Clinical trial NCT00122382: Remission and Joint Damage Progression in Early Rheumatoid Arthritis
Official title: A Phase IIIB Multi-center, Randomized, Double-Blind Study to Evaluate Remission and Joint Damage Progression in Methotrexate Naive Early Erosive RA Subjects Treated With Abatacept Plus Methotrexate Compared With Methotrexate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: abatacept, methotrexate, erosive RA
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2005-07-22
Enrollment: 1052
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a world wide study to evaluate the remission and joint damage in subjects treated with abatacept in addition to methotrexate versus subjects who receive methotrexate along with a placebo.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of rheumatoid arthritis (RA) \<=2 years; MTX naive or \<=10 mg/wk for \<=3 weeks. No dose within 3 months prior to informed consent.
* C-Reactive Protein (CRP) \>= 4.5 mg/L (after amendment)
* Rheumatoid factor or anti-cyclic citrullinated peptide antibody (anti-CCP) positive
* Tender joints \>=12 and swollen joints \>=10

Exclusion Criteria:

* Women and men who are not willing to use birth control
* Diagnosed with other rheumatic disease
* History of cancer within 5 years
* Active tuberculosis
* Treatment with another investigation drug within 28 days
* Active bacterial or viral infection

Primary outcomes:
measure: Number of Participants in DAS 28 C-reactive Protein (CRP) Remission at Month 12
timeFrame: Month 12
measure: Mean Change From Baseline in Radiographic Total Score to Month 12
timeFrame: Baseline, Month 12
measure: Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs During the Open-Label Period
timeFrame: Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
measure: Number of Participants With Serious Adverse Events Reported During the Open-Label Period
timeFrame: Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
measure: Number of Participants With SAEs With an Outcome of Death During the Open-label Period
timeFrame: Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
measure: Incidence Rates of Autoimmune Disorders in ABA-Treated Participants
timeFrame: Double Blind Period (+56 days post last dose in double-blind period or start of open-label period, whichever came first). Open-label period (56 days post last dose in the open-label period or start of maintenance sub-study, whichever came first).
measure: Incidence Rates of Infections and Infestations of Adverse Events in ABA-Treated Participants
timeFrame: Double Blind Period (+56 days post last dose in double-blind period or start of the open-label period, whichever came first). Open-label period (56 days post last dose in open-label period or start of maintenance sub-study, whichever came first).
measure: Incidence Rates of Malignant Neoplasm Adverse Events in ABA-Treated Participants
timeFrame: Double Blind Period (+56 days post last dose in double-blind period or start of the open-label period, whichever came first). Open-label period (56 days post last dose in open-label period or start of maintenance sub-study, whichever came first).
measure: Number of Participants With a Serious Acute-Infusional AE of Anaphylactic Shock During Open-Label Period
timeFrame: Open-Label Period (Month 12 to Month 24)
measure: Number of Participants With Select Blood Chemistry Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
timeFrame: Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
measure: Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
timeFrame: Continuously from start of open-label period up to 56 days post the last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
Secondary outcomes:
measure: Number of Participants With American College of Rheumatology (ACR) 50 Response at Month 12
timeFrame: Month 12
measure: Number of Participants With Major Clinical Response (MCR) at Month 12
timeFrame: Month 12
measure: Adjusted Mean Change From Baseline in DAS-28-CRP Score to Month 12
timeFrame: Baseline, Month 12
measure: Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 12
timeFrame: Month 12
measure: Adjusted Mean Change in Short Form 36 (SF-36) From Baseline to Month 12
timeFrame: Baseline, Month 12
measure: Mean Change From Baseline in Radiographic Erosion and Joint Space Narrowing (JSN) Scores to Month 12
timeFrame: Baseline, Month 12
measure: Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses in the Double-blind Period as Analyzed by Enzyme-linked-immunosorbent Serologic Assay (ELISA)
timeFrame: includes data up to approximately 85 days past the last dose of the double-blind period or start of the open-label period, whichever occurred first.
measure: Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses During the Open-Label Period (From Month 12 to Month 24) as Analyzed by ELISA
timeFrame: Includes open-label data up to approximately 85 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
measure: Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 24
timeFrame: Baseline, Month 24
measure: Mean Change From Baseline in Radiographic Total, Erosion and JSN Scores to Month 24
timeFrame: Baseline, Month 24
measure: Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) From Baseline at Month 24
timeFrame: Baseline, Month 24
measure: Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) at Month 24 in Participants Without Progression at Month 12
timeFrame: Month 12, Month 24
measure: Mean Difference Observed in Change From Baseline to Month 12 and Between Month 12 and Month 24 in Radiographic Scores (Total Score)
timeFrame: Baseline, Month 12, Month 24
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Reported During the Double-blind Period
timeFrame: Includes data up to 56 days post the last dose in the double-blind period or start of the open-label period, whichever occurred first.
measure: Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
timeFrame: Includes data up to 56 days post the last dose in the double-blind period or start of the open-label period, whichever occurred first.
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Rheumatology Associates Of North Alabama
state: Alabama
city: Huntington Beach
country: United States
facility: Talbert Medical Group
state: California
city: Colorado Springs
country: United States
facility: Arthritis Assoc And Osteo Ctr Of Col Sprgs
state: Colorado
city: Trumbull
country: United States
facility: New England Research Associates, Llc
state: Connecticut
city: Indianapolis
country: United States
facility: Diagnostic Rheumatology And Research
state: Indiana
city: Cumberland
country: United States
facility: Osteoporosis And Clinical Trials Center
state: Maryland
city: Hagerstown
country: United States
facility: Malamet & Klein, Md, Pa
state: Maryland
city: Lincoln
country: United States
facility: Arthritis Center Of Nebraska
state: Nebraska
city: Binghamton
country: United States
facility: Regional Rheumatology Associates
state: New York
city: Charlotte
country: United States
facility: Carolina Bone & Joint
state: North Carolina
city: Greenville
country: United States
facility: Physicians East, Pa
state: North Carolina
city: Statesville
country: United States
facility: Carolina Pharmaceutical Research
state: North Carolina
city: Norman
country: United States
facility: Lion Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Health Research Of Oklahoma
state: Oklahoma
city: Oklahoma City
country: United States
facility: Lynn Health Sciences Institute
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center For Clinical Research
state: Pennsylvania
city: Charleston
country: United States
facility: Low Country Research Center
state: South Carolina
city: Austin
country: United States
facility: Walter F Chase Md Pa
state: Texas
city: Arlington
country: United States
facility: Arthritis Clinic Of Northern Virginia, P.C.
state: Virginia
city: Malvern
country: Australia
facility: Local Institution
state: Victoria
city: Shenton Park
country: Australia
facility: Local Institution
state: Western Australia
city: Antwerpen
country: Belgium
facility: Local Institution
city: Bruxelles
country: Belgium
facility: Local Institution
city: Bruxelles
country: Belgium
facility: Local Institution
city: Hasselt
country: Belgium
facility: Local Institution
city: Leuven
country: Belgium
facility: Local Institution
city: Goiania
country: Brazil
facility: Local Institution
state: Goias
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: Rio De Janeiro - Rj
country: Brazil
facility: Local Institution
state: Rio De Janeiro
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: St. John'S
country: Canada
facility: Local Institution
state: Newfoundland and Labrador
city: Kitchener
country: Canada
facility: Local Institution
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Sherbrooke
country: Canada
facility: Local Institution
state: Quebec
city: Saskatoon
country: Canada
facility: Local Institution
state: Saskatchewan
city: Quebec
country: Canada
facility: Local Institution
city: Prague 2
country: Czech Republic
facility: Local Institution
city: Dijon
country: France
facility: Local Institution
city: Montpellier Cedex 5
country: France
facility: Local Institution
city: Nice Cedex 03
country: France
facility: Local Institution
city: Strasbourg Cedex
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Leipzig
country: Germany
facility: Local Institution
city: Leipzig
country: Germany
facility: Local Institution
city: Jesi(Ancona)
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Anyang
country: Korea, Republic of
facility: Local Institution
city: Daegu
country: Korea, Republic of
facility: Local Institution
city: Daejeon
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: D.f.
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Metepec
country: Mexico
facility: Local Institution
state: Estado De Mexico
city: Leon
country: Mexico
facility: Local Institution
state: Guanajuato
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Morelia
country: Mexico
facility: Local Institution
state: Michioacan
city: Cuernavaca
country: Mexico
facility: Local Institution
state: Morelos
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Chihuahua
country: Mexico
facility: Local Institution
city: San Luis Potosi
country: Mexico
facility: Local Institution
city: Amsterdam
country: Netherlands
facility: Local Institution
city: Leiden
country: Netherlands
facility: Local Institution
city: Nijmegen
country: Netherlands
facility: Local Institution
city: Poznan
country: Poland
facility: Local Institution
city: Poznan
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Ponce
country: Puerto Rico
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Bloemfontein
country: South Africa
facility: Local Institution
state: Free State
city: Muckleneuk
country: South Africa
facility: Local Institution
state: Gauteng
city: Pretoria
country: South Africa
facility: Local Institution
state: Gauteng
city: Berea
country: South Africa
facility: Local Institution
state: Kwa Zulu Natal
city: Panorama
country: South Africa
facility: Local Institution
state: Western Cape
city: A Coruna
country: Spain
facility: Local Institution
city: Santander
country: Spain
facility: Local Institution
city: Sevilla
country: Spain
facility: Local Institution
city: Manchester
country: United Kingdom
facility: Local Institution
state: Greater Manchester
city: Glasgow
country: United Kingdom
facility: Local Institution
state: Lanarkshire
city: Leeds
country: United Kingdom
facility: Local Institution
state: North Yorkshire
city: Newcastle
country: United Kingdom
facility: Local Institution
state: Northumberland
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Durez P, Westhovens R, Baeke F, Elbez Y, Robert S, Ahmad HA. Identification of poor prognostic joint locations in an early rheumatoid arthritis cohort at risk of rapidly progressing disease: a post-hoc analysis of the Phase III AGREE study. BMC Rheumatol. 2022 Apr 14;6(1):24. doi: 10.1186/s41927-022-00252-4.
citation: Jansen DTSL, Emery P, Smolen JS, Westhovens R, Le Bars M, Connolly SE, Ye J, Toes REM, Huizinga TWJ. Conversion to seronegative status after abatacept treatment in patients with early and poor prognostic rheumatoid arthritis is associated with better radiographic outcomes and sustained remission: post hoc analysis of the AGREE study. RMD Open. 2018 Mar 30;4(1):e000564. doi: 10.1136/rmdopen-2017-000564. eCollection 2018.
citation: Smolen JS, Wollenhaupt J, Gomez-Reino JJ, Grassi W, Gaillez C, Poncet C, Le Bars M, Westhovens R. Attainment and characteristics of clinical remission according to the new ACR-EULAR criteria in abatacept-treated patients with early rheumatoid arthritis: new analyses from the Abatacept study to Gauge Remission and joint damage progression in methotrexate (MTX)-naive patients with Early Erosive rheumatoid arthritis (AGREE). Arthritis Res Ther. 2015 Jun 11;17(1):157. doi: 10.1186/s13075-015-0671-9.
citation: Bathon J, Robles M, Ximenes AC, Nayiager S, Wollenhaupt J, Durez P, Gomez-Reino J, Grassi W, Haraoui B, Shergy W, Park SH, Genant H, Peterfy C, Becker JC, Covucci A, Moniz Reed D, Helfrick R, Westhovens R. Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes. Ann Rheum Dis. 2011 Nov;70(11):1949-56. doi: 10.1136/ard.2010.145268. Epub 2011 Aug 6.