Abatacept Versus Adalimumab Head-to-Head
3. januar 2014 oppdatert av: 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
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
869
Fase
- Fase 3
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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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, 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, Chile
- Local Institution
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Alabama
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Birmingham, Alabama, Forente stater, 35294
- University of Alabama at Birmingham
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Birmingham, Alabama, Forente stater, 35205
- Rheumatology Associates, Pc
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Tuscaloosa, Alabama, Forente stater, 35406
- Clinical and Translational Research Center of Alabama, PC
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Arizona
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Peoria, Arizona, Forente stater, 85381
- Sun Valley Arthritis Center, Ltd.
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Arkansas
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Hot Springs, Arkansas, Forente stater, 71913
- Mercy Clinic Hot Springs Communities
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California
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Huntington Beach, California, Forente stater, 92646
- Talbert Medical Group
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La Jolla, California, Forente stater, 92037
- Allergy & Rheumatology Medical Clinic, Inc.
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Long Beach, California, Forente stater, 90806
- Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.
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Pasadena, California, Forente stater, 91107
- Irene Y. Tong
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San Diego, California, Forente stater, 92108
- San Diego Arthritis Medical Clinic
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Torrance, California, Forente stater, 90503
- Healthcare Partners Medical Group
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Torrance, California, Forente stater, 90505
- Drs. Goldin, Nies, Klashman & Eng
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Upland, California, Forente stater, 91786
- Inland Rheumatology & Osteoporosis Medical Group
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Florida
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Aventura, Florida, Forente stater, 33180
- Arthritis and Rheumatic Disease Specialties
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Gainesville, Florida, Forente stater, 32610
- University Of Florida College Of Medicine At Jacksonville
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Miami, Florida, Forente stater, 33173
- Center for Arthritis and Rheumatic Diseases
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Palm Harbor, Florida, Forente stater, 34684
- Arthritis Research Of Florida, Inc.
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Sarasota, Florida, Forente stater, 34239
- Sarasota Arthritis Research Center
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South Miami, Florida, Forente stater, 33143
- Miami Research Associates
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Tamarac, Florida, Forente stater, 33321
- West Broward Rheumatology Associates
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Venice, Florida, Forente stater, 34292
- Lovelace Scientific Resources, Inc
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Georgia
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Atlanta, Georgia, Forente stater, 30342
- Arthritis & Rheumatology of Georgia
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Atlanta, Georgia, Forente stater, 30342
- Laureate Clinical Research Group
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Gainesville, Georgia, Forente stater, 30501
- Arthritis Center of North Georgia
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Idaho
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Boise, Idaho, Forente stater, 83702
- St. Luke's Clinic - Rheumatology
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Coeur D Alene, Idaho, Forente stater, 83814
- Coeur D'Alene Arthrit Clin
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Illinois
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Quincy, Illinois, Forente stater, 62301
- Quincy Medical Group
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Rockford, Illinois, Forente stater, 61107
- Rockford Orthopedic Associates, Ltd.
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Iowa
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Cedar Rapids, Iowa, Forente stater, 52401
- Physicians Clinic of Iowa
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Kentucky
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Elizabethtown, Kentucky, Forente stater, 42701
- Center For Arthritis and Osteoporosis
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Lexington, Kentucky, Forente stater, 40504
- Bluegrass Community Research, Inc.
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Maryland
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Cumberland, Maryland, Forente stater, 21502
- Klein And Associates, M.D., Pa
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Wheaton, Maryland, Forente stater, 20902
- The Center For Rheumatology And Bone Research
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Massachusetts
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Boston, Massachusetts, Forente stater, 02115
- Brigham and Women's Hospital
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Mansfield, Massachusetts, Forente stater, 02048
- Mansfield Health Center
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Michigan
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Battle Creek, Michigan, Forente stater, 49015
- Associated Internal Medicine Specialists
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Kalamazoo, Michigan, Forente stater, 49009
- Rheumatology Pc
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Mississippi
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Jackson, Mississippi, Forente stater, 39202
- Arthritis Associates Of Mississippi
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Missouri
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St.Louis, Missouri, Forente stater, 63131
- Physician Groups, Lc Dba
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Nevada
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Reno, Nevada, Forente stater, 89502
- Arthritis Center of Reno
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New Hampshire
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Dover, New Hampshire, Forente stater, 03820
- Seacoast Arthritis And Osteoporosis Center
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Nashua, New Hampshire, Forente stater, 03060
- Nashua Rheumatology
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New Mexico
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Las Cruces, New Mexico, Forente stater, 88011
- Arthritis and Osteoporosis Associates of New Mexico
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New York
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Lake Success, New York, Forente stater, 11042
- North Shore Lij Health System
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Mineola, New York, Forente stater, 11501
- Winthrop University Hospital
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Smithtown, New York, Forente stater, 11787
- Rheumatology Associates of Long Island
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North Carolina
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Asheville, North Carolina, Forente stater, 28803
- Asheville Rheumatology & Osteoporosis Research Asso P. A.
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Statesville, North Carolina, Forente stater, 28625
- Carolina Pharmaceutical Research
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Oklahoma
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Oklahoma City, Oklahoma, Forente stater, 73109
- Health Research Institute
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Oklahoma City, Oklahoma, Forente stater, 73103
- Health Research of Oklahoma
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Oklahoma City, Oklahoma, Forente stater, 73112
- Lynn Health Sciences Institute
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Pennsylvania
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Bethlehem, Pennsylvania, Forente stater, 18015
- East Penn Rheumatology Associates, P.C.
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Duncansville, Pennsylvania, Forente stater, 16635
- Altoona Center for Clinical Research
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Wyomissing, Pennsylvania, Forente stater, 19610
- Clinical Research Center of Reading, LLP
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South Carolina
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Charleston, South Carolina, Forente stater, 29406
- Low Country Rheumatology, PA
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Columbia, South Carolina, Forente stater, 29204
- Columbia Arthritis Center, P.A.
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Texas
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Austin, Texas, Forente stater, 78758
- Lovelace Scientific Resources, Inc.
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Dallas, Texas, Forente stater, 75246
- Arthritis Centers Of Texas
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Houston, Texas, Forente stater, 77004
- Rheumatic Disease Clinical Research Center, LLC
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Virginia
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Chesapeake, Virginia, Forente stater, 23320
- Center For Arthritis & Rheumatic Diseases, Pc
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Washington
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Spokane, Washington, Forente stater, 99202
- Rockwood Research Center
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West Virginia
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Clarksburg, West Virginia, Forente stater, 26301
- Mountain State Clinical Research
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Wisconsin
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Glendale, Wisconsin, Forente stater, 53217
- Rheumatic Disease Center
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Lima, Peru
- Local Institution
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Lima, Peru, LIMA 11
- Local Institution
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Lima, Peru, LIMA 33
- Local Institution
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Lima, Peru, LIMA 27
- Local Institution
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Callao 2
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Bellavista, Callao 2, Peru
- Local Institution
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Enkelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Aktiv komparator: Adalimumab
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Syringes, Subcutaneous, 40 mg, Biweekly Subcutaneous injections, 24 months (729 days)
Andre navn:
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Aktiv komparator: Abatacept
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Syringes, Subcutaneous, 125 mg/syringe for Subcutaneous, Weekly Subcutaneous injections, 24 months (729 days)
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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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
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Proportion of Participants With Local Injection Site Reactions Adverse Events (Pre-specified) Reported During 12 Month Period - ITT Population
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: Day 1 to Day 365
|
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.
|
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
Tidsramme: 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.
|
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
Tidsramme: 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.
|
Day 1 to Day 729
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- 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.
Hjelpsomme linker
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. oktober 2009
Primær fullføring (Faktiske)
1. oktober 2011
Studiet fullført (Faktiske)
1. november 2012
Datoer for studieregistrering
Først innsendt
29. juni 2009
Først innsendt som oppfylte QC-kriteriene
29. juni 2009
Først lagt ut (Anslag)
30. juni 2009
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
4. februar 2014
Siste oppdatering sendt inn som oppfylte QC-kriteriene
3. januar 2014
Sist bekreftet
1. januar 2014
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Sykdommer i immunsystemet
- Autoimmune sykdommer
- Leddsykdommer
- Muskel- og skjelettsykdommer
- Revmatiske sykdommer
- Bindevevssykdommer
- Leddgikt
- Leddgikt, revmatoid
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Anti-inflammatoriske midler
- Antirevmatiske midler
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Immune Checkpoint-hemmere
- Adalimumab
- Abatacept
Andre studie-ID-numre
- IM101-235
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .