Abatacept Versus Adalimumab Head-to-Head
2014年1月3日 更新者：Bristol-Myers Squibb
A Randomized, Head-to-Head, Single-Blind Study to Compare the Efficacy and Safety of Subcutaneous Abatacept Versus Subcutaneous Adalimumab, Both With Background Methotrexate, in Biologic-Naive Subjects With Rheumatoid Arthritis
The purpose of this study is demonstrate that subcutaneous abatacept is non-inferior (no worse than) to subcutaneous adalimumab in the treatment of subjects with rheumatoid arthritis who are biologic naive
調査の概要
研究の種類
介入
入学 (実際)
869
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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Alabama
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Birmingham、Alabama、アメリカ、35294
- University of Alabama at Birmingham
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Birmingham、Alabama、アメリカ、35205
- Rheumatology Associates, Pc
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Tuscaloosa、Alabama、アメリカ、35406
- Clinical and Translational Research Center of Alabama, PC
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Arizona
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Peoria、Arizona、アメリカ、85381
- Sun Valley Arthritis Center, Ltd.
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Arkansas
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Hot Springs、Arkansas、アメリカ、71913
- Mercy Clinic Hot Springs Communities
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California
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Huntington Beach、California、アメリカ、92646
- Talbert Medical Group
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La Jolla、California、アメリカ、92037
- Allergy & Rheumatology Medical Clinic, Inc.
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Long Beach、California、アメリカ、90806
- Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.
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Pasadena、California、アメリカ、91107
- Irene Y. Tong
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San Diego、California、アメリカ、92108
- San Diego Arthritis Medical Clinic
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Torrance、California、アメリカ、90503
- Healthcare Partners Medical Group
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Torrance、California、アメリカ、90505
- Drs. Goldin, Nies, Klashman & Eng
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Upland、California、アメリカ、91786
- Inland Rheumatology & Osteoporosis Medical Group
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Florida
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Aventura、Florida、アメリカ、33180
- Arthritis and Rheumatic Disease Specialties
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Gainesville、Florida、アメリカ、32610
- University Of Florida College Of Medicine At Jacksonville
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Miami、Florida、アメリカ、33173
- Center for Arthritis and Rheumatic Diseases
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Palm Harbor、Florida、アメリカ、34684
- Arthritis Research Of Florida, Inc.
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Sarasota、Florida、アメリカ、34239
- Sarasota Arthritis Research Center
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South Miami、Florida、アメリカ、33143
- Miami Research Associates
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Tamarac、Florida、アメリカ、33321
- West Broward Rheumatology Associates
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Venice、Florida、アメリカ、34292
- Lovelace Scientific Resources, Inc
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Georgia
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Atlanta、Georgia、アメリカ、30342
- Arthritis & Rheumatology of Georgia
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Atlanta、Georgia、アメリカ、30342
- Laureate Clinical Research Group
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Gainesville、Georgia、アメリカ、30501
- Arthritis Center of North Georgia
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Idaho
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Boise、Idaho、アメリカ、83702
- St. Luke's Clinic - Rheumatology
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Coeur D Alene、Idaho、アメリカ、83814
- Coeur D'Alene Arthrit Clin
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Illinois
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Quincy、Illinois、アメリカ、62301
- Quincy Medical Group
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Rockford、Illinois、アメリカ、61107
- Rockford Orthopedic Associates, Ltd.
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Iowa
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Cedar Rapids、Iowa、アメリカ、52401
- Physicians Clinic of Iowa
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Kentucky
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Elizabethtown、Kentucky、アメリカ、42701
- Center For Arthritis and Osteoporosis
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Lexington、Kentucky、アメリカ、40504
- Bluegrass Community Research, Inc.
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Maryland
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Cumberland、Maryland、アメリカ、21502
- Klein And Associates, M.D., Pa
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Wheaton、Maryland、アメリカ、20902
- The Center For Rheumatology And Bone Research
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Massachusetts
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Boston、Massachusetts、アメリカ、02115
- Brigham and Women's Hospital
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Mansfield、Massachusetts、アメリカ、02048
- Mansfield Health Center
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Michigan
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Battle Creek、Michigan、アメリカ、49015
- Associated Internal Medicine Specialists
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Kalamazoo、Michigan、アメリカ、49009
- Rheumatology Pc
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Mississippi
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Jackson、Mississippi、アメリカ、39202
- Arthritis Associates Of Mississippi
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Missouri
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St.Louis、Missouri、アメリカ、63131
- Physician Groups, Lc Dba
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Nevada
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Reno、Nevada、アメリカ、89502
- Arthritis Center of Reno
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New Hampshire
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Dover、New Hampshire、アメリカ、03820
- Seacoast Arthritis And Osteoporosis Center
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Nashua、New Hampshire、アメリカ、03060
- Nashua Rheumatology
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New Mexico
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Las Cruces、New Mexico、アメリカ、88011
- Arthritis and Osteoporosis Associates of New Mexico
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New York
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Lake Success、New York、アメリカ、11042
- North Shore Lij Health System
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Mineola、New York、アメリカ、11501
- Winthrop University Hospital
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Smithtown、New York、アメリカ、11787
- Rheumatology Associates of Long Island
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North Carolina
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Asheville、North Carolina、アメリカ、28803
- Asheville Rheumatology & Osteoporosis Research Asso P. A.
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Statesville、North Carolina、アメリカ、28625
- Carolina Pharmaceutical Research
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Oklahoma
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Oklahoma City、Oklahoma、アメリカ、73109
- Health Research Institute
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Oklahoma City、Oklahoma、アメリカ、73103
- Health Research of Oklahoma
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Oklahoma City、Oklahoma、アメリカ、73112
- Lynn Health Sciences Institute
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Pennsylvania
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Bethlehem、Pennsylvania、アメリカ、18015
- East Penn Rheumatology Associates, P.C.
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Duncansville、Pennsylvania、アメリカ、16635
- Altoona Center for Clinical Research
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Wyomissing、Pennsylvania、アメリカ、19610
- Clinical Research Center of Reading, LLP
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South Carolina
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Charleston、South Carolina、アメリカ、29406
- Low Country Rheumatology, PA
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Columbia、South Carolina、アメリカ、29204
- Columbia Arthritis Center, P.A.
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Texas
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Austin、Texas、アメリカ、78758
- Lovelace Scientific Resources, Inc.
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Dallas、Texas、アメリカ、75246
- Arthritis Centers Of Texas
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Houston、Texas、アメリカ、77004
- Rheumatic Disease Clinical Research Center, LLC
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Virginia
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Chesapeake、Virginia、アメリカ、23320
- Center For Arthritis & Rheumatic Diseases, Pc
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Washington
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Spokane、Washington、アメリカ、99202
- Rockwood Research Center
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West Virginia
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Clarksburg、West Virginia、アメリカ、26301
- Mountain State Clinical Research
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Wisconsin
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Glendale、Wisconsin、アメリカ、53217
- Rheumatic Disease Center
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Cordoba、アルゼンチン、5000
- Local Institution
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San Juan、アルゼンチン、5400
- Local Institution
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Tucuman、アルゼンチン、4000
- Local Institution
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Buenos Aires
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Ciudad Autonoma、Buenos Aires、アルゼンチン、CP1425A WC
- Local Institution
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Ciudad Autonoma De Beunos Aire、Buenos Aires、アルゼンチン、1431
- Local Institution
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Ciudad Autonoma De Buenos Aire、Buenos Aires、アルゼンチン、1015
- Local Institution
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Ciudad Autonoma De Buenos Aire、Buenos Aires、アルゼンチン、C1428DQG
- Local Institution
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Quilmes、Buenos Aires、アルゼンチン、1878
- Local Institution
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Cordoba
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Cordoba, Crd、Cordoba、アルゼンチン、X5016KEH
- Local Institution
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Santa Fe
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Rosario、Santa Fe、アルゼンチン、2000
- Local Institution
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Tucuman
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San Miguel De Tucuman、Tucuman、アルゼンチン、4000
- Local Institution
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Quebec、カナダ、G1V 3M7
- Local Institution
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Manitoba
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Winnipeg、Manitoba、カナダ、R3A 1M3
- Local Institution
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Ontario
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Hamilton、Ontario、カナダ、L8N 1Y2
- Local Institution
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Quebec
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Trois-Rivieres、Quebec、カナダ、G8Z 1Y2
- Local Institution
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Providencia
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Santiago、Providencia、チリ
- Local Institution
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Lima、ペルー
- Local Institution
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Lima、ペルー、LIMA 11
- Local Institution
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Lima、ペルー、LIMA 33
- Local Institution
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Lima、ペルー、LIMA 27
- Local Institution
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Callao 2
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Bellavista、Callao 2、ペルー
- Local Institution
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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:
- Moderate to severe Rheumatoid arthritis (RA) according to American College of Rheumatology (ACR) criteria
- Methotrexate failure
- Naive to RA biologics
- ≤5 years duration of disease
- Disease Activity Score-28 C-reactive protein (DAS28 CRP) ≥ 3.2
- Willingness to self-inject subcutaneous (SC) drug
Exclusion Criteria:
- Previous or current medical conditions that are warnings against the use of tumor necrosis factor (TNF)-blocking agents
- History of active or chronic hepatitis
- Cancer in the last 5 years
- History of severe chronic or recurrent bacterial or viral infections
- Risk of tuberculosis
- Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, Gastro-intestinal, pulmonary, cardiac, neurologic, or cerebral 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：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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アクティブコンパレータ：アダリムマブ
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Syringes, Subcutaneous, 40 mg, Biweekly Subcutaneous injections, 24 months (729 days)
他の名前：
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アクティブコンパレータ：Abatacept
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Syringes, Subcutaneous, 125 mg/syringe for Subcutaneous, Weekly Subcutaneous injections, 24 months (729 days)
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 |
|---|---|---|
|
The Proportion of Participants Meeting the American College of Rheumatology (ACR) Criteria of 20% Improvement (ACR20) After 12 Months of Treatment - Intent to Treat Population
時間枠：Day 1 to Day 365
|
Proportion(%)=number of participants meeting criteria (n) divided by number of participants who received drug (N).
The ACR score indicates degree of improvement in a patient's rheumatoid arthritis (RA), based on guidelines set forth by the ACR and represents a percentage.
To qualify a ACR20 score, patient must have >=20% fewer tender joints and >=20% fewer swollen joints and show 20% improvement from baseline in at least 3 of: patient overall assessment of his/her RA, physician global assessment of the patient's RA, patient self-assessment of pain, patient self-assessment of physical functioning, and results of an erythrocyte sedimentation rate or C-reactive protein (CRP) test (to assess inflammation).
Baseline was Day 1. Randomization was stratified using screening Disease Activity Score-28 (DAS28) CRP, a composite of 4 variables: number of tender joints/28, number of swollen joints/28, CRP in mg/L and participant assessment of disease activity with visual analogue scale.
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Day 1 to Day 365
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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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Proportion of Participants With Local Injection Site Reactions Adverse Events (Pre-specified) Reported During 12 Month Period - ITT Population
時間枠：Day 1 to 12 Months
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n=number of participants with a pre-specified local injection site reaction event, N=number of participants at risk.
Proportion (%) = n/N.
12 Months includes data up to 56 days post last dose of the first 12 months Period or start of the first dose of second 12 months period.
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Day 1 to 12 Months
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Incidence Rate of Local Injection Site Reactions (Pre-specified) Reported During 24 Month Period - ITT Population
時間枠：Day 1 to Day 729
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Incidence Rate: (incidence/100 person-years) = number of participants with event * 100 /exposure (person-years) Exposure (person-years) = the sum over all participants of the exposure per participant in the 24 months (censored at the time of first occurrence of AE) expressed in days, divided by 365.25.
The 24 Month Period includes data up to 56 days post the last dose in the 24 month period.
Poisson distribution used to construct the 95% CIs.
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Day 1 to Day 729
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Proportion of Participants Without Radiographic Progression in Total Score Less Than or Equal to the Smallest Detectable Change (SDC) From Baseline to Months 12 and 24 Using Modified Van Der Heijde Total Sharp Score (mSvdHS) - ITT Population
時間枠：Baseline to Day 729
|
Plain radiographs of hands and feet taken at baseline (BL), Day 365, and Day 729.
BL and Day 365 radiographs were re-read concurrent with Day 729 films by readers blinded to sequence and treatment (a second pre-specified reading campaign).
SDC defined as amount of change for which anything smaller could not be reliably distinguished from random error in measurement of simultaneously read films.
Non-progression defined: change from BL (Day 1, prior to dosing) in total score less than, equal to (<=) SDC(2.2).
Proportion n/m (%)=number meeting criteria (n); number analyzed (m).
SDC calculated as SD/sqrt(2)*1.96/sqrt(2)with
standard deviation (SD) of paired differences of change from BL in total score between 2 readers; squared root(sqrt).
mSvdHS=summary of erosion severity in 32 hand and 12 foot joints.
Hand joints scored 0 to 5; foot joints 0 to 10 with 0=no erosion and higher numbers indicating greater erosion severity.
BL: radiographic data within 14 days or less of first dose.
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Baseline to Day 729
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Incidence Rate of Serious Adverse Events (SAEs), Serious Infections, Pre-specified Opportunistic Infections, and Discontinuation for Any Cause at 12 Months of Treatment - ITT Population
時間枠：Day 1 to Day 365
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Pre-specified opportunistic infections include: pneumonia, tuberculosis, herpes zoster, combined opportunistic infections, all hospitalized infections.
Incidence Rate: incidence/100 person-years: numerator was number of unique events within this period (up to 56 days post-last dose of first 12 months or start of first dose of second 12 months); denominator was overall total exposure (person-years) within this period, calculated as sum over all participants of exposure (in days) divided by 365.25.
The resulting incidence rate was multiplied by 100 to express rate per 100 person-years.
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE is a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
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Day 1 to Day 365
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Incidence Rate of Serious Adverse Events (SAEs), Serious Infections, Pre-specified Opportunistic Infections, and Discontinuation for Any Cause at 24 Months of Treatment - ITT Population
時間枠：Day 1 to Day 729
|
Pre-specified opportunistic infections include: pneumonia, tuberculosis, herpes zoster, combined opportunistic infections, and all hospitalized infections.
Incidence Rate: incidence/100 person-years: numerator was number of unique events within this period (up to 56 days post the last dose of the 24 Months period); denominator was overall total exposure (person-years) within this period, which was calculated as the sum over all participants of exposure (in days) divided by 365.25.
The resulting incidence rate was multiplied by 100 to express the rate per 100 person-years.
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE is a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
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Day 1 to Day 729
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Proportion of Participants With Induction of Autoantibodies During the 12 Months and 24 Months Periods - ITT Population
時間枠：Day 1 to Day 729
|
The induction of autoantibodies was defined as participant's antinuclear antibodies (ANA) or anti-double stranded deoxyribonucleic acid (dsDNA) converting from a negative status at baseline to a positive status at a post-baseline measurement time point (Day 365 or Day 729).
Proportion (%) = n/m, where n=number of participants with positive ANA or dsDNA at a time point and m=number of participants who had negative ANA or dsDNA at baseline.
Blood samples were first tested for ANA by indirect fluorescent assay using HEp-2 Cell Line Substrate, and when positive, samples were further tested for anti-dsDNA by indirect fluorescent assay using Crithidia Luciliae Substrate.
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Day 1 to Day 729
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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
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
- Keystone EC, Ahmad HA, Yazici Y, Bergman MJ. Disease activity measures at baseline predict structural damage progression: data from the randomized, controlled AMPLE and AVERT trials. Rheumatology (Oxford). 2020 Aug 1;59(8):2090-2098. doi: 10.1093/rheumatology/kez455.
- Jabado O, Maldonado MA, Schiff M, Weinblatt ME, Fleischmann R, Robinson WH, He A, Patel V, Greenfield A, Saini J, Galbraith D, Connolly SE. Differential Changes in ACPA Fine Specificity and Gene Expression in a Randomized Trial of Abatacept and Adalimumab in Rheumatoid Arthritis. Rheumatol Ther. 2022 Apr;9(2):391-409. doi: 10.1007/s40744-021-00404-x. Epub 2021 Dec 8.
- Fleischmann R, Weinblatt M, Ahmad H, Maldonado MA, Alemao E, Ye J, Schiff M. Efficacy of Abatacept and Adalimumab in Patients with Early Rheumatoid Arthritis With Multiple Poor Prognostic Factors: Post Hoc Analysis of a Randomized Controlled Clinical Trial (AMPLE). Rheumatol Ther. 2019 Dec;6(4):559-571. doi: 10.1007/s40744-019-00174-7. Epub 2019 Oct 22.
- Fleischmann R, Connolly SE, Maldonado MA, Schiff M. Brief Report: Estimating Disease Activity Using Multi-Biomarker Disease Activity Scores in Rheumatoid Arthritis Patients Treated With Abatacept or Adalimumab. Arthritis Rheumatol. 2016 Sep;68(9):2083-9. doi: 10.1002/art.39714.
- Schiff M, Weinblatt ME, Valente R, Citera G, Maldonado M, Massarotti E, Yazici Y, Fleischmann R. Reductions in disease activity in the AMPLE trial: clinical response by baseline disease duration. RMD Open. 2016 Apr 19;2(1):e000210. doi: 10.1136/rmdopen-2015-000210. eCollection 2016.
- Fleischmann R, Weinblatt ME, Schiff M, Khanna D, Maldonado MA, Nadkarni A, Furst DE. Patient-Reported Outcomes From a Two-Year Head-to-Head Comparison of Subcutaneous Abatacept and Adalimumab for Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2016 Jul;68(7):907-13. doi: 10.1002/acr.22763.
- Sokolove J, Schiff M, Fleischmann R, Weinblatt ME, Connolly SE, Johnsen A, Zhu J, Maldonado MA, Patel S, Robinson WH. Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial. Ann Rheum Dis. 2016 Apr;75(4):709-14. doi: 10.1136/annrheumdis-2015-207942. Epub 2015 Sep 10.
- Schiff M, Weinblatt ME, Valente R, van der Heijde D, Citera G, Elegbe A, Maldonado M, Fleischmann R. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial. Ann Rheum Dis. 2014 Jan;73(1):86-94. doi: 10.1136/annrheumdis-2013-203843. Epub 2013 Aug 20.
- Weinblatt ME, Schiff M, Valente R, van der Heijde D, Citera G, Zhao C, Maldonado M, Fleischmann R. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum. 2013 Jan;65(1):28-38. doi: 10.1002/art.37711.
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10月1日
一次修了 (実際)
2011年10月1日
研究の完了 (実際)
2012年11月1日
試験登録日
最初に提出
2009年6月29日
QC基準を満たした最初の提出物
2009年6月29日
最初の投稿 (見積もり)
2009年6月30日
学習記録の更新
投稿された最後の更新 (見積もり)
2014年2月4日
QC基準を満たした最後の更新が送信されました
2014年1月3日
最終確認日
2014年1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。