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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00122382




Registration number
NCT00122382
Ethics application status
Date submitted
19/07/2005
Date registered
22/07/2005
Date last updated
16/11/2010

Titles & IDs
Public title
Remission and Joint Damage Progression in Early Rheumatoid Arthritis
Scientific 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
Secondary ID [1] 0 0
IM101-023
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Abatacept
Treatment: Drugs - placebo
Treatment: Drugs - methotrexate

Active comparator: ABA + MTX - abatacept 10 mg/kg intravenous (IV) + methotrexate

Active comparator: Placebo (PLA) + MTX - placebo IV + methotrexate


Treatment: Drugs: Abatacept
abatacept 10 mg/kg IV monthly, methotrexate weekly, for 24 months

Treatment: Drugs: placebo
placebo IV, monthly, methotrexate weekly for 12 months followed by abatacept 10 mg/kg IV monthly, methotrexate weekly for 12 months

Treatment: Drugs: methotrexate
Oral, titrated to at least 15 mg per week not to exceed 20 mg per week administered every 28 days from Month 12 to Month 24
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants in DAS 28 C-reactive Protein (CRP) Remission at Month 12
Timepoint [1] 0 0
Month 12
Primary outcome [2] 0 0
Mean Change From Baseline in Radiographic Total Score to Month 12
Timepoint [2] 0 0
Baseline, Month 12
Primary outcome [3] 0 0
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs During the Open-Label Period
Timepoint [3] 0 0
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.
Primary outcome [4] 0 0
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Timepoint [4] 0 0
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.
Primary outcome [5] 0 0
Number of Participants With SAEs With an Outcome of Death During the Open-label Period
Timepoint [5] 0 0
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.
Primary outcome [6] 0 0
Incidence Rates of Autoimmune Disorders in ABA-Treated Participants
Timepoint [6] 0 0
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).
Primary outcome [7] 0 0
Incidence Rates of Infections and Infestations of Adverse Events in ABA-Treated Participants
Timepoint [7] 0 0
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).
Primary outcome [8] 0 0
Incidence Rates of Malignant Neoplasm Adverse Events in ABA-Treated Participants
Timepoint [8] 0 0
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).
Primary outcome [9] 0 0
Number of Participants With a Serious Acute-Infusional AE of Anaphylactic Shock During Open-Label Period
Timepoint [9] 0 0
Open-Label Period (Month 12 to Month 24)
Primary outcome [10] 0 0
Number of Participants With Select Blood Chemistry Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Timepoint [10] 0 0
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.
Primary outcome [11] 0 0
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Timepoint [11] 0 0
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 outcome [1] 0 0
Number of Participants With American College of Rheumatology (ACR) 50 Response at Month 12
Timepoint [1] 0 0
Month 12
Secondary outcome [2] 0 0
Number of Participants With Major Clinical Response (MCR) at Month 12
Timepoint [2] 0 0
Month 12
Secondary outcome [3] 0 0
Adjusted Mean Change From Baseline in DAS-28-CRP Score to Month 12
Timepoint [3] 0 0
Baseline, Month 12
Secondary outcome [4] 0 0
Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 12
Timepoint [4] 0 0
Month 12
Secondary outcome [5] 0 0
Adjusted Mean Change in Short Form 36 (SF-36) From Baseline to Month 12
Timepoint [5] 0 0
Baseline, Month 12
Secondary outcome [6] 0 0
Mean Change From Baseline in Radiographic Erosion and Joint Space Narrowing (JSN) Scores to Month 12
Timepoint [6] 0 0
Baseline, Month 12
Secondary outcome [7] 0 0
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)
Timepoint [7] 0 0
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.
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
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.
Secondary outcome [9] 0 0
Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 24
Timepoint [9] 0 0
Baseline, Month 24
Secondary outcome [10] 0 0
Mean Change From Baseline in Radiographic Total, Erosion and JSN Scores to Month 24
Timepoint [10] 0 0
Baseline, Month 24
Secondary outcome [11] 0 0
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) From Baseline at Month 24
Timepoint [11] 0 0
Baseline, Month 24
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
Month 12, Month 24
Secondary outcome [13] 0 0
Mean Difference Observed in Change From Baseline to Month 12 and Between Month 12 and Month 24 in Radiographic Scores (Total Score)
Timepoint [13] 0 0
Baseline, Month 12, Month 24
Secondary outcome [14] 0 0
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Reported During the Double-blind Period
Timepoint [14] 0 0
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.
Secondary outcome [15] 0 0
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Timepoint [15] 0 0
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.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2009
Sample size
Target
Accrual to date
Final
1052
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Local Institution - Malvern
Recruitment hospital [2] 0 0
Local Institution - Shenton Park
Recruitment postcode(s) [1] 0 0
3144 - Malvern
Recruitment postcode(s) [2] 0 0
6008 - Shenton Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Nebraska
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Oklahoma
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
South Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
Belgium
State/province [15] 0 0
Antwerpen
Country [16] 0 0
Belgium
State/province [16] 0 0
Bruxelles
Country [17] 0 0
Belgium
State/province [17] 0 0
Hasselt
Country [18] 0 0
Belgium
State/province [18] 0 0
Leuven
Country [19] 0 0
Brazil
State/province [19] 0 0
Goias
Country [20] 0 0
Brazil
State/province [20] 0 0
Parana
Country [21] 0 0
Brazil
State/province [21] 0 0
Rio De Janeiro
Country [22] 0 0
Brazil
State/province [22] 0 0
Rio Grande Do Sul
Country [23] 0 0
Brazil
State/province [23] 0 0
Sao Paulo
Country [24] 0 0
Canada
State/province [24] 0 0
Newfoundland and Labrador
Country [25] 0 0
Canada
State/province [25] 0 0
Ontario
Country [26] 0 0
Canada
State/province [26] 0 0
Quebec
Country [27] 0 0
Canada
State/province [27] 0 0
Saskatchewan
Country [28] 0 0
Czech Republic
State/province [28] 0 0
Prague 2
Country [29] 0 0
France
State/province [29] 0 0
Dijon
Country [30] 0 0
France
State/province [30] 0 0
Montpellier Cedex 5
Country [31] 0 0
France
State/province [31] 0 0
Nice Cedex 03
Country [32] 0 0
France
State/province [32] 0 0
Strasbourg Cedex
Country [33] 0 0
Germany
State/province [33] 0 0
Berlin
Country [34] 0 0
Germany
State/province [34] 0 0
Hamburg
Country [35] 0 0
Germany
State/province [35] 0 0
Leipzig
Country [36] 0 0
Italy
State/province [36] 0 0
Jesi(Ancona)
Country [37] 0 0
Italy
State/province [37] 0 0
Milano
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Anyang
Country [39] 0 0
Korea, Republic of
State/province [39] 0 0
Daegu
Country [40] 0 0
Korea, Republic of
State/province [40] 0 0
Daejeon
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Seoul
Country [42] 0 0
Mexico
State/province [42] 0 0
Distrito Federal
Country [43] 0 0
Mexico
State/province [43] 0 0
Estado De Mexico
Country [44] 0 0
Mexico
State/province [44] 0 0
Guanajuato
Country [45] 0 0
Mexico
State/province [45] 0 0
Jalisco
Country [46] 0 0
Mexico
State/province [46] 0 0
Michioacan
Country [47] 0 0
Mexico
State/province [47] 0 0
Morelos
Country [48] 0 0
Mexico
State/province [48] 0 0
Nuevo Leon
Country [49] 0 0
Mexico
State/province [49] 0 0
Chihuahua
Country [50] 0 0
Mexico
State/province [50] 0 0
San Luis Potosi
Country [51] 0 0
Netherlands
State/province [51] 0 0
Amsterdam
Country [52] 0 0
Netherlands
State/province [52] 0 0
Leiden
Country [53] 0 0
Netherlands
State/province [53] 0 0
Nijmegen
Country [54] 0 0
Poland
State/province [54] 0 0
Poznan
Country [55] 0 0
Poland
State/province [55] 0 0
Warszawa
Country [56] 0 0
Puerto Rico
State/province [56] 0 0
Ponce
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Moscow
Country [58] 0 0
South Africa
State/province [58] 0 0
Free State
Country [59] 0 0
South Africa
State/province [59] 0 0
Gauteng
Country [60] 0 0
South Africa
State/province [60] 0 0
Kwa Zulu Natal
Country [61] 0 0
South Africa
State/province [61] 0 0
Western Cape
Country [62] 0 0
Spain
State/province [62] 0 0
A Coruna
Country [63] 0 0
Spain
State/province [63] 0 0
Santander
Country [64] 0 0
Spain
State/province [64] 0 0
Sevilla
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Greater Manchester
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Lanarkshire
Country [67] 0 0
United Kingdom
State/province [67] 0 0
North Yorkshire
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Northumberland

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00122382
Trial related presentations / publications
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00122382