
Tablets, oral, 15 mg weekly to be adjusted according to patient condition
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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 |
---|---|---|
Percentage of Participants Meeting the Criteria of the American College of Rheumatology for 20% Improvement (ACR20)
大体时间:At Day 169
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The ACR 20 is based on 20% improvement (compared with baseline values) in tender and swollen joint counts and on 20% improvement in 3 of the remaining 5 core set measures (participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function) and 1 acute phase reactant value.
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At Day 169
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Long-term Extension (LTE) (Open-Label) Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuatons Due to SAEs, Adverse Events (AEs), Related AEs, and Discontinuations Due to AEs
大体时间:Day 169 to up to 56 days post the last dose (Day 1485) in the LTE period
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AE=any new untoward medical occurrence or worsening of a preexisting medical condition which does not necessarily have a causal relationship with this treatment.
Related AE=relationship of certain, probable, possible, or missing.
SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
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Day 169 to up to 56 days post the last dose (Day 1485) in the LTE period
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Percentage of Participants With American College of Rheumatology (ACR) ACR50 and ACR70 Response at Day 169
大体时间:At Day 169
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The ACR defines ACR 50 and ACR70 response as a 50% or 70% improvement (compared with baseline values) in tender and swollen joint counts and 50% or 70% improvement in 3 of the remaining 5 core set measures (patient global assessment of pain, patient global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function) and 1 acute phase reactant value (C-reactive protein).
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At Day 169
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Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components
大体时间:From Baseline to Day 169
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The ACR defines improvement in core components as 20%, 50%, or 70% improvement in tender and swollen joint counts and 3 of the remaining core components: patient global assessment of disease activity, physician global assessment of disease activity, patient assessment of pain, patient self-assessed disability (Health Assessment Questionnaire Disability Index [HAQ-DI]), and levels of 1 acute phase reactant (C-reactive protein levels or erythrocyte sedimentation rate.)
The HAQ-DI assesses a patient's level of functional ability via 20 questions in 8 categories of functioning; scale=0 (no disability) to 3 (completely disabled); total possible score=24.
The higher the score, the greater the disability.
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From Baseline to Day 169
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Change From Baseline in Disease Activity Scores (DAS) Based on C-reactive Protein (DAS 28 [CRP]) Levels or Erythrocyte Sedimentation Rate (DAS 28[ESR])
大体时间:From Baseline to Days 169 and 1485
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Adjusted mean change from baseline.
The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of rheumatoid arthritis (>5.1=high disease activity; <3.2=low disease activity; <2.6=remission).
CRP or ESR give estimations of DAS28 values on a group level.
Change from Baseline=Postbaseline - Baseline value.
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From Baseline to Days 169 and 1485
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Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score
大体时间:From Baseline to Day 169
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Adjusted mean change from baseline.
The HAQ-DI assesses a patient's level of functional ability via 20 questions in 8 categories of functioning.
Patients respond on a scale from 0 (no disability) to 3 (completely disabled); total possible score=24.
Higher score indicates greater disability.
Change from baseline= postbaseline - baseline value.
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From Baseline to Day 169
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Change From Baseline to Day 169 in Analysis of Short-Form 36 (SF-36) Health Survey Questionnaire Domains
大体时间:From Baseline to Day 169
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Adjusted mean change from baseline.
The SF-36 is a 36-item self-administered questionnaire developed to assess health-related quality of life and comprised of 8 domains( including 4 physical and 4 mental subscales) used to derive the physical and mental component summary scores.
All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population.
The scores range from 0 to 100, with a higher score indicating better quality of life.
Change from baseline=postbaseline - baseline value.
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From Baseline to Day 169
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Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period
大体时间:Throughout double-blind study period (up to Day 169); table includes data up to 56 days past double-blind period or start of the open-label period, whichever occurred first.
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AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment.
Related AE=relationship of certain, probable, possible, or missing.
SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
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Throughout double-blind study period (up to Day 169); table includes data up to 56 days past double-blind period or start of the open-label period, whichever occurred first.
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Abatacept Pharmacokinetic (PK) Parameters: Time to Maximum Concentration (Tmax) and Half-Life of Elimination (T-Half)
大体时间:At the end of infusion and 2 to 4 hours after the start of infusion on Day 85, at anytime between Day 92 and 96, and pre-dose on Day 113
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Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg.
Tmax = the time after administration of a drug when the maximum plasma concentration is reached; when the rate of absorption equals the rate of elimination.
T-Half = the biological half-life or elimination half life of a substance is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity.
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At the end of infusion and 2 to 4 hours after the start of infusion on Day 85, at anytime between Day 92 and 96, and pre-dose on Day 113
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Abatacept Pharmacokinetic (PK) Parameters - Maximum Concentration (Cmax)
大体时间:At the end of infusion and 2 to 4 hours after the start of the infusion on Day 85, at anytime between Day 92 and 96, and pre-dose on Day 113
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Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg.
Maximum Concentration (Cmax)= the maximum plasma concentration of the drug.
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At the end of infusion and 2 to 4 hours after the start of the infusion on Day 85, at anytime between Day 92 and 96, and pre-dose on Day 113
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Abatacept Pharmacokinetic (PK) Parameters - Area Under the Curve (AUC)
大体时间:At the end of infusion, 2 to 4 hours after the start of infusion on Day 85, anytime between Day 92 and 96, and predose on Day 113
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Area Under the Plasma Concentration-Time Curve (AUC), a measure of drug absorption, in a dosing interval of 28 days from Day 85 to Day 113.
Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg.
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At the end of infusion, 2 to 4 hours after the start of infusion on Day 85, anytime between Day 92 and 96, and predose on Day 113
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Abatacept Pharmacokinetic (PK) Parameters: Total Body Clearance (CLT)
大体时间:Day 29, every 28 days until Day 141
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Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg.
Clearance is a pharmacokinetic parameter that describes how quickly drugs are eliminated, metabolized or distributed throughout the body.
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Day 29, every 28 days until Day 141
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Abatacept Pharmacokinetic (PK) Parameters: Volume at Steady State (VSS)
大体时间:At the end of infusion, 2 to 4 hours after the start of infusion on Day 85, anytime between Day 92 and 96, and predose on Day 113
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The volume of distribution of drug at steady state (VSS).
Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg.
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At the end of infusion, 2 to 4 hours after the start of infusion on Day 85, anytime between Day 92 and 96, and predose on Day 113
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Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept
大体时间:At the end of infusion and 2 to 4 hours after the start of the infusion on Day 85
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Minimum concentration (Cmin) of Abatacept 500 mg and 750 mg at given time points
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At the end of infusion and 2 to 4 hours after the start of the infusion on Day 85
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Immunogenicity of Abatacept- Number of Participants With Reactivity Toward CTLA4-IG and CTLA4-T at Day 169
大体时间:Day 169
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Immunogenicity was determined by measuring adult subject sera for reactivity against the whole Abatacept molecule (CTLA4Ig) and CTLA4-T (CTLA4 without the Ig regions).
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Day 169
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Change From Baseline in Surrogate Marker Erythrocyte Sedimentation Rate (ESR) at Day 169
大体时间:From Baseline to Day 169
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Mean change in surrogate marker mean ESR.
A surrogate marker is an indirect measurement of effectiveness.
Change from Baseline = postbaseline - baseline value.
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From Baseline to Day 169
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Change From Baseline in Surrogate Marker Rheumatoid Factor (RF) at Day 169
大体时间:Baseline, Day 169
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Mean change in RF.
A surrogate marker is an indirect measurement of effectiveness.
Mean change from Baseline = postbaseline - baseline value.
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Baseline, Day 169
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LTE Period: Overall Number of Participants With Positive Results of Immunogenicity Samples
大体时间:Days 169, at 6-month intervals on-treatment, and at Days 28, 56, and 85 after the last infusion of study medication in the LTE period
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Positive antibody titers were identified by validated enzyme-linked immunosorbent assay results.
On-treatment samples were obtained during the LTE period, and posttreatment samples were following the last infusion of study medication.
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Days 169, at 6-month intervals on-treatment, and at Days 28, 56, and 85 after the last infusion of study medication in the LTE period
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Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time
大体时间:Days 15 through 1569
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The ACR 20, ACR50, and ACR70 are based on 20%, 50% and 70% improvement, respectively, (compared with baseline values) in tender and swollen joint counts and on 20%, 50% and 70%, respectively, improvement in 3 of the remaining 5 core set measures (participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function) and 1 acute phase reactant value.
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Days 15 through 1569
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Percentage of Participants With Physical Function Response as Assessed Using the Health Assessment Questionnaire Disability Index (HAQ-DI)
大体时间:At Day 1485
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Improvement is measured by an improved response of at least 0.3 units from baseline on the HAQ-DI score.
The HAQ-DI assesses a patient's level of functional ability via 20 questions in 8 categories of functioning.
Patients respond on a scale from 0 (no disability) to 3 (completely disabled); total possible score=24.
Higher score indicates greater disability.
Change from baseline= postbaseline - baseline value.
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At Day 1485
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Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score
大体时间:Day 1485
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The HAQ-DI assesses a patient's level of functional ability via 20 questions in 8 categories of functioning.
Patients respond on a scale from 0 (no disability) to 3 (completely disabled); total possible score=24.
Higher score indicates greater disability.
Change from baseline= postbaseline - baseline value.
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Day 1485
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Changes From Baseline in Short-Form 36 (SF-36) Physical and Mental Health Summaries
大体时间:At Day 1485
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The SF-36 is a 36-item questionnaire used to measure Quality of Life over 8 physically and emotionally based areas: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health.
Answers to each question correspond to a precoded numeric value.
An aggregate percentage score is reached for each of the 8 sections and is based on answers to questions.
The mean average is worked out for each section.
Scores range from 0% (lowest level of functioning) to 100% (highest level of functioning, with higher score indicated increasing levels of functioning.
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At Day 1485
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Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and With EULAR-defined Remission
大体时间:At Days 169 and 1485
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EULAR defines LDAS as a disease activity score as measured by c-reactive protein (DAS28-CRP) ≤3.2 and remission as DAS28-CRP <2.6
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At Days 169 and 1485
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Changes From Baseline in the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) Scores
大体时间:At Days 169 and 1569
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The SDAI is the sum of 5 parameters: Tender joint (TJC) and swollen joint(SJC)counts, based on a 28-joint assessment; patient global (PtGA)and physician global assessments (PGA), assessed on 0-10 cm visual analog scale (VAS), on which higher scores=greater affection due to disease activity DA); and C-reactive protein level.
SDAI total score=0-86.
SDAI <=3.3 indicates disease remission, >3.4 to 11=low DA, >11 to 26=moderate DA, and >26=high DA.
SJC is assessed at each visit, with no swelling=0, swelling=1.
TJC is assessed through identification of joints painful under pressure or to passive motion at each visit, with no tenderness=0, tenderness=1.
Higher score=greater affection due to DA. CDAI is sum of 4 parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PGA (assessed on 0-10 cm VAS; higher scores=greater affection due to disease activity).
CDAI total score=0-76.
CDAI <=2.8 indicates disease remission, >2.8 to 10=low DA, >10 to 22=moderate DA, and >22=high DA.
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At Days 169 and 1569
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Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission
大体时间:At Days 169, 337, 729, 1149, and 1485
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LDAS is defined as a Disease Activity Score C-reactive protein (DAS28-CRP) level <=3.2.
Remission is defined as a DAS28-CRP level <2.6.
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At Days 169, 337, 729, 1149, and 1485
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Change From Baseline in Levels of C-reactive Protein (CRP)
大体时间:Days 169 to 1569
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Days 169 to 1569
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Change From Baseline in Erythrocyte Sedimentation Rate
大体时间:Days 169 to 1569
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Days 169 to 1569
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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
2007年4月1日
初级完成 (实际的)
2008年7月1日
研究完成 (实际的)
2011年12月1日
研究注册日期
首次提交
2006年12月8日
首先提交符合 QC 标准的
2006年12月8日
首次发布 (估计)
2006年12月11日
研究记录更新
最后更新发布 (估计)
2013年8月8日
上次提交的符合 QC 标准的更新
2013年8月6日
最后验证
2013年8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.
Abatacept的临床试验
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University of California, Los AngelesBristol-Myers Squibb终止
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Universitaire Ziekenhuizen KU LeuvenZiekenhuis Netwerk Antwerpen (ZNA)完全的