Abatacept Versus Adalimumab Head-to-Head
3 janvier 2014 mis à jour par: 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
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
869
Phase
- Phase 3
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Cordoba, Argentine, 5000
- Local Institution
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San Juan, Argentine, 5400
- Local Institution
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Tucuman, Argentine, 4000
- Local Institution
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Buenos Aires
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Ciudad Autonoma, Buenos Aires, Argentine, CP1425A WC
- Local Institution
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Ciudad Autonoma De Beunos Aire, Buenos Aires, Argentine, 1431
- Local Institution
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Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentine, 1015
- Local Institution
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Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentine, C1428DQG
- Local Institution
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Quilmes, Buenos Aires, Argentine, 1878
- Local Institution
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Cordoba
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Cordoba, Crd, Cordoba, Argentine, X5016KEH
- Local Institution
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Santa Fe
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Rosario, Santa Fe, Argentine, 2000
- Local Institution
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Tucuman
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San Miguel De Tucuman, Tucuman, Argentine, 4000
- Local Institution
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Quebec, Canada, G1V 3M7
- Local Institution
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Manitoba
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Winnipeg, Manitoba, Canada, R3A 1M3
- Local Institution
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Ontario
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Hamilton, Ontario, Canada, L8N 1Y2
- Local Institution
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Quebec
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Trois-Rivieres, Quebec, Canada, G8Z 1Y2
- Local Institution
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Providencia
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Santiago, Providencia, Chili
- Local Institution
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Lima, Pérou
- Local Institution
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Lima, Pérou, LIMA 11
- Local Institution
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Lima, Pérou, LIMA 33
- Local Institution
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Lima, Pérou, LIMA 27
- Local Institution
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Callao 2
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Bellavista, Callao 2, Pérou
- Local Institution
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Alabama
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Birmingham, Alabama, États-Unis, 35294
- University of Alabama at Birmingham
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Birmingham, Alabama, États-Unis, 35205
- Rheumatology Associates, Pc
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Tuscaloosa, Alabama, États-Unis, 35406
- Clinical and Translational Research Center of Alabama, PC
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Arizona
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Peoria, Arizona, États-Unis, 85381
- Sun Valley Arthritis Center, Ltd.
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Arkansas
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Hot Springs, Arkansas, États-Unis, 71913
- Mercy Clinic Hot Springs Communities
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California
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Huntington Beach, California, États-Unis, 92646
- Talbert Medical Group
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La Jolla, California, États-Unis, 92037
- Allergy & Rheumatology Medical Clinic, Inc.
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Long Beach, California, États-Unis, 90806
- Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.
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Pasadena, California, États-Unis, 91107
- Irene Y. Tong
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San Diego, California, États-Unis, 92108
- San Diego Arthritis Medical Clinic
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Torrance, California, États-Unis, 90503
- Healthcare Partners Medical Group
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Torrance, California, États-Unis, 90505
- Drs. Goldin, Nies, Klashman & Eng
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Upland, California, États-Unis, 91786
- Inland Rheumatology & Osteoporosis Medical Group
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Florida
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Aventura, Florida, États-Unis, 33180
- Arthritis and Rheumatic Disease Specialties
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Gainesville, Florida, États-Unis, 32610
- University Of Florida College Of Medicine At Jacksonville
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Miami, Florida, États-Unis, 33173
- Center for Arthritis and Rheumatic Diseases
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Palm Harbor, Florida, États-Unis, 34684
- Arthritis Research Of Florida, Inc.
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Sarasota, Florida, États-Unis, 34239
- Sarasota Arthritis Research Center
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South Miami, Florida, États-Unis, 33143
- Miami Research Associates
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Tamarac, Florida, États-Unis, 33321
- West Broward Rheumatology Associates
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Venice, Florida, États-Unis, 34292
- Lovelace Scientific Resources, Inc
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Georgia
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Atlanta, Georgia, États-Unis, 30342
- Arthritis & Rheumatology of Georgia
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Atlanta, Georgia, États-Unis, 30342
- Laureate Clinical Research Group
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Gainesville, Georgia, États-Unis, 30501
- Arthritis Center of North Georgia
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Idaho
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Boise, Idaho, États-Unis, 83702
- St. Luke's Clinic - Rheumatology
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Coeur D Alene, Idaho, États-Unis, 83814
- Coeur D'Alene Arthrit Clin
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Illinois
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Quincy, Illinois, États-Unis, 62301
- Quincy Medical Group
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Rockford, Illinois, États-Unis, 61107
- Rockford Orthopedic Associates, Ltd.
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Iowa
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Cedar Rapids, Iowa, États-Unis, 52401
- Physicians Clinic of Iowa
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Kentucky
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Elizabethtown, Kentucky, États-Unis, 42701
- Center For Arthritis and Osteoporosis
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Lexington, Kentucky, États-Unis, 40504
- Bluegrass Community Research, Inc.
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Maryland
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Cumberland, Maryland, États-Unis, 21502
- Klein And Associates, M.D., Pa
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Wheaton, Maryland, États-Unis, 20902
- The Center For Rheumatology And Bone Research
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Massachusetts
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Boston, Massachusetts, États-Unis, 02115
- Brigham and Women's Hospital
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Mansfield, Massachusetts, États-Unis, 02048
- Mansfield Health Center
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Michigan
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Battle Creek, Michigan, États-Unis, 49015
- Associated Internal Medicine Specialists
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Kalamazoo, Michigan, États-Unis, 49009
- Rheumatology Pc
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Mississippi
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Jackson, Mississippi, États-Unis, 39202
- Arthritis Associates Of Mississippi
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Missouri
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St.Louis, Missouri, États-Unis, 63131
- Physician Groups, Lc Dba
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Nevada
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Reno, Nevada, États-Unis, 89502
- Arthritis Center of Reno
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New Hampshire
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Dover, New Hampshire, États-Unis, 03820
- Seacoast Arthritis And Osteoporosis Center
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Nashua, New Hampshire, États-Unis, 03060
- Nashua Rheumatology
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New Mexico
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Las Cruces, New Mexico, États-Unis, 88011
- Arthritis and Osteoporosis Associates of New Mexico
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New York
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Lake Success, New York, États-Unis, 11042
- North Shore Lij Health System
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Mineola, New York, États-Unis, 11501
- Winthrop University Hospital
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Smithtown, New York, États-Unis, 11787
- Rheumatology Associates of Long Island
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North Carolina
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Asheville, North Carolina, États-Unis, 28803
- Asheville Rheumatology & Osteoporosis Research Asso P. A.
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Statesville, North Carolina, États-Unis, 28625
- Carolina Pharmaceutical Research
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Oklahoma
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Oklahoma City, Oklahoma, États-Unis, 73109
- Health Research Institute
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Oklahoma City, Oklahoma, États-Unis, 73103
- Health Research of Oklahoma
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Oklahoma City, Oklahoma, États-Unis, 73112
- Lynn Health Sciences Institute
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Pennsylvania
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Bethlehem, Pennsylvania, États-Unis, 18015
- East Penn Rheumatology Associates, P.C.
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Duncansville, Pennsylvania, États-Unis, 16635
- Altoona Center for Clinical Research
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Wyomissing, Pennsylvania, États-Unis, 19610
- Clinical Research Center of Reading, LLP
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South Carolina
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Charleston, South Carolina, États-Unis, 29406
- Low Country Rheumatology, PA
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Columbia, South Carolina, États-Unis, 29204
- Columbia Arthritis Center, P.A.
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Texas
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Austin, Texas, États-Unis, 78758
- Lovelace Scientific Resources, Inc.
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Dallas, Texas, États-Unis, 75246
- Arthritis Centers Of Texas
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Houston, Texas, États-Unis, 77004
- Rheumatic Disease Clinical Research Center, LLC
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Virginia
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Chesapeake, Virginia, États-Unis, 23320
- Center For Arthritis & Rheumatic Diseases, Pc
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Washington
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Spokane, Washington, États-Unis, 99202
- Rockwood Research Center
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West Virginia
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Clarksburg, West Virginia, États-Unis, 26301
- Mountain State Clinical Research
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Wisconsin
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Glendale, Wisconsin, États-Unis, 53217
- Rheumatic Disease Center
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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 d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Seul
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Comparateur actif: Adalimumab
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Syringes, Subcutaneous, 40 mg, Biweekly Subcutaneous injections, 24 months (729 days)
Autres noms:
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Comparateur actif: Abatacept
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Syringes, Subcutaneous, 125 mg/syringe for Subcutaneous, Weekly Subcutaneous injections, 24 months (729 days)
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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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
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Proportion of Participants With Local Injection Site Reactions Adverse Events (Pre-specified) Reported During 12 Month Period - ITT Population
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- 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.
Liens utiles
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 octobre 2009
Achèvement primaire (Réel)
1 octobre 2011
Achèvement de l'étude (Réel)
1 novembre 2012
Dates d'inscription aux études
Première soumission
29 juin 2009
Première soumission répondant aux critères de contrôle qualité
29 juin 2009
Première publication (Estimation)
30 juin 2009
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
4 février 2014
Dernière mise à jour soumise répondant aux critères de contrôle qualité
3 janvier 2014
Dernière vérification
1 janvier 2014
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du système immunitaire
- Maladies auto-immunes
- Maladies articulaires
- Maladies musculo-squelettiques
- Maladies rhumatismales
- Maladies du tissu conjonctif
- Arthrite
- Arthrite, rhumatoïde
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-inflammatoires
- Agents antirhumatismaux
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Inhibiteurs de point de contrôle immunitaire
- Adalimumab
- Abatacept
Autres numéros d'identification d'étude
- IM101-235
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .