A Study of Tocilizumab and Methotrexate Treatment Strategies (Adding Tocilizumab to Methotrexate Versus Switching to Tocilizumab) in Patients With Active Rheumatoid Arthritis With Inadequate Response to Prior Methotrexate Treatment
2014年7月16日 更新者：Hoffmann-La Roche
Randomized Placebo-controlled Study of Two Treatment Strategies Based on Tocilizumab (TCZ) With or Without Methotrexate (MTX) and Possible Addition of Other Disease-modifying Anti-rheumatic Drugs (DMARDs) in Patients...
This 2 arm study will compare 2 treatment strategies based on tocilizumab in combination with methotrexate or placebo in patients with moderate to severe rheumatoid arthritis.
Patients receiving methotrexate treatment will be randomized to receive either a) tocilizumab 8 mg intravenous (iv) every 4 weeks + methotrexate orally (po) weekly or b) tocilizumab 8 mg iv every 4 weeks + placebo po weekly.
After the first 24 weeks of blinded treatment, treatment adjustments (increase or decrease of treatment intensity) may be introduced at intervals, based on response.
The anticipated time on study treatment is up to 3 years, and the target sample size is approximately 470 patients.
調査の概要
研究の種類
介入
入学 (実際)
556
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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California
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Santa Monica、California、アメリカ、90404
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Upland、California、アメリカ、91786
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Whittier、California、アメリカ、90606
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Florida
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Aventura、Florida、アメリカ、33180
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Naples、Florida、アメリカ、34102
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Orange Park、Florida、アメリカ、32073
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Plantation、Florida、アメリカ、33317
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Sarasota、Florida、アメリカ、34239
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South Miami、Florida、アメリカ、33143
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Tamarac、Florida、アメリカ、33321
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Minnesota
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Eagan、Minnesota、アメリカ、55121
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Nevada
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Las Vegas、Nevada、アメリカ、89128
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Ohio
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Mayfield、Ohio、アメリカ、44143
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Middleburg Heights、Ohio、アメリカ、44130
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Oklahoma
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Oklahoma City、Oklahoma、アメリカ、73104
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Pennsylvania
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West Reading、Pennsylvania、アメリカ、19611
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South Carolina
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Greenville、South Carolina、アメリカ、29601
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Tennessee
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Nashville、Tennessee、アメリカ、37205
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Texas
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Houston、Texas、アメリカ、77004
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San Antonio、Texas、アメリカ、78217
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Washington
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Spokane、Washington、アメリカ、99204
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Cannock、イギリス、WS11 5XY
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Glasgow、イギリス、G12 0YN
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Leeds、イギリス、LS7 4SA
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London、イギリス、SE5 9RS
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Newcastle-upon-Tyne、イギリス、NE2 4HH
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Norwich、イギリス、NR4 7UY
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Afula、イスラエル、18101
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Beer Sheva、イスラエル、8410101
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Haifa、イスラエル、31048
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Haifa、イスラエル、34362
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Haifa、イスラエル、34354
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Kfar Saba、イスラエル、44281
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Ramat-Gan、イスラエル、52621
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Rishon Lezion、イスラエル
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Tel Aviv、イスラエル、6423906
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Ancona、イタリア、60020
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Bari、イタリア、70124
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Perugia、イタリア、06122
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Prato、イタリア、59100
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Roma、イタリア、00168
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Tallinn、エストニア、11312
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Tallinn、エストニア、13419
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Amsterdam、オランダ、1105 AZ
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Amsterdam、オランダ、1081 HV
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Leiden、オランダ、2333 ZA
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Maastricht、オランダ、6202 AZ
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Nijmegen、オランダ、6525 GA
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Utrecht、オランダ、3584 CX
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Athens、ギリシャ、11527
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Thessaloniki、ギリシャ、54642
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Thessaloniki、ギリシャ、54636
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Rijeka、クロアチア、51000
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Zagreb、クロアチア、10000
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Goeteborg、スウェーデン、41345
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Umea、スウェーデン、90185
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Barcelona、スペイン、08003
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Madrid、スペイン、28046
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Madrid、スペイン、28041
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Madrid、スペイン、28007
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Madrid、スペイン、28222
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Sevilla、スペイン、41009
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Asturias
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Oviedo、Asturias、スペイン、33006
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La Coruña
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La Coruna、La Coruña、スペイン、15006
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Santiago De Compostela、La Coruña、スペイン、15706
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Madrid
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Leganes、Madrid、スペイン、28191
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Vizcaya
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Bilbao、Vizcaya、スペイン、48013
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Belgrade、セルビア、11000
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Kragujevac、セルビア、34000
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Niska Banja、セルビア、18250
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Nova sad、セルビア、21000
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Bangkok、タイ、10300
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Khon Kaen、タイ、40002
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Pathumthani、タイ、12120
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Frederiksberg、デンマーク、2000
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Hellerup、デンマーク、2900
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Køge、デンマーク、4600
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Aachen、ドイツ、52064
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Berlin、ドイツ、10117
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Berlin、ドイツ、13125
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Dresden、ドイツ、01307
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Erlangen、ドイツ、91054
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Hamburg、ドイツ、22081
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Jena、ドイツ、07747
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Köln、ドイツ、50924
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Muenchen、ドイツ、80336
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Ratingen、ドイツ、40882
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Wuerzburg、ドイツ、97080
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Drammen、ノルウェー、3004
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Gjettum、ノルウェー、1346
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Kristiansand、ノルウェー、4604
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Lillehammer、ノルウェー、2609
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Moss、ノルウェー、1535
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Oslo、ノルウェー、0319
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Abbeville、フランス、80142
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Boulogne-billancourt、フランス、92104
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Brest、フランス、29609
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Echirolles、フランス、38434
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Le Kremlin Bicetre、フランス、94275
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Le Mans、フランス、72037
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Marseille、フランス、13285
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Marseille、フランス、13385
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Monaco、フランス、98012
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Nantes、フランス、44035
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Nice、フランス、06202
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Paris、フランス、75571
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Paris、フランス、75679
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Pierre Benite、フランス、69495
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Vandoeuvre-les-nancy、フランス、54511
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MG
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Belo Horizonte、MG、ブラジル、30130-100
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RS
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Porto Alegre、RS、ブラジル、90035-903
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SP
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Sao Paulo、SP、ブラジル、05403-000
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Sao Paulo、SP、ブラジル、04026-000
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Sao Paulo、SP、ブラジル、04039-004
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Bauska、ラトビア、3901
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Daugavpils、ラトビア、5417
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Liepaja、ラトビア、3400
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Riga、ラトビア、LV-1002
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Riga、ラトビア、1038
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Riga、ラトビア、1006
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Bucharest、ルーマニア、011172
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Bucuresti、ルーマニア、020983
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Barnaul、ロシア連邦、656024
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Ekaterinburg、ロシア連邦、620102
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Irkutsk、ロシア連邦、664047
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Izhevsk、ロシア連邦、426009
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Kazan、ロシア連邦、420012
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Khanty-Mansiysk、ロシア連邦、628011
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Kursk、ロシア連邦、305007
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Moscow、ロシア連邦、115522
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Novosibirsk、ロシア連邦、630117
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Novosibirsk、ロシア連邦、630099
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St Petersburg、ロシア連邦、191015
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Tjumen、ロシア連邦、625023
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UFA、ロシア連邦、450005
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Ulyanovsk、ロシア連邦、432063
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Vladivostok、ロシア連邦、690105
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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:
- adult patients, ≥ 18 years of age;
- moderate to severe active rheumatoid arthritis (Disease Activity Score (DAS28) > 4.4);
- inadequate response to methotrexate;
- on a stable dose of ≥ 15mg/week methotrexate for at least 6 weeks.
Exclusion Criteria:
- prior treatment with a biologic;
- Rheumatoid arthritis (RA) functional class IV;
- known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections;
- evidence of active malignant disease.
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：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
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 + Methotrexate
Tocilizumab 8 mg/kg (up to 800 mg) intravenous (IV) once every 4 weeks + weekly oral methotrexate continuing at the patient's pre-study dose for 24 weeks.
Patients taking oral corticosteroids remained on their pre-study dose (up to 10 mg/day).
Week 24 to Week 52 the dose of tocilizumab and methotrexate remained the same.
Based on DAS28 assessments, corticosteroid dose was adjusted and disease-modifying antirheumatic drugs (DMARDS) added.
Week 52 to Week 104, based on the DAS28 assessment, treatment was adjusted to one of four protocol specified treatment regimens: Treatment tapering, Continued treatment, Treatment intensification or Maintenance treatment.
After Week 100, patients who discontinued tocilizumab because of remission were retreated with the last effective dose of tocilizumab or blinded methotrexate if a flare occurred.
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tocilizumab 8 mg IV every 4 weeks.
他の名前：
Approximately 15-17 mg methotrexate capsule orally once a week.
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プラセボコンパレーター：Tocilizumab + Placebo
Tocilizumab 8 mg/kg (up to 800 mg) IV once every 4 weeks + weekly oral placebo to methotrexate continuing at the patient's pre-study dose for 24 weeks.
Patients taking oral corticosteroids remained on their pre-study dose (up to 10 mg/day).
Week 24 to Week 52 the dose of tocilizumab and placebo to methotrexate remained the same.
Based on DAS28 assessments, corticosteroid dose was adjusted and disease-modifying antirheumatic drug (DMARDS) added.
Week 52 to Week 104, based on the DAS28 assessment, treatment was adjusted to one of four protocol specified treatment regimens: Treatment tapering, Continued treatment, Treatment intensification or Maintenance treatment.
After Week 100, patients who discontinued tocilizumab because of remission were retreated with the last effective dose of tocilizumab or blinded placebo to methotrexate if a flare occurred.
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tocilizumab 8 mg IV every 4 weeks.
他の名前：
Placebo matching methotrexate capsule taken orally once a week.
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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 Disease Activity Score 28 Joints (DAS28) Remission at Week 24
時間枠：Week 24
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The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control.
DAS28 Remission is defined as a DAS28 score < 2.6.
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Week 24
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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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Percentage of Participants With American College of Rheumatology (ACR20) Response
時間枠：Baseline, Weeks 24, 52, 104
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ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
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Baseline, Weeks 24, 52, 104
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Percentage of Participants With ACR50 Response
時間枠：Baseline, Weeks 24, 52, 104
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ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
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Baseline, Weeks 24, 52, 104
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Percentage of Participants With ACR70 Response
時間枠：Baseline, Weeks 24, 52, 104
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ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
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Baseline, Weeks 24, 52, 104
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Percentage of Participants With ACR90 Response
時間枠：Baseline, Weeks 24, 52, 104
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ACR90 response is defined as a ≥ 90% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
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Baseline, Weeks 24, 52, 104
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Time to First ACR20 Response
時間枠：104 Weeks
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Time in days from first administration of study drug until ACR20 response.
ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
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104 Weeks
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Time to First ACR50 Response
時間枠：104 Weeks
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Time in days from first administration of study drug until ACR50 response.
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate).
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104 Weeks
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Time to First ACR70 Response
時間枠：104 Weeks
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Time in days from first administration of study drug until ACR70 response.
ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
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104 Weeks
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Time to First ACR90 Response
時間枠：104 Weeks
|
Time in days from first administration of study drug until ACR90 response.
ACR90 response is defined as a ≥ 90% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
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104 Weeks
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Area Under Curve (AUC) DAS28
時間枠：Baseline to Week 24
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The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control.
AUC DAS28 was averaged over study days.
Analysis of Covariance was adjusted for Baseline DAS28 as a covariate and treatment group and region as fixed factors.
Higher calculated AUC values are worse (indicate higher disease activity).
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Baseline to Week 24
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Percentage of Participants With Disease Activity Score 28 (DAS28) Remission
時間枠：Week 52
|
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control.
DAS28 Remission is defined as a DAS28 score < 2.6.
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Week 52
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Percentage of Participants With DAS28 Low Disease Activity (LDAS)
時間枠：Weeks 24, 52
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The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control.
LDAS is defined as DAS28 ≤ 3.2.
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Weeks 24, 52
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Change From Baseline in DAS28 Score
時間枠：Baseline, Weeks 24, 52
|
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control.
A higher value indicated higher disease activity.
A negative change from Baseline indicated improvement.
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Baseline, Weeks 24, 52
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Percentage of Participants With Good or Moderate European League (EULAR) DAS28 Responses
時間枠：Baseline, 24, 52
|
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 or a change from Baseline < -1.2. EULAR Moderate response: DAS28 > 3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2. |
Baseline, 24, 52
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Change From Baseline in Swollen Joint Count
時間枠：Baseline, Weeks 24, 52
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66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66.
A negative change from Baseline indicated improvement.
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Baseline, Weeks 24, 52
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Change From Baseline in Tender Joint Count
時間枠：Baseline, Weeks 24, 52
|
68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68.
A negative change from Baseline indicated improvement.
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Baseline, Weeks 24, 52
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Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (VAS)
時間枠：Baseline, Weeks 24, 52
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The patients global assessment of disease activity was assessed on a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS) by the patient.
The left-hand extreme of the line equals 0 mm, and was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity).
A negative change from Baseline indicated improvement.
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Baseline, Weeks 24, 52
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Change From Baseline in Physician Global Assessment of Disease Activity Visual Analog Scale (VAS)
時間枠：Baseline, Weeks 24, 52
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The physician global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician.
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" (maximum arthritis disease activity).
A negative change from Baseline indicated improvement.
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Baseline, Weeks 24, 52
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Change From Baseline in Patient Global Assessment of Pain (VAS)
時間枠：Baseline, Weeks 24, 52
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The patient assessed their pain using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS).
The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain".
A negative change from Baseline indicated improvement.
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Baseline, Weeks 24, 52
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Change From Baseline in Erythrocyte Sedimentation Rate (ESR)
時間枠：Baseline, Weeks 24, 52
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Blood was collected for Erythrocyte Sedimentation Rate (ESR) (a test that assesses tissue inflammation) and was analyzed at a local laboratory.
ESR was measured in millimeters/hour (mm/hr).
A reduction in the level is considered an improvement.
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Baseline, Weeks 24, 52
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Change From Baseline in C-Reactive Protein (CRP)
時間枠：Baseline, Weeks 24, 52
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Blood was collected for C-Reactive Protein (CRP) (a test for analysis of inflammatory and infectious disorders) and was analyzed at a central laboratory.
The serum concentration of CRP was measured in milligrams/deciliter (mg/dL).
A reduction in the level is considered an improvement.
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Baseline, Weeks 24, 52
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Change From Baseline in the Health Assessment Questionnaire Disability Index
時間枠：Baseline, Weeks 24, 52
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The Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis, consisting of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities.
There are 4 possible responses for each question: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do.
The score for each of the domains is the highest (worst) score in each domain.
A patient must have a domain score for at least 6 of 8 domains to calculate a valid HAQ-DI score which is the sum of domain scores, divided by the number of domains that have a score for a total possible score minimum/maximum 0 (best) to 3 (worst).
A negative change from Baseline indicated improvement.
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Baseline, Weeks 24, 52
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Change From Baseline in Total Genant Modified Sharp Scores (GSS)
時間枠：Baseline, Weeks 24, 52, 104
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Radiographs were taken of each hand and foot at Baseline, Weeks 24, 52 and104 and were evaluated using the Genant modified method according to Sharp.
Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion.
Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint).
The maximum total erosion score in the hands is 98 and in the feet 42.
The maximum scores for joint space narrowing (JSN) in the hands was104 and in the feet 48.
The total score was the sum of scores for erosions and JSN.
The maximum total modified GSS was 292.
A lower number change from Baseline was better.
Analysis of covariance model, with Baseline DAS28 as a covariate and treatment and site as fixed factors.
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Baseline, Weeks 24, 52, 104
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Change From Baseline in Joint Space Narrowing Score
時間枠：Baseline, Weeks 24, 52, 104
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A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint).
The maximum scores for joint space narrowing (JSN) in the hands was 104 and in the feet 48 for a total possible score of 0 to 152.
A lower change from Baseline indicated a better score.
Analysis of covariance model included baseline x-ray and DAS28 as covariates and treatment group and region as fixed effects.
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Baseline, Weeks 24, 52, 104
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Change From Baseline in Erosion Score
時間枠：Baseline, Weeks 24, 52, 104
|
A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion.
The maximum erosion score in the hands was 98 and in the feet 42 for a total possible score of 0 to 140.
A lower number change from Baseline indicated a better score.
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Baseline, Weeks 24, 52, 104
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Percentage of Participants Discontinuing Tocilizumab Due to Remission
時間枠：Weeks 52, 104
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The percentage of participants who stopped treatment with tocilizumab due to remission.
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Weeks 52, 104
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Percentage of Participants Who Withdrew Due to Lack of Sufficient Therapeutic Response
時間枠：Up to 3 years
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Lack of Sufficient Therapeutic Response was defined as the patient not responding to the drug as expected.
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Up to 3 years
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Percentage of Participants Who Withdrew Due to Safety Reasons
時間枠：Up to 3 years
|
Safety reasons were defined as adverse events, intercurrent illness or death.
An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug.
Preexisting conditions that worsened during the study were reported as adverse events.
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Up to 3 years
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Change From Baseline in Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL)
時間枠：Baseline, Weeks 24, 52, 104
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The RAQoL is a disease specific patient-reported outcome measure that determines the effect rheumatoid arthritis has on a patient's quality of life consisting of 30 questions that are answered either yes=1 or no=0 for a total possible score ranging from 0 (best) to 30 (worst).
A negative change from Baseline indicated improvement.
|
Baseline, Weeks 24, 52, 104
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Change From Baseline in Academic Medical Center (AMC) Linear Disability Scale (ALDS)
時間枠：Baseline, Weeks 104
|
The Academic Medical Center (AMC) Linear Disability Score (ALDS) evaluates the participant's ability to perform activities of daily life consisting of 77 questions answered yes or no .
The question difficulty and the patient's ability are arranged on a single hierarchical linear scale.
ALDS scores range from 10 to 90 with a higher score representing higher functional status.
A positive change from Baseline indicated improvement.
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Baseline, Weeks 104
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Area Under the Curve (AUC) From Baseline to Week 24 for ACR Response
時間枠：Baseline to Week 24
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ACR response was defined as an improvement (reduction) compared with baseline for both total joint count-68 joints and swollen joint count-66 joints, and for three of five variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) where 0=no pain to 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where: 0=no disease activity to 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
Area under the curve for ACR response to Week 24 was averaged over study days.
Analysis of covariance model includes treatment group, region and baseline DAS28 (≤ 5.5 and > 5.5) as fixed factors.
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Baseline to Week 24
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|
Area Under the Curve (AUC) From Baseline to Week 52 for ACR Response
時間枠：Baseline to Week 52
|
ACR response was defined as an improvement (reduction) compared with baseline for both total joint count-68 joints and swollen joint count-66 joints, and for three of five variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) where 0=no pain to 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where: 0=no disease activity to 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].Area under the curve for ACR response to Week 52 averaged over study days.
Analysis of covariance model includes treatment group, region and baseline DAS28 (<=5.5 and >5.5) as fixed factors.
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Baseline to Week 52
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|
Time to Tocilizumab Remission
時間枠：104 Weeks
|
The time in days from initial study drug treatment to tocilizumab remission that occurred when the patient discontinued treatment with tocilizumab.
|
104 Weeks
|
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Time to Drug-Free Remission
時間枠：104 Weeks
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The time in days from initial study drug treatment to drug free remission that occurred when the participant was able to discontinue tocilizumab, methotrexate/placebo and open label disease-modifying antirheumatic drugs (DMARDS).
|
104 Weeks
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Time to Flare After Tocilizumab Remission
時間枠：104 Weeks
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The time in days to a flare (recurrence of disease symptoms) after the patient discontinued treatment with tocilizumab.
|
104 Weeks
|
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Time to Restart of Treatment After Discontinuation/Remission
時間枠：104 Weeks
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The time in days from treatment discontinuation or remission to the restart of treatment.
|
104 Weeks
|
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
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Dougados M, Kissel K, Sheeran T, Tak PP, Conaghan PG, Mola EM, Schett G, Amital H, Navarro-Sarabia F, Hou A, Bernasconi C, Huizinga TW. Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis. 2013 Jan;72(1):43-50. doi: 10.1136/annrheumdis-2011-201282. Epub 2012 May 5.
- Dougados M, Kissel K, Conaghan PG, Mola EM, Schett G, Gerli R, Hansen MS, Amital H, Xavier RM, Troum O, Bernasconi C, Huizinga TW. Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study. Ann Rheum Dis. 2014 May;73(5):803-9. doi: 10.1136/annrheumdis-2013-204761. Epub 2014 Jan 28.
- Dougados M, Huizinga TW, Choy EH, Bingham CO 3rd, Aassi M, Bernasconi C. Evaluation of the Disease Activity Score in Twenty-Eight Joints-Based Flare Definitions in Rheumatoid Arthritis: Data From a Three-Year Clinical Trial. Arthritis Care Res (Hoboken). 2015 Dec;67(12):1762-6. doi: 10.1002/acr.22633.
- Huizinga TW, Conaghan PG, Martin-Mola E, Schett G, Amital H, Xavier RM, Troum O, Aassi M, Bernasconi C, Dougados M. Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study. Ann Rheum Dis. 2015 Jan;74(1):35-43. doi: 10.1136/annrheumdis-2014-205752. Epub 2014 Aug 28.
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
2009年3月1日
一次修了 (実際)
2010年8月1日
研究の完了 (実際)
2013年1月1日
試験登録日
最初に提出
2008年12月16日
QC基準を満たした最初の提出物
2008年12月16日
最初の投稿 (見積もり)
2008年12月17日
学習記録の更新
投稿された最後の更新 (見積もり)
2014年7月18日
QC基準を満たした最後の更新が送信されました
2014年7月16日
最終確認日
2014年7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。
tocilizumab [RoActemra/Actemra]の臨床試験
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