Evaluation of Efficacy and Safety of Fostamatinib Monotherapy Compared With Adalimumab Monotherapy in Patients With Rheumatoid Arthritis (RA) (OSKIRA -4)
2014年4月3日 更新者：AstraZeneca
(OSKIRA-4): A Phase IIB, Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Fostamatinib Disodium Monotherapy Compared With Adalimumab Monotherapy in Patients With Active Rheumatoid Arthritis
The purpose of the study is to evaluate the improvements in signs and symptoms of rheumatoid arthritis (RA) for fostamatinib compared to placebo or adalimumab in patients who are Disease-Modifying anti-rheumatic drug (DMARD) naïve, DMARD intolerant or have had an inadequate response to DMARDs.
The study will last for approximately six months
調査の概要
状態
終了しました
条件
詳細な説明
Sub-study:
Full title: Optional Genetic Research
Date: 10 September 2010
Version: 1
Objectives: To collect and store, with appropriate consent , DNA samples for future exploratory research into genes/genetic variation that may influence response (ie, absorption, distribution, metabolism and excretion, safety, tolerability and efficacy) to fostamatinib disodium and/or adalimumab; and/or susceptibility to, progression of and prognosis of RA
The main study recruitment is complete, and sub study recruitment will continue until the target is reached, estimated to be June 2013
Sub-study:
Full title: (Sub-study to OSKIRA-4): A Phase IIB, Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Fostamatinib Disodium Monotherapy Compared with Placebo or Adalimumab Monotherapy in Patients with Active Rheumatoid Arthritis: Magnetic Resonance Imaging Sub-Study
Date: 21 March 2011
Version: 1
Primary objective: Assess the efficacy of fostamatinib in reducing joint synovial disease activity as measured by:
- Change from baseline to Week 6 (versus placebo) in OMERACT RAMRIS synovitis score.
研究の種類
介入
入学 (実際)
644
段階
- フェーズ2
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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Alabama
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Birmingham、Alabama、アメリカ
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Arizona
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Glendale、Arizona、アメリカ
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Mesa、Arizona、アメリカ
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Phoenix、Arizona、アメリカ
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Scottsdale、Arizona、アメリカ
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California
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Huntington Beach、California、アメリカ
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Long Beach、California、アメリカ
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Colorado
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Colorado Springs、Colorado、アメリカ
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Connecticut
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Bridgeport、Connecticut、アメリカ
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Florida
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Daytona Beach、Florida、アメリカ
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Jacksonville、Florida、アメリカ
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Miami、Florida、アメリカ
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Ocala、Florida、アメリカ
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Palm Harbor、Florida、アメリカ
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Pinellas Park、Florida、アメリカ
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Venice、Florida、アメリカ
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Illinois
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Chicago、Illinois、アメリカ
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Indiana
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South Bend、Indiana、アメリカ
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Kentucky
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Bowling Green、Kentucky、アメリカ
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Elizabethtown、Kentucky、アメリカ
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Maryland
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Oxon Hill、Maryland、アメリカ
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Michigan
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Kalamazoo、Michigan、アメリカ
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Missouri
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Richmond Heights、Missouri、アメリカ
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Montana
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Kalispell、Montana、アメリカ
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New Hampshire
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Nashua、New Hampshire、アメリカ
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New Mexico
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Albuquerque、New Mexico、アメリカ
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Las Cruces、New Mexico、アメリカ
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New York
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Brooklyn、New York、アメリカ
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North Carolina
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Charlotte、North Carolina、アメリカ
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Ohio
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Perrysburg、Ohio、アメリカ
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Pennsylvania
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Duncansville、Pennsylvania、アメリカ
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South Carolina
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Greenville、South Carolina、アメリカ
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Tennessee
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Jackson、Tennessee、アメリカ
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Knoxville、Tennessee、アメリカ
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Memphis、Tennessee、アメリカ
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Texas
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Austin、Texas、アメリカ
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Houston、Texas、アメリカ
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Mesquite、Texas、アメリカ
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Plano、Texas、アメリカ
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San Antonio、Texas、アメリカ
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Basingstoke、イギリス
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Eastbourne、イギリス
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London、イギリス
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Manchester、イギリス
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Wolverhampton、イギリス
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Berkshire
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Reading、Berkshire、イギリス
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Greater London
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London、Greater London、イギリス
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Sussex
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Eastbourne、Sussex、イギリス
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Donetsk、ウクライナ
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Ivano-frankivsk、ウクライナ
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Kharkiv、ウクライナ
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Kyiv、ウクライナ
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Lutsk、ウクライナ
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Lviv、ウクライナ
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Odessa、ウクライナ
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Simferopol、ウクライナ
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Zaporyzhzhya、ウクライナ
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Amsterdam、オランダ
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Ontario
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Mississauga、Ontario、カナダ
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Trebisov、スロバキア
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Trnava、スロバキア
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Brno、チェコ共和国
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Bruntal、チェコ共和国
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Hlucin、チェコ共和国
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Liberec、チェコ共和国
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Ostrava、チェコ共和国
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Ostrava - Poruba、チェコ共和国
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Ostrava - Trebovice、チェコ共和国
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Praha、チェコ共和国
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Praha 11、チェコ共和国
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Praha 2、チェコ共和国
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Praha 4、チェコ共和国
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Zlin、チェコ共和国
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Dresden、ドイツ
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Hamburg、ドイツ
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Muenchen、ドイツ
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Balatonfured、ハンガリー
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Balatonfüred、ハンガリー
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Budapest、ハンガリー
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Debrecen、ハンガリー
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Zalaegerszeg、ハンガリー
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Pleven、ブルガリア
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Plovdiv、ブルガリア
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Ruse、ブルガリア
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Sevlievo、ブルガリア
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Sofia、ブルガリア
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Veliko Tarnovo、ブルガリア
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Bytom、ポーランド
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Chelm Slaski、ポーランド
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Grodzisk Mazowiecki、ポーランド
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Sroda Wielkopolska、ポーランド
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Warszawa、ポーランド
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Wroclaw、ポーランド
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Zyrardow、ポーランド
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Łódź、ポーランド
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Moscow、ロシア連邦
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Nizhny Novgorod、ロシア連邦
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Petrozavodsk、ロシア連邦
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Ryazan、ロシア連邦
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St. Petersburg、ロシア連邦
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Voronezh、ロシア連邦
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Yaroslavl、ロシア連邦
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Cape Town、南アフリカ
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Durban、南アフリカ
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Pretoria、南アフリカ
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Stellenbosch、南アフリカ
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Gauteng
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Pretoria、Gauteng、南アフリカ
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Kwazulu Natal
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Durban、Kwazulu Natal、南アフリカ
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Western Cape
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Cape Town、Western Cape、南アフリカ
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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:
- Male or female aged 18 and over
- Active rheumatoid arthritis (RA) diagnosed after the age of 16 and diagnosis within 5 years prior to study visit 1 and inadequate response to treatment with a maximum 2 Disease-Modifying anti-rheumatic drug (DMARD) therapies, or diagnosis within 5 years prior to study visit 1 and intolerance to DMARD therapy, or diagnosis within 2 years prior to study visit 1 and no previous use of DMARDs
- 4 or more swollen joints and 4 or more tender/painful joints (from 28 joint count) and either Erythrocyte Sedimentation Rate (ESR) blood result of 28mm/h or more, or C-Reactive Protein (CRP) blood result of 10mg/L or more
- At least 2 of the following: documented history or current presence of positive rheumatoid factor (blood test), radiographic erosion within 12 months prior to study enrolment, presence of serum anti-cyclic citrullinated peptide antibodies (blood test)
Exclusion Criteria:
- Females who are pregnant or breast feeding
- Poorly controlled hypertension
- Liver disease or significant liver function test abnormalities
- Certain inflammatory conditions (other than rheumatoid arthritis), connective tissue diseases or chronic pain disorders
- Recent or significant cardiovascular disease
- Significant active or recent infection including tuberculosis
- Previously received treatment with a TNF alpha antagonist (including etanercept, certolizumab, adalimumab, infliximab, golimumab) or anakinra or previous treatment with other biological agent including rituximab, abatacept and tocilizumab
- Use of any DMARDs within 6 weeks before first study visit
- Severe renal impairment
- Neutropenia
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 |
|---|---|
|
実験的：Dosing Group A
Oral treatment and subcutaneous injection
|
Fostamatinib 100mg twice daily and placebo injection once every two weeks
Fostamatinib 100mg twice daily / fostamatinib 150mg once daily and placebo injection once every two weeks
Fostamatinib 100mg twice daily / fostamatinib 100mg once daily and placebo injection once every two weeks.
|
|
実験的：Dosing Group B
Oral treatment and subcutaneous injection
|
Fostamatinib 100mg twice daily and placebo injection once every two weeks
Fostamatinib 100mg twice daily / fostamatinib 150mg once daily and placebo injection once every two weeks
Fostamatinib 100mg twice daily / fostamatinib 100mg once daily and placebo injection once every two weeks.
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実験的：Dosing Group C
Oral treatment and subcutaneous injection
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Fostamatinib 100mg twice daily and placebo injection once every two weeks
Fostamatinib 100mg twice daily / fostamatinib 150mg once daily and placebo injection once every two weeks
Fostamatinib 100mg twice daily / fostamatinib 100mg once daily and placebo injection once every two weeks.
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アクティブコンパレータ：Dosing Group D
Oral treatment and subcutaneous injection
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Adalimumab 40mg injection once every two weeks and placebo to fostamatinib twice daily.
他の名前：
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プラセボコンパレーター：Dosing Group E
Oral treatment and subcutaneous injection
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Placebo injection once every two weeks.
Placebo to fostamatinib for six weeks, followed by fostamatinib 100mg twice daily (Group F) / fostamatinib 100mg twice daily then 150mg once daily (Group G).
|
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 |
|---|---|---|
|
DAS28-CRP Score - Change From Baseline to Week 6 Compared to Placebo
時間枠：Baseline and 6 weeks
|
DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patient's own assessment.
Scores can take any positive value with a lower value indicating a better clinical condition.
Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicative of a better clinical condition.
ANCOVA = analysis of covariance, BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, QD = once a day, SC = subcutaneous.
|
Baseline and 6 weeks
|
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DAS28-CRP Score - Change From Baseline to Week 24 Compared to Adalimumab
時間枠：Baseline and 24 weeks
|
DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patient's own assessment.
Scores can take any positive value with a lower value indicating a better clinical condition.
Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicative of a better clinical condition.
Non-responder imputation has been applied by carrying the baseline observation forward.
ANCOVA = analysis of covariance, BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, QD = once a day, SC = subcutaneous.
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Baseline and 24 weeks
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
DAS28 EULAR Response at Week 6
時間枠：6 weeks
|
Change in DAS28 was derived for each post baseline scheduled assessment and categorised using the European League Against Rheumatism (EULAR) response criteria.
Non-responder imputation has been applied by carrying the baseline observation forward.
bid = twice daily, DAS28 = Disease Activity Score based on a 28-joint count, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, qd = once a day, SC = subcutaneous.
|
6 weeks
|
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DAS28 EULAR Response at Week 24
時間枠：24 weeks
|
Change in DAS28 was derived for each post baseline scheduled assessment and categorised using the European League Against Rheumatism (EULAR) response criteria.
Non-responder imputation has been applied by carrying the baseline observation forward.
bid = twice daily, DAS28 = Disease Activity Score based on a 28-joint count, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, qd = once a day, SC = subcutaneous.
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24 weeks
|
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Proportion of Patients Achieving ACR20 up to Week 24
時間枠：6 and 24 weeks
|
ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function.
Non-responder imputation has been applied by carrying the baseline observation forward.
BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
|
6 and 24 weeks
|
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Proportion of Patients Achieving ACR50 up to Week 24
時間枠：6 and 24 weeks
|
ACR50: American College of Rheumatology 50% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function.
Non-responder imputation has been applied by carrying the baseline observation forward.
BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
|
6 and 24 weeks
|
|
Proportion of Patients Achieving ACR70 up to Week 24
時間枠：6 and 24 weeks
|
ACR70: American College of Rheumatology 70% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function.
Non-responder imputation has been applied by carrying the baseline observation forward.
BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
|
6 and 24 weeks
|
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ACRn - Comparison Between Fostamatinib and Placebo at Week 6
時間枠：Baseline and 6 weeks
|
ACRn: American College of Rheumatology Index of RA improvement, based on smallest percentage improvement in the count of swollen joints (out of 28 joints), count of tender joints (out of 28 joints) or in blood test measures of inflammation (such as CRP) or the physician and patient's own asessment of disease activity, pain and physical function.
Scores are reported as a percentage improvement on a scale of -100 to +100, with larger values representing a better clinical outcome.
Non-responder imputation has been applied by carrying the baseline observation forward.
BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
Mean refers to change at Week 6. Treatment difference: difference between fostamatinib and placebo groups.
|
Baseline and 6 weeks
|
|
ACRn - Comparison Between Fostamatinib and Adalimumab at Week 24
時間枠：Baseline and 24 weeks
|
ACRn: American College of Rheumatology Index of RA improvement, based on smallest percentage improvement in the count of swollen joints (out of 28 joints), count of tender joints (out of 28 joints) or in blood test measures of inflammation (such as CRP) or the physician and patient's own asessment of disease activity, pain and physical function.
Scores are reported as a percentage improvement on a scale of -100 to +100, with larger values representing a better clinical outcome.
Non-responder imputation has been applied by carrying the baseline observation forward.
BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
Mean refers to change at Week 24.
Treatment difference: difference between fostamatinib and adalimumab groups.
|
Baseline and 24 weeks
|
|
HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Placebo at Week 6
時間枠：Baseline and 6 weeks
|
HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function.
The HAQ-DI score is calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygiene, reach, grip and common daily activities) and dividing by the number of categories completed.
The HAQ-DI score takes values between 0 and 3, with a higher score indicating greater disability.
Non-responder imputation has been applied by carrying the baseline observation forward.
ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
|
Baseline and 6 weeks
|
|
HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Adalimumab at Week 24
時間枠：Baseline and 24 weeks
|
HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function.
The HAQ-DI score is calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygiene, reach, grip and common daily activities) and dividing by the number of categories completed.
The HAQ-DI score takes values between 0 and 3, with a higher score indicating greater disability.
Non-responder imputation has been applied by carrying the baseline observation forward.
ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
|
Baseline and 24 weeks
|
|
SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Adalimumab at Week 24
時間枠：Baseline and 24 weeks
|
SF-36: 36-item Short Form Health Survey, a measure of health-related QoL.
Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional & Mental Health) are derived & normalised to a scale of 0-100.
Physical & Mental Component Scores (PCS & MCS) are derived by multiplying each of these 8 scores by a constant, summing them & standardising against a population with mean of 50, standard deviation of 10.
Higher scores represent a better QoL.
Mean changes from baseline score are presented at each visit as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition.
Non-responder imputation applied by carrying the baseline observation forward.
ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, PO = orally, QD = once a day, QoL = quality of life, SC = subcutaneous.
|
Baseline and 24 weeks
|
|
SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Adalimumab at Week 24
時間枠：Baseline and 24 weeks
|
SF-36: 36-item Short Form Health Survey, a measure of health-related QoL.
Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional & Mental Health) are derived & normalised to a scale of 0-100.
Physical & Mental Component Scores (PCS & MCS) are derived by multiplying each of these 8 scores by a constant, summing them & standardising against a population with mean of 50, standard deviation of 10.
Higher scores represent a better QoL.
Mean changes from baseline score are presented at each visit as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition.
Non-responder imputation applied by carrying the baseline observation forward.
ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, PO = orally, QD = once a day, QoL = quality of life, SC = subcutaneous.
|
Baseline and 24 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
捜査官
- スタディディレクター：Neil MacKillop, MD PhD、AstraZeneca
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。
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
2011年1月1日
一次修了 (実際)
2012年10月1日
研究の完了 (実際)
2013年8月1日
試験登録日
最初に提出
2010年12月17日
QC基準を満たした最初の提出物
2010年12月21日
最初の投稿 (見積もり)
2010年12月22日
学習記録の更新
投稿された最後の更新 (見積もり)
2014年5月6日
QC基準を満たした最後の更新が送信されました
2014年4月3日
最終確認日
2014年4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。