Abatacept Versus Adalimumab Head-to-Head
3 de enero de 2014 actualizado por: 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
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
869
Fase
- Fase 3
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Cordoba, Argentina, 5000
- Local Institution
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San Juan, Argentina, 5400
- Local Institution
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Tucuman, Argentina, 4000
- Local Institution
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Buenos Aires
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Ciudad Autonoma, Buenos Aires, Argentina, CP1425A WC
- Local Institution
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Ciudad Autonoma De Beunos Aire, Buenos Aires, Argentina, 1431
- Local Institution
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Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentina, 1015
- Local Institution
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Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentina, C1428DQG
- Local Institution
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Quilmes, Buenos Aires, Argentina, 1878
- Local Institution
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Cordoba
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Cordoba, Crd, Cordoba, Argentina, X5016KEH
- Local Institution
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Santa Fe
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Rosario, Santa Fe, Argentina, 2000
- Local Institution
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Tucuman
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San Miguel De Tucuman, Tucuman, Argentina, 4000
- Local Institution
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Quebec, Canadá, G1V 3M7
- Local Institution
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Manitoba
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Winnipeg, Manitoba, Canadá, R3A 1M3
- Local Institution
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Ontario
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Hamilton, Ontario, Canadá, L8N 1Y2
- Local Institution
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Quebec
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Trois-Rivieres, Quebec, Canadá, G8Z 1Y2
- Local Institution
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Providencia
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Santiago, Providencia, Chile
- Local Institution
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Alabama
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Birmingham, Alabama, Estados Unidos, 35294
- University of Alabama at Birmingham
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Birmingham, Alabama, Estados Unidos, 35205
- Rheumatology Associates, Pc
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Tuscaloosa, Alabama, Estados Unidos, 35406
- Clinical and Translational Research Center of Alabama, PC
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Arizona
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Peoria, Arizona, Estados Unidos, 85381
- Sun Valley Arthritis Center, Ltd.
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Arkansas
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Hot Springs, Arkansas, Estados Unidos, 71913
- Mercy Clinic Hot Springs Communities
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California
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Huntington Beach, California, Estados Unidos, 92646
- Talbert Medical Group
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La Jolla, California, Estados Unidos, 92037
- Allergy & Rheumatology Medical Clinic, Inc.
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Long Beach, California, Estados Unidos, 90806
- Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.
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Pasadena, California, Estados Unidos, 91107
- Irene Y. Tong
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San Diego, California, Estados Unidos, 92108
- San Diego Arthritis Medical Clinic
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Torrance, California, Estados Unidos, 90503
- Healthcare Partners Medical Group
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Torrance, California, Estados Unidos, 90505
- Drs. Goldin, Nies, Klashman & Eng
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Upland, California, Estados Unidos, 91786
- Inland Rheumatology & Osteoporosis Medical Group
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Florida
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Aventura, Florida, Estados Unidos, 33180
- Arthritis and Rheumatic Disease Specialties
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Gainesville, Florida, Estados Unidos, 32610
- University Of Florida College Of Medicine At Jacksonville
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Miami, Florida, Estados Unidos, 33173
- Center for Arthritis and Rheumatic Diseases
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Palm Harbor, Florida, Estados Unidos, 34684
- Arthritis Research Of Florida, Inc.
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Sarasota, Florida, Estados Unidos, 34239
- Sarasota Arthritis Research Center
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South Miami, Florida, Estados Unidos, 33143
- Miami Research Associates
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Tamarac, Florida, Estados Unidos, 33321
- West Broward Rheumatology Associates
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Venice, Florida, Estados Unidos, 34292
- Lovelace Scientific Resources, Inc
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Georgia
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Atlanta, Georgia, Estados Unidos, 30342
- Arthritis & Rheumatology of Georgia
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Atlanta, Georgia, Estados Unidos, 30342
- Laureate Clinical Research Group
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Gainesville, Georgia, Estados Unidos, 30501
- Arthritis Center of North Georgia
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Idaho
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Boise, Idaho, Estados Unidos, 83702
- St. Luke's Clinic - Rheumatology
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Coeur D Alene, Idaho, Estados Unidos, 83814
- Coeur D'Alene Arthrit Clin
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Illinois
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Quincy, Illinois, Estados Unidos, 62301
- Quincy Medical Group
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Rockford, Illinois, Estados Unidos, 61107
- Rockford Orthopedic Associates, Ltd.
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Iowa
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Cedar Rapids, Iowa, Estados Unidos, 52401
- Physicians Clinic of Iowa
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Kentucky
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Elizabethtown, Kentucky, Estados Unidos, 42701
- Center For Arthritis and Osteoporosis
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Lexington, Kentucky, Estados Unidos, 40504
- Bluegrass Community Research, Inc.
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Maryland
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Cumberland, Maryland, Estados Unidos, 21502
- Klein And Associates, M.D., Pa
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Wheaton, Maryland, Estados Unidos, 20902
- The Center For Rheumatology And Bone Research
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02115
- Brigham and Women's Hospital
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Mansfield, Massachusetts, Estados Unidos, 02048
- Mansfield Health Center
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Michigan
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Battle Creek, Michigan, Estados Unidos, 49015
- Associated Internal Medicine Specialists
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Kalamazoo, Michigan, Estados Unidos, 49009
- Rheumatology Pc
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Mississippi
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Jackson, Mississippi, Estados Unidos, 39202
- Arthritis Associates Of Mississippi
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Missouri
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St.Louis, Missouri, Estados Unidos, 63131
- Physician Groups, Lc Dba
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Nevada
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Reno, Nevada, Estados Unidos, 89502
- Arthritis Center of Reno
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New Hampshire
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Dover, New Hampshire, Estados Unidos, 03820
- Seacoast Arthritis And Osteoporosis Center
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Nashua, New Hampshire, Estados Unidos, 03060
- Nashua Rheumatology
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New Mexico
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Las Cruces, New Mexico, Estados Unidos, 88011
- Arthritis and Osteoporosis Associates of New Mexico
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New York
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Lake Success, New York, Estados Unidos, 11042
- North Shore Lij Health System
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Mineola, New York, Estados Unidos, 11501
- Winthrop University Hospital
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Smithtown, New York, Estados Unidos, 11787
- Rheumatology Associates of Long Island
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North Carolina
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Asheville, North Carolina, Estados Unidos, 28803
- Asheville Rheumatology & Osteoporosis Research Asso P. A.
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Statesville, North Carolina, Estados Unidos, 28625
- Carolina Pharmaceutical Research
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Oklahoma
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Oklahoma City, Oklahoma, Estados Unidos, 73109
- Health Research Institute
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Oklahoma City, Oklahoma, Estados Unidos, 73103
- Health Research of Oklahoma
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Oklahoma City, Oklahoma, Estados Unidos, 73112
- Lynn Health Sciences Institute
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Pennsylvania
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Bethlehem, Pennsylvania, Estados Unidos, 18015
- East Penn Rheumatology Associates, P.C.
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Duncansville, Pennsylvania, Estados Unidos, 16635
- Altoona Center for Clinical Research
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Wyomissing, Pennsylvania, Estados Unidos, 19610
- Clinical Research Center of Reading, LLP
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South Carolina
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Charleston, South Carolina, Estados Unidos, 29406
- Low Country Rheumatology, PA
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Columbia, South Carolina, Estados Unidos, 29204
- Columbia Arthritis Center, P.A.
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Texas
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Austin, Texas, Estados Unidos, 78758
- Lovelace Scientific Resources, Inc.
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Dallas, Texas, Estados Unidos, 75246
- Arthritis Centers Of Texas
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Houston, Texas, Estados Unidos, 77004
- Rheumatic Disease Clinical Research Center, LLC
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Virginia
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Chesapeake, Virginia, Estados Unidos, 23320
- Center For Arthritis & Rheumatic Diseases, Pc
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Washington
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Spokane, Washington, Estados Unidos, 99202
- Rockwood Research Center
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West Virginia
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Clarksburg, West Virginia, Estados Unidos, 26301
- Mountain State Clinical Research
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Wisconsin
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Glendale, Wisconsin, Estados Unidos, 53217
- Rheumatic Disease Center
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Lima, Perú
- Local Institution
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Lima, Perú, LIMA 11
- Local Institution
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Lima, Perú, LIMA 33
- Local Institution
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Lima, Perú, LIMA 27
- Local Institution
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Callao 2
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Bellavista, Callao 2, Perú
- Local Institution
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Único
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Comparador activo: Adalimumab
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Syringes, Subcutaneous, 40 mg, Biweekly Subcutaneous injections, 24 months (729 days)
Otros nombres:
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Comparador activo: Abatacept
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Syringes, Subcutaneous, 125 mg/syringe for Subcutaneous, Weekly Subcutaneous injections, 24 months (729 days)
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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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
Periodo de tiempo: Day 1 to Day 365
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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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Proportion of Participants With Local Injection Site Reactions Adverse Events (Pre-specified) Reported During 12 Month Period - ITT Population
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: Baseline to Day 729
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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
Periodo de tiempo: 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
Periodo de tiempo: Day 1 to Day 729
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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
Periodo de tiempo: Day 1 to Day 729
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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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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- 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.
Enlaces Útiles
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de octubre de 2009
Finalización primaria (Actual)
1 de octubre de 2011
Finalización del estudio (Actual)
1 de noviembre de 2012
Fechas de registro del estudio
Enviado por primera vez
29 de junio de 2009
Primero enviado que cumplió con los criterios de control de calidad
29 de junio de 2009
Publicado por primera vez (Estimar)
30 de junio de 2009
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
4 de febrero de 2014
Última actualización enviada que cumplió con los criterios de control de calidad
3 de enero de 2014
Última verificación
1 de enero de 2014
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades del sistema inmunológico
- Enfermedades autoinmunes
- Enfermedades Articulares
- Enfermedades musculoesqueléticas
- Enfermedades reumáticas
- Enfermedades del tejido conectivo
- Artritis
- Artritis Reumatoide
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antiinflamatorios
- Agentes antirreumáticos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Inhibidores de puntos de control inmunitarios
- Adalimumab
- Abatacept
Otros números de identificación del estudio
- IM101-235
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .