Rheumatoid ArthritisPhase 3NCT00122382
Remission and Joint Damage Progression in Early Rheumatoid Arthritis
A Phase 3 study testing Abatacept and methotrexate in people with Rheumatoid Arthritis, run by Bristol-Myers Squibb at 89 sites in 18 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Abatacept and methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,052 participants
- Where
- 89 sitesin 18 countries
- Study dates
- Jul 2005to Feb 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
89 sites in 18 countries.
89 sites in 18 countries
United States19 sites
Arthritis Clinic Of Northern Virginia, P.C.
Arlington, Virginia, 22205
Walter F Chase Md Pa
Austin, Texas, 78705
Regional Rheumatology Associates
Binghamton, New York, 13905
Low Country Research Center
Charleston, South Carolina, 29406
Carolina Bone & Joint
Charlotte, North Carolina, 28210
Arthritis Assoc And Osteo Ctr Of Col Sprgs
Colorado Springs, Colorado, 80910
Osteoporosis And Clinical Trials Center
Cumberland, Maryland, 21502
Altoona Center For Clinical Research
Duncansville, Pennsylvania, 16635
Physicians East, Pa
Greenville, North Carolina, 27834
Malamet & Klein, Md, Pa
Hagerstown, Maryland, 21740
Talbert Medical Group
Huntington Beach, California, 92646
Rheumatology Associates Of North Alabama
Huntsville, Alabama, 35801
Diagnostic Rheumatology And Research
Indianapolis, Indiana, 46227
Arthritis Center Of Nebraska
Lincoln, Nebraska, 68516
Lion Research
Norman, Oklahoma, 73071
Health Research Of Oklahoma
Oklahoma City, Oklahoma, 73103
Lynn Health Sciences Institute
Oklahoma City, Oklahoma, 73112
Carolina Pharmaceutical Research
Statesville, North Carolina, 28625
New England Research Associates, Llc
Trumbull, Connecticut, 06611
Mexico11 sites
Local Institution
Chihuahua City, Chihuahua, 31000
Local Institution
Cuernavaca, Morelos, 62270
Local Institution
D.f., Mexico City, 06700
Local Institution
Guadalajara, Jalisco, 42650
Local Institution
Guadalajara, Jalisco, 44340
Local Institution
Guadalajara, Jalisco, 44690
Local Institution
León, Guanajuato, 37000
Local Institution
Metepec, State of Mexico, 52140
Local Institution
Monterrey, Nuevo León, 64020
Local Institution
Morelia, Michioacan, 58000
Local Institution
San Luis Potosí City, San Luis Potosí, 78240
Canada7 sites
Local Institution
Kitchener, Ontario, N2M 5N6
Local Institution
Montreal, Quebec, H2L 1S6
Local Institution
Québec, Quebec, G1V 3M7
Local Institution
Saskatoon, Saskatchewan, S7N 0W8
Local Institution
Sherbrooke, Quebec, J1H 5N4
Local Institution
St. John's, Newfoundland and Labrador, A1B 3E1
Local Institution
Toronto, Ontario, M5G 1X5
South Korea7 sites
Local Institution
Anyang, 431-070
Local Institution
Daegu, 705-718
Local Institution
Daejeon, 302-799
Local Institution
Seoul, 110-744
Local Institution
Seoul, 133-792
Local Institution
Seoul, 137-040
Local Institution
Seoul, 138-736
Brazil6 sites
Local Institution
Curitiba, Paraná, 80060
Local Institution
Goiânia, Goiás, 74043
Local Institution
Porto Alegre, Rio Grande do Sul, 91610
Local Institution
Rio de Janeiro - Rj, Rio de Janeiro, 20551
Local Institution
São Paulo, São Paulo, 04039
Local Institution
São Paulo, São Paulo, 04230
Belgium5 sites
Local Institution
Antwerp, 2020
Local Institution
Brussels, 1070
Local Institution
Brussels, 1200
Local Institution
Hasselt, 3500
Local Institution
Leuven, 3000
South Africa5 sites
Local Institution
Berea, KwaZulu-Natal, 4001
Local Institution
Bloemfontein, Free State, 9317
Local Institution
Muckleneuk, Gauteng, 0002
Local Institution
Panorama, Western Cape, 7506
Local Institution
Pretoria, Gauteng, 0084
France4 sites
Local Institution
Dijon, 21000
Local Institution
Montpellier, 34295
Local Institution
Nice, 06202
Local Institution
Strasbourg, 67098
Germany4 sites
Local Institution
Berlin, 14059
Local Institution
Hamburg, 22081
Local Institution
Leipzig, 04103
Local Institution
Leipzig, 04229
United Kingdom4 sites
Local Institution
Glasgow, Lanarkshire, G12 0YN
Local Institution
Leeds, North Yorkshire, LS7 4SA
Local Institution
Manchester, Greater Manchester, M13 9WL
Local Institution
Newcastle, Northumberland, NE1 4LP
Netherlands3 sites
Local Institution
Amsterdam, 1081 HV
Local Institution
Leiden, 2300 RC
Local Institution
Nijmegen, 6500 HB
Poland3 sites
Local Institution
Poznan, 60773
Local Institution
Poznan, 61-545
Local Institution
Warsaw, 02-637
Spain3 sites
Local Institution
A Coruña, 15706
Local Institution
Santander, 39008
Local Institution
Seville, 41071
Australia2 sites
Local Institution
Malvern, Victoria, 3144
Local Institution
Shenton Park, Western Australia, 6008
Italy2 sites
Local Institution
Jesi(Ancona), 60055
Local Institution
Milan, 20157
About this study
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
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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Abatacept, placebo, methotrexate
- Keywords
- abatacept, methotrexate, erosive RA
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbataceptDrug
abatacept 10 mg/kg IV monthly, methotrexate weekly, for 24 months
placeboDrug
placebo IV, monthly, methotrexate weekly for 12 months followed by abatacept 10 mg/kg IV monthly, methotrexate weekly for 12 months
methotrexateDrug
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
| Study group | Role | What they receive |
|---|---|---|
| ABA + MTX | Active comparator | abatacept 10 mg/kg intravenous (IV) + methotrexate Receives: Drug: Abatacept; Drug: methotrexate |
| Placebo (PLA) + MTX | Active comparator | placebo IV + methotrexate Receives: Drug: Abatacept; Drug: placebo; Drug: methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants in DAS 28 C-reactive Protein (CRP) Remission at Month 12
Number of participants who achieved remission at Month 12 of treatment, as defined by a Disease Activity Score (DAS) 28-CRP score of <2.6. DAS 28-CRP is a continuous measure, a composite of 4 variables: number of tender joints out of 28 joints, number of swollen joints out of 28 joints, CRP (in mg/L), and subject assessment of disease activity measure on a Visual Analogue Scale (VAS) of 100 millimeters (mm). The DAS28 scale=0 (best) to 10 (worst), indicating the current activity of the rheumatoid arthritis. A DAS28 >5.1 = high disease activity; <=3.2 = low disease activity; <2.6 = remission.
Measured: Month 12
Mean Change From Baseline in Radiographic Total Score to Month 12
To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and joint space narrowing (JSN). The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage.
Measured: Baseline, Month 12
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs During the Open-Label Period
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Related AE/SAE=Certain, Probable, Possible, or Missing. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Measured: 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.
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Measured: 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.
Number of Participants With SAEs With an Outcome of Death During the Open-label Period
Any untoward medical occurrence (SAE) that resulted in death
Measured: 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.
Incidence Rates of Autoimmune Disorders in ABA-Treated Participants
The incidence rates of autoimmune disorders are defined as the (number of patients experiencing the event/exposure within the period)*100 and are expressed in 100 person-years. Subjects experiencing the event had their exposure censored at the time of the 1st event.
Measured: 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).
Incidence Rates of Infections and Infestations of Adverse Events in ABA-Treated Participants
The incidence rates of infections and infestations are defined as the (number of patients experiencing the event /exposure within the period)*100 and are expressed in 100 person-years. Subjects experiencing the event had their exposure censored at the time of the 1st event.
Measured: 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).
Incidence Rates of Malignant Neoplasm Adverse Events in ABA-Treated Participants
The incidence rates of malignant neoplasms are defined as the (number of patients experiencing the event /exposure within the period)*100 and are expressed in 100 person-years. Subjects experiencing the event had their exposure censored at the time of the 1st event.
Measured: 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).
Number of Participants With a Serious Acute-Infusional AE of Anaphylactic Shock During Open-Label Period
There were 107 Prespecified, acute-infusional SAEs (occurring within 1 hour after the start of study drug infusion) pre-specified in the protocol; anaphylactic shock was the only one occuring in this study.
Measured: Open-Label Period (Month 12 to Month 24)
Number of Participants With Select Blood Chemistry Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Number of subjects with high liver function and kinedy tests: alkaline phosphatase (ALP) >2x upper limit of normal (ULN) or if pretreatment (PRE-RX) >ULN then >3x PRE-RX; aspartate aminotransferase (AST) >3x ULN or if PRE-RX >ULN then >4x PRE-RX; alanine aminotransferase (ALT) >3x ULN or if PRE-RX >ULN then >4x PRE-RX; g-glutamyl transferase (GGT)>2x ULN or if PRE-RX >ULN then >3x PRE-RX; total bilirubin >2x ULN or if PRE-RX >ULN then >4x PRE-RX; blood urea nitrogen >2x PRE-RX; creatinine >1.5x PRE-RX.
Measured: 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.
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Marked abnormalities in hemoglobin >3 g/dL decrease from PRE-RX; hematocrit <0.75x PRE-RX; erythrocytes <0.75x PRE-RX; platelet count <0.67x lower limit of normal (LLN) or >1.5x ULN or if PRE-RX <LLN then <0.5x PRE-RX and <100,000/mm3; leukocytes <0.75x LLN or >1.25x ULN or if PRE-RX <LLN then <0.8x PRE-RX or >ULN if PRE-RX >ULN then >1.2x PRE-RX or <LLN; neutrophils if value <1.00 x10^3 c/uL; lymphocytes if value <.750 x10^3 c/uL or if value >7.50 x10^3 c/uL; monocytes if value >2000/MM3; basophils if value >400/mm3; eosinophils if value >.750 x10^3 c/uL
Measured: 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 (15)
Number of Participants With American College of Rheumatology (ACR) 50 Response at Month 12
ACR 50 response was defined as a 50% improvement from baseline to Month 12 in tender and swollen joint counts and 50% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function), and 1 acute phase reactant value [ie, CRP].
Measured: Month 12
Number of Participants With Major Clinical Response (MCR) at Month 12
MCR was defined as 6 months of consecutive ACR 70 response at Month 12. ACR 70, the American College of Rheumatology (ACR) definition of 70% improvement was based on a 70% improvement (compared to baseline values) in tender and swollen joint counts and 70% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function, and 1 acute phase reactant value [ie, CRP]).
Measured: Month 12
Adjusted Mean Change From Baseline in DAS-28-CRP Score to Month 12
DAS 28-CRP is a continuous variable that is a composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, CRP in milligrams/Liter (mg/L), and subject assessment of disease activity measure on a Visual Analogue Scale (VAS) of 100 millimeters (mm). The DAS28 scale=0 to 10, indicating the current activity of the rheumatoid arthritis. A DAS28 >5.1=high disease activity; <3.2=low disease activity; <2.6=remission. Change from Baseline=Post-baseline - Baseline value; Adjusted for baseline value.
Measured: Baseline, Month 12
Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 12
Physical function was evaluated using the HAQ-disability index (HAQ-DI), a questionnaire with 20 questions assessing function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The questions are evaluated on a 4-point scale: 0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; 3 = unable to do. The 8 category scores are averaged into an overall HAQ-DI score on a scale from 0 (no disability) to 3 (completely disabled). Higher scores indicate greater dysfunction. HAQ response=improvement of at least 0.3 units from baseline.
Measured: Month 12
Adjusted Mean Change in Short Form 36 (SF-36) From Baseline to Month 12
The SF-36 covers 8 health dimensions: 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from 0 to 100, with a higher score indicating better quality of life. Two summary scores (physical and mental component summaries) were produced taking a weighted linear combination of the 8 individual subscales. Change from Baseline=Post-baseline - Baseline value; adjusted for baseline value.
Measured: Baseline, Month 12
Mean Change From Baseline in Radiographic Erosion and Joint Space Narrowing (JSN) Scores to Month 12
To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The erosion score range is 0 (no radiographic damage) to 145 (worst possible radiographic damage). The joint space narrowing score range is 0 (no radiographic damage) to 145 (worst possible radiographic damage). Higher scores indicated more damage. Change from baseline = Post-baseline - Baseline value
Measured: Baseline, Month 12
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)
Serum samples were analyzed by ELISA to detect antibodies against the whole molecule (both CTLA4 and Ig [anti-abatacept antibody]) or solely to CTLA4 (anti-CTLA4-T antibody). Reported as titer, the reciprocal of the sample dilution which yielded a signal equivalent to the statistically set cut point for the assay. For the anti-abatacept assay, minimum required dilution is 400-fold, therefore seronegative samples are those < lowest reportable titer (<400). For the anti-CTLA4-T assay, minimum required dilution is 25-fold, therefore seronegative samples are those < lowest reportable titer (<25).
Measured: 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.
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
Serum samples were analyzed by ELISA to detect antibodies against the whole molecule (both CTLA4 and Ig [anti-abatacept antibody]) or solely to CTLA4 (anti-CTLA4-T antibody). Reported as titer, the reciprocal of the sample dilution which yielded a signal equivalent to the statistically set cut point for the assay. For the anti-abatacept assay, minimum required dilution is 400-fold, therefore seronegative samples are those < lowest reportable titer (<400). For the anti-CTLA4-T assay, minimum required dilution is 25-fold, therefore seronegative samples are those < lowest reportable titer (<25).
Measured: 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.
Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 24
Physical function was evaluated using the HAQ-disability index (HAQ-DI), a questionnaire with 20 questions assessing function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The questions are evaluated on a 4-point scale: 0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; 3 = unable to do. The 8 category scores are averaged into an overall HAQ-DI score on a scale from 0 (no disability) to 3 (completely disabled). Higher scores indicate greater dysfunction. HAQ response=improvement of at least 0.3 units from baseline.
Measured: Baseline, Month 24
Mean Change From Baseline in Radiographic Total, Erosion and JSN Scores to Month 24
To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage. Change from baseline = Postbaseline - baseline value.
Measured: Baseline, Month 24
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) From Baseline at Month 24
Participants with no radiographic progression (defined as change in score <=0 or <=0.5), from baseline to Month 24. To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage.
Measured: Baseline, Month 24
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
Participants with no radiographic progression ((defined as change in score <=0 or <=0.5), sustained from Month 12 and Month 24. To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage.
Measured: Month 12, Month 24
Mean Difference Observed in Change From Baseline to Month 12 and Between Month 12 and Month 24 in Radiographic Scores (Total Score)
Mean difference observed in change from baseline to Month 12 and between Month 12 and Month 24 in radiographic scores (Total Score). To assess joint damage, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage.
Measured: Baseline, Month 12, Month 24
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Reported During the Double-blind Period
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Related AE/SAE=Certain, Probable, Possible, or Missing. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Measured: 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.
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Number of participants with laboratory values (hematology, liver and kidney functions, electrolytes, glucose tests, protein tests, metabolite tests, and urine chemistry tests) considered markedly abnormal according to prespecified protocol criteria
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2005 (estimated)
- Study startJul 2005
- Primary completionFeb 2008
- Study completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1,052 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00122382
- Sponsor's protocol ID
- IM101-023
- Status last verified
- Nov 2010
- First submitted
- 19 Jul 2005
- Last updated
- 16 Nov 2010
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 35418172Jansen 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.
PubMed 29657830Smolen 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.
PubMed 26063454Bathon 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.
PubMed 21821865
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00122382
- Acronym / sponsor ID
- IM101-023
- Conditions
- Rheumatoid Arthritis
- Keywords
- abatacept, methotrexate, erosive RA
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,052 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Jul 2005
- Primary completion
- Feb 2008 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 22 Jul 2005 (estimated)
- Results
- Posted 13 Jul 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ABA + MTX | Active comparator | Drug: Abatacept, Drug: methotrexateabatacept 10 mg/kg intravenous (IV) + methotrexate |
| Placebo (PLA) + MTX | Active comparator | Drug: Abatacept, Drug: placebo, Drug: methotrexateplacebo IV + methotrexate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Abataceptabatacept 10 mg/kg IV monthly, methotrexate weekly, for 24 months | Drug | ABA + MTX, Placebo (PLA) + MTX |
| placeboplacebo IV, monthly, methotrexate weekly for 12 months followed by abatacept 10 mg/kg IV monthly, methotrexate weekly for 12 months | Drug | Placebo (PLA) + MTX |
| methotrexateOral, 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 | Drug | ABA + MTX, Placebo (PLA) + MTX |
Primary outcome
Number of Participants in DAS 28 C-reactive Protein (CRP) Remission at Month 12
Time frame: Month 12
Number of participants who achieved remission at Month 12 of treatment, as defined by a Disease Activity Score (DAS) 28-CRP score of <2.6. DAS 28-CRP is a continuous measure, a composite of 4 variables: number of tender joints out of 28 joints, number of swollen joints out of 28 joints, CRP (in mg/L), and subject assessment of disease activity measure on a Visual Analogue Scale (VAS) of 100 millimeters (mm). The DAS28 scale=0 (best) to 10 (worst), indicating the current activity of the rheumatoid arthritis. A DAS28 >5.1 = high disease activity; <=3.2 = low disease activity; <2.6 = remission.
Mean Change From Baseline in Radiographic Total Score to Month 12
Time frame: Baseline, Month 12
To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and joint space narrowing (JSN). The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage.
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs During the Open-Label Period
Time frame: 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.
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Related AE/SAE=Certain, Probable, Possible, or Missing. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Time frame: 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.
SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Number of Participants With SAEs With an Outcome of Death During the Open-label Period
Time frame: 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.
Any untoward medical occurrence (SAE) that resulted in death
Incidence Rates of Autoimmune Disorders in ABA-Treated Participants
Time frame: 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).
The incidence rates of autoimmune disorders are defined as the (number of patients experiencing the event/exposure within the period)*100 and are expressed in 100 person-years. Subjects experiencing the event had their exposure censored at the time of the 1st event.
Incidence Rates of Infections and Infestations of Adverse Events in ABA-Treated Participants
Time frame: 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).
The incidence rates of infections and infestations are defined as the (number of patients experiencing the event /exposure within the period)*100 and are expressed in 100 person-years. Subjects experiencing the event had their exposure censored at the time of the 1st event.
Incidence Rates of Malignant Neoplasm Adverse Events in ABA-Treated Participants
Time frame: 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).
The incidence rates of malignant neoplasms are defined as the (number of patients experiencing the event /exposure within the period)*100 and are expressed in 100 person-years. Subjects experiencing the event had their exposure censored at the time of the 1st event.
Number of Participants With a Serious Acute-Infusional AE of Anaphylactic Shock During Open-Label Period
Time frame: Open-Label Period (Month 12 to Month 24)
There were 107 Prespecified, acute-infusional SAEs (occurring within 1 hour after the start of study drug infusion) pre-specified in the protocol; anaphylactic shock was the only one occuring in this study.
Number of Participants With Select Blood Chemistry Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Time frame: 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.
Number of subjects with high liver function and kinedy tests: alkaline phosphatase (ALP) >2x upper limit of normal (ULN) or if pretreatment (PRE-RX) >ULN then >3x PRE-RX; aspartate aminotransferase (AST) >3x ULN or if PRE-RX >ULN then >4x PRE-RX; alanine aminotransferase (ALT) >3x ULN or if PRE-RX >ULN then >4x PRE-RX; g-glutamyl transferase (GGT)>2x ULN or if PRE-RX >ULN then >3x PRE-RX; total bilirubin >2x ULN or if PRE-RX >ULN then >4x PRE-RX; blood urea nitrogen >2x PRE-RX; creatinine >1.5x PRE-RX.
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Time frame: 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.
Marked abnormalities in hemoglobin >3 g/dL decrease from PRE-RX; hematocrit <0.75x PRE-RX; erythrocytes <0.75x PRE-RX; platelet count <0.67x lower limit of normal (LLN) or >1.5x ULN or if PRE-RX <LLN then <0.5x PRE-RX and <100,000/mm3; leukocytes <0.75x LLN or >1.25x ULN or if PRE-RX <LLN then <0.8x PRE-RX or >ULN if PRE-RX >ULN then >1.2x PRE-RX or <LLN; neutrophils if value <1.00 x10^3 c/uL; lymphocytes if value <.750 x10^3 c/uL or if value >7.50 x10^3 c/uL; monocytes if value >2000/MM3; basophils if value >400/mm3; eosinophils if value >.750 x10^3 c/uL
15 secondary outcomes
Number of Participants With American College of Rheumatology (ACR) 50 Response at Month 12
Time frame: Month 12
Number of Participants With Major Clinical Response (MCR) at Month 12
Time frame: Month 12
Adjusted Mean Change From Baseline in DAS-28-CRP Score to Month 12
Time frame: Baseline, Month 12
Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 12
Time frame: Month 12
Adjusted Mean Change in Short Form 36 (SF-36) From Baseline to Month 12
Time frame: Baseline, Month 12
Mean Change From Baseline in Radiographic Erosion and Joint Space Narrowing (JSN) Scores to Month 12
Time frame: Baseline, Month 12
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)
Time frame: 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.
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
Time frame: 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.
Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 24
Time frame: Baseline, Month 24
Mean Change From Baseline in Radiographic Total, Erosion and JSN Scores to Month 24
Time frame: Baseline, Month 24
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) From Baseline at Month 24
Time frame: Baseline, Month 24
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
Time frame: Month 12, Month 24
Mean Difference Observed in Change From Baseline to Month 12 and Between Month 12 and Month 24 in Radiographic Scores (Total Score)
Time frame: Baseline, Month 12, Month 24
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Reported During the Double-blind Period
Time frame: 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.
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2010.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35418172Durez 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.
- Derived from this study: PubMed 29657830Jansen 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.
- Derived from this study: PubMed 26063454Smolen 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.
- Derived from this study: PubMed 21821865Bathon 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
89 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Abatacept and methotrexate in people with Rheumatoid Arthritis, run by Bristol-Myers Squibb at 89 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Nov 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 89 sites in United States, Mexico, Canada, South Korea, Brazil and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jul 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants in DAS 28 C-reactive Protein (CRP) Remission at Month 12 (time frame: Month 12). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00122382, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2010.