A Long-Term Extension Study of WA22762 to Evaluate Safety and Efficacy of Subcutaneous Tocilizumab in Participants With Moderate to Severe Rheumatoid Arthritis (RA).
2016年10月5日 更新者：Hoffmann-La Roche
A Multicenter, Open-Label Long-Term Extension Study of WA22762 to Evaluate Safety and Efficacy of Subcutaneous Tocilizumab in Patients With Moderate to Severe Rheumatoid Arthritis
This multicenter, open-label, single arm, interventional, long-term extension (LTE) study will evaluate the safety and efficacy of tocilizumab (TCZ, RoActemra/Actemra) in French participants with moderate to severe RA who have completed the Week 97 visit of WA22762 LTE study (NCT01194414) (EudraCT Number 2010-018375-22).
Participants from France, who completed the Week 97 visit of the WA22762 LTE study and considered as responders (defined as having improvement in disease activity score based on 28-joint count [DAS28] of greater than [>] 1.2 points) will continue TCZ treatment within this local LTE study for a maximum of 156 weeks of subcutaneous (SC) TCZ treatment, or until SC TCZ becomes commercially available, whichever occurs first.
調査の概要
研究の種類
介入
入学 (実際)
11
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Bordeaux、フランス、33076
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Montpellier、フランス、34295
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Nantes、フランス、44035
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Paris、フランス、75679
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Strasbourg、フランス、67098
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Toulouse、フランス、31059
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Negative pregnancy test at screening and baseline
- Participants who have completed the 97-week WA22762 LTE study on SC or intravenous (IV) TCZ and who experienced, at any time during WA22762, clinically significant improvement in DAS28 (>1.2 points), and based on the investigator's judgment may continue to benefit from TCZ treatment in this study investigating the SC formulation
- No current or recent adverse events or laboratory findings preventing the use of the study drug dose of TCZ 162 mg SC at baseline visit
- Receiving treatment on an outpatient basis
- Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception during the study and for at least 3 months following the last dose of study drug
- Oral corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDS) up to the recommended dose are permitted if on stable dose regimen for greater than and equal to (>/=) 4 weeks prior to baseline
- Permitted non-biological disease-modifying anti-rheumatic drugs (DMARDs) are allowed
Exclusion Criteria:
- Participants who have prematurely withdrawn from the WA22762 LTE study for any reason
- Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies
- Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL) 1 agent, or a T-cell co stimulation modulator since the last administration of study drug in the WA22762 LTE study
- Immunization with a live/attenuated vaccine since the last administration of study drug in the WA22762 LTE study
- Diagnosis, since last WA22762 visit (Week 97), of rheumatic autoimmune disease other than rheumatoid arthritis; secondary Sjörgen's syndrome with RA is permitted
- Diagnosis, since last WA22762 visit (Week 97), of inflammatory joint disease other than RA
- Uncontrolled disease states, such as asthma or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids
- Evidence of serious uncontrolled concomitant disease
- Known active current or history of recurrent infection
- Primary or secondary immunodeficiency (history of or currently active)
- Body weight >150 kilograms (kg)
- Pregnant or lactating women
- Inadequate hematologic, renal or liver function
- History of alcohol, drug or chemical abuse within 1 year prior to screening
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：Tocilizumab
Moderate to severe rheumatoid arthritis participants from France, who completed the Week 97 visit of the WA22762 LTE study and considered as responders (defined as having improvement in DAS28 of >1.2 points) will continue tocilizumab treatment within this local LTE study for a maximum of 156 weeks, or until SC TCZ becomes commercially available, whichever occurs first.
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Participants will receive TCZ 162 milligrams (mg) SC injection once a week.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
時間枠：Baseline up to approximately 142 weeks
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An adverse event (AE) was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment.
An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment.
A SAE was any untoward medical occurrence that at any dose resulted in death, was life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity, and congenital anomaly/birth defect.
AEs included SAEs as well as non-serious AEs.
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Baseline up to approximately 142 weeks
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Percentage of Participants With AEs and SAEs Related to TCZ
時間枠：Baseline up to approximately 142 weeks
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An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
AEs included SAEs as well as non-serious AEs.
Causality of AEs based on physician's discretion: certain (AE after drug intake, not explained by other drugs, reaction on drug cessation [DC], relapse on re-intake of drug), probable/likely (AE after drug intake, not explained by other drugs, reaction on DC, no information on re-intake), possible (AE after drug intake, explained by other drugs, no information on DC), unlikely (not related to drug intake time, explained by other drugs).
AEs with causality of certain, probable/likely, and possible were considered TCZ related.
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Baseline up to approximately 142 weeks
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Percentage of Participants With Adverse Events of Special Interest (AESIs)
時間枠：Baseline up to approximately 142 weeks
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Adverse events of special interest (AESI) for this study included: infections (including opportunistic infections), myocardial infarction/acute coronary syndrome, gastrointestinal perforation and related events, malignancies, anaphylaxis / hypersensitivity reactions, demyelinating disorders, stroke, bleeding events and hepatic events.
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Baseline up to approximately 142 weeks
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Percentage of Participants With AESIs Related to TCZ
時間枠：Baseline up to approximately 142 weeks
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AESI for this study included: infections (including opportunistic infections), myocardial infarction/acute coronary syndrome, gastrointestinal perforation and related events, malignancies, anaphylaxis / hypersensitivity reactions, demyelinating disorders, stroke, bleeding events and hepatic events.
Percentage of participants with AESI related to the drug were presented.
Causality of AESIs based on physician's discretion: certain (AE after drug intake, not explained by other drugs, reaction on DC, relapse on re-intake of drug), probable/likely (AE after drug intake, not explained by other drugs, reaction on DC, no information on re-intake), possible (AE after drug intake, explained by other drugs, no information on DC), unlikely (not related to drug intake time, explained by other drugs).
AESIs with causality of certain, probable/likely, and possible were considered TCZ related.
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Baseline up to approximately 142 weeks
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Percentage of Participants With AEs Leading to TCZ Discontinuation, Interruption, or Dose Modification
時間枠：Baseline up to approximately 142 weeks
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An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug.
Percentage of participants with AE causing drug discontinuation, interruption and increase or decrease in dose of drug was presented.
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Baseline up to approximately 142 weeks
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Percentage of Participants With Clinically Significant Physical Examinations and Vital Signs Abnormalities
時間枠：Baseline up to approximately 142 weeks
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Criteria for potentially clinically important (PCI) change in vital signs: heart rate value of less than (<) 40 beats per minute and value greater than (>) 150 beats per minute, systolic blood pressure (SBP) of < 80 or >210 millimeter of mercury (mmHg), diastolic blood pressure (DBP) of <40 or >130 mmHg, body temperature <32 or > 40 degrees Celsius, respiratory rate of <10 or > 50 breaths/minute and criteria for PCI change in physical examination: >/=10% increase or decrease of body weight in kilograms (kg).
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Baseline up to approximately 142 weeks
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Percentage of Participants With Clinically Significant Laboratory Abnormalities
時間枠：Baseline up to approximately 142 weeks
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Criteria for laboratory tests clinically significant abnormalities included: hemoglobin, hematocrit and red blood cells (RBCs)(< 0.8*lower limit of normal[LLN]); leucocytes (<0.6/greater than [>]1.5*upper
limit of normal [ULN]); platelets (<0.5*LLN></0>1.75*ULN);
neutrophils, lymphocytes (<0.8*LLN></0>1.2*ULN);
eosinophils, basophils, monocytes (>1.2*ULN); total bilirubin, direct bilirubin, indirect bilirubin (>1.5*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (>3*ULN), total protein, albumin (<0.8*LLN></0>1.2*ULN);
creatinine, urea (>1.3*ULN); glucose (<0.6*LLN></0>1.5*ULN);
uric acid (>1.2*ULN); sodium, potassium, chloride, calcium, bicarbonate (<0.9*LLN></0>1.1*ULN);
urine RBCs, urine white blood cells (WBCs) (> or equal[=]20 high-powered field), urine bacteria >20 high-powered field.
Overall percentage of participants with any clinically significant laboratory abnormality was reported.
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Baseline up to approximately 142 weeks
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Percentage of Participants With Anti-TCZ Antibodies
時間枠：Baseline up to approximately 142 weeks
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Baseline up to approximately 142 weeks
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score
時間枠：Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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The DAS 28 ESR score is a measure of the participant's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment (PtGA) of disease activity (visual analog scale [VAS]: 0 millimeter [mm] = no disease activity to 100 mm=maximum disease activity) and the erythrocyte sedimentation rate (ESR in millimeters per hour [mm/hr]).
DAS28 was calculated using following formulas: DAS28-ESR = 0.56*square root (sqrt) (TJC28) + 0.28*sqrt (SJC28) + 0.70*natural logarithm (ln) (ESR) + 0.014*PtGA of disease activity.
A total possible score of 0 to approximately 10, with higher score indicating more severe disease activity.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in Simplified Disease Activity Index (SDAI) Score
時間枠：Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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The SDAI was calculated as (SJC [28 joints] + TJC [28 joints] + VAS ptGA + VAS physician global assessment of disease activity + C-reactive Protein (CRP) level in milligram/deciliter [mg/dL]).
VAS assessments: 0 centimeters (cm)=no disease activity to 10 cm=maximum disease activity.
SDAI score ranged from 0 to 86, with higher scores indicating increased disease activity.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in TJC
時間枠：Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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For TJC a total of 28 joints were assessed.
The presence of a tender joint was scored as 1 and absence as 0. Total score is calculated by adding the scores, which is ranging from 0 (best possible score or no tender joint) to 28 (worse possible score or all tender joints).
Lower scores indicate no tender joint and higher scores indicate worsening tender joints.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in SJC
時間枠：Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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For SJC, a total of 28 joints were assessed.
The presence of a swollen joint was scored as 1 and absence as 0. Total score is calculated by adding the scores, which is ranging from 0 (best possible score or no swollen joint) to 28 (worse possible score or all swollen joints).
Lower scores indicate no swollen joint and higher scores indicate worsening swollen joints.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Percentage of Participants With Clinical Remission
時間枠：Week 48, 108
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Clinical remission defined as:DAS28-ESR score < 2.6 and/or SDAI score </= 3.3.DAS28 score is measure of subject's disease activity calculated using TJC [28 joints],SJC [28 joints],PtGA of disease activity [ VAS:0mm= no disease activity to 100 mm=maximum disease activity] and ESR (mm/hr).
DAS28 was calculated as DAS28-ESR = 0.56*sqrt (TJC28) + 0.28*sqrt(SJC28) + 0.70* ln ESR + 0.014*PtGA of disease activity.
DAS28-ESR score ranged from 0 to approximately 10, higher score indicating more severe disease activity.
SDAI was calculated =[SJC (28 joints) + TJC (28 joints) + VAS PtGA + VAS physician global assessment of disease activity+CRP level(mg/dL)].
VAS assessments:0 mm=no disease activity to 100 mm=maximum disease activity.
SDAI score ranged from 0 to 86, with higher scores indicating increased disease activity.
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Week 48, 108
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Percentage of Participants With Concomitant Corticosteroid Discontinuation
時間枠：Baseline up to approximately 142 weeks
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Baseline up to approximately 142 weeks
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Percentage of Participants With Concomitant Corticosteroid Dose Reduction
時間枠：Baseline up to approximately 142 weeks
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Baseline up to approximately 142 weeks
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Time to Concomitant Corticosteroid Discontinuation
時間枠：Baseline up to approximately 142 weeks
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Time to corticosteroid discontinuation = (End date of corticosteroid treatment - date of first drug intake of this extension study) + 1.
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Baseline up to approximately 142 weeks
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Time to Concomitant Corticosteroid Dose Reduction
時間枠：Baseline up to approximately 142 weeks
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Time to corticosteroid dose reduction (days) = (Date of the first dose reduction of corticosteroid treatment - date of first drug intake of this extension study) + 1.
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Baseline up to approximately 142 weeks
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Change From Baseline in PtGA of Disease Activity
時間枠：Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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PtGA of disease activity over the previous 24 hours using a 100 mm VAS where left end of the line 0 mm =no disease activity and right end of the line 100 mm =maximum disease activity.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in Patient's Assessment of Pain
時間枠：Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Patient's assessment of pain over the previous 24 hours: using a VAS, left end of the line 0 mm=no pain to right end of the line 100 mm=unbearable pain.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score
時間枠：Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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The HAQ-DI questionnaire measures functional status (disability) and health-related quality of life.
It measures the participant's ability to perform everyday tasks.
The index consists of 20 questions regarding the function of the upper and lower extremities.
These questions are summarized in 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common activities over past week.
Each question is evaluated according to the degree of severity on a 4-point scale.
Total score for HAQ-DI was the average of all questions and ranges from 0 = without any difficulty to 3 = unable to do.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in Physician's Global Assessment of Disease Activity
時間枠：Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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The Physician's Global Assessment of disease activity was assessed using a 0 to 100 mm horizontal VAS.
The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity".
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in ESR
時間枠：Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Blood samples were collected for ESR, which is an acute phase reactant and provides a non-specific measure of inflammation.
The test assesses the rate at which red blood cells fall in a test tube.
Normal range is 0-30 millimeters per hour (mm/hr).
A decrease in the level indicates reduction in inflammation and therefore improvement.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in CRP
時間枠：Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Blood samples were collected for CRP, which is an acute phase reactant and a measure of inflammation.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2012年10月1日
一次修了 (実際)
2015年9月1日
研究の完了 (実際)
2015年9月1日
試験登録日
最初に提出
2012年11月19日
QC基準を満たした最初の提出物
2012年11月27日
最初の投稿 (見積もり)
2012年11月28日
学習記録の更新
投稿された最後の更新 (見積もり)
2016年11月28日
QC基準を満たした最後の更新が送信されました
2016年10月5日
最終確認日
2016年10月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。