Remission and Joint Damage Progression in Early Rheumatoid Arthritis

NCT00122382 | Completed Phase 3 Results

• 1 other identifier: IM101-023
• Study Type: interventional
• Target: 1,052
• Locations: 18 countries
• Sites: 89

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.

Conditions

Rheumatoid Arthritis

Keywords

abatacept, methotrexate, erosive RA

Outcome Measures

Primary Outcomes (11)

• 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.

  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.

  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.

  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.

  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

  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.

  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.

  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.

  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.

  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.

  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

  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

  Month 12

• Number of Participants With Major Clinical Response (MCR) at Month 12

  Month 12

• Adjusted Mean Change From Baseline in DAS-28-CRP Score to Month 12

  Baseline, Month 12

• Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 12

  Month 12

• Adjusted Mean Change in Short Form 36 (SF-36) From Baseline to Month 12

  Baseline, Month 12

Study Arms (2)

ABA + MTX

ACTIVE COMPARATOR

abatacept 10 mg/kg intravenous (IV) + methotrexate

Drug: Abatacept; Drug: methotrexate

Placebo (PLA) + MTX

ACTIVE COMPARATOR

placebo IV + methotrexate

Drug: Abatacept; Drug: placebo; Drug: methotrexate

Interventions

Abatacept DRUG

abatacept 10 mg/kg IV monthly, methotrexate weekly, for 24 months

ABA + MTX; Placebo (PLA) + MTX

placebo DRUG

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

Placebo (PLA) + MTX

methotrexate DRUG

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

ABA + MTX; Placebo (PLA) + MTX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (89)

Rheumatology Associates Of North Alabama

Huntsville, Alabama, 35801, United States

Location

Talbert Medical Group

Huntington Beach, California, 92646, United States

Location

Arthritis Assoc And Osteo Ctr Of Col Sprgs

Colorado Springs, Colorado, 80910, United States

Location

New England Research Associates, Llc

Trumbull, Connecticut, 06611, United States

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Diagnostic Rheumatology And Research

Indianapolis, Indiana, 46227, United States

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Osteoporosis And Clinical Trials Center

Cumberland, Maryland, 21502, United States

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Malamet & Klein, Md, Pa

Hagerstown, Maryland, 21740, United States

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Arthritis Center Of Nebraska

Lincoln, Nebraska, 68516, United States

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Regional Rheumatology Associates

Binghamton, New York, 13905, United States

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Carolina Bone & Joint

Charlotte, North Carolina, 28210, United States

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Physicians East, Pa

Greenville, North Carolina, 27834, United States

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Carolina Pharmaceutical Research

Statesville, North Carolina, 28625, United States

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Lion Research

Norman, Oklahoma, 73071, United States

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Health Research Of Oklahoma

Oklahoma City, Oklahoma, 73103, United States

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Lynn Health Sciences Institute

Oklahoma City, Oklahoma, 73112, United States

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Altoona Center For Clinical Research

Duncansville, Pennsylvania, 16635, United States

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Low Country Research Center

Charleston, South Carolina, 29406, United States

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Walter F Chase Md Pa

Austin, Texas, 78705, United States

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Arthritis Clinic Of Northern Virginia, P.C.

Arlington, Virginia, 22205, United States

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Local Institution

Malvern, Victoria, 3144, Australia

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Shenton Park, Western Australia, 6008, Australia

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Antwerp, 2020, Belgium

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Brussels, 1070, Belgium

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Brussels, 1200, Belgium

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Hasselt, 3500, Belgium

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Leuven, 3000, Belgium

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Goiânia, Goiás, 74043, Brazil

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Curitiba, Paraná, 80060, Brazil

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Rio de Janeiro - Rj, Rio de Janeiro, 20551, Brazil

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Porto Alegre, Rio Grande do Sul, 91610, Brazil

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São Paulo, São Paulo, 04039, Brazil

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São Paulo, São Paulo, 04230, Brazil

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St. John's, Newfoundland and Labrador, A1B 3E1, Canada

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Kitchener, Ontario, N2M 5N6, Canada

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Toronto, Ontario, M5G 1X5, Canada

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Montreal, Quebec, H2L 1S6, Canada

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Québec, Quebec, G1V 3M7, Canada

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Sherbrooke, Quebec, J1H 5N4, Canada

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Saskatoon, Saskatchewan, S7N 0W8, Canada

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Prague, 128 50, Czechia

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Dijon, 21000, France

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Montpellier, 34295, France

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Nice, 06202, France

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Strasbourg, 67098, France

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Berlin, 14059, Germany

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Hamburg, 22081, Germany

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Leipzig, 04103, Germany

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Leipzig, 04229, Germany

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Jesi(Ancona), 60055, Italy

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Milan, 20157, Italy

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Chihuahua City, Chihuahua, 31000, Mexico

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León, Guanajuato, 37000, Mexico

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Guadalajara, Jalisco, 42650, Mexico

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Guadalajara, Jalisco, 44340, Mexico

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Guadalajara, Jalisco, 44690, Mexico

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D.f., Mexico City, 06700, Mexico

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Morelia, Michioacan, 58000, Mexico

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Cuernavaca, Morelos, 62270, Mexico

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Monterrey, Nuevo León, 64020, Mexico

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San Luis Potosí City, San Luis Potosí, 78240, Mexico

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Metepec, State of Mexico, 52140, Mexico

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Amsterdam, 1081 HV, Netherlands

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Leiden, 2300 RC, Netherlands

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Nijmegen, 6500 HB, Netherlands

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Poznan, 60773, Poland

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Poznan, 61-545, Poland

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Warsaw, 02-637, Poland

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Ponce, 00716, Puerto Rico

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Moscow, 115522, Russia

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Moscow, 119049, Russia

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Bloemfontein, Free State, 9317, South Africa

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Muckleneuk, Gauteng, 0002, South Africa

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Pretoria, Gauteng, 0084, South Africa

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Berea, KwaZulu-Natal, 4001, South Africa

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Panorama, Western Cape, 7506, South Africa

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Anyang, 431-070, South Korea

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Daegu, 705-718, South Korea

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Daejeon, 302-799, South Korea

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Seoul, 110-744, South Korea

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Seoul, 133-792, South Korea

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Seoul, 137-040, South Korea

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Seoul, 138-736, South Korea

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A Coruña, 15706, Spain

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Santander, 39008, Spain

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Seville, 41071, Spain

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Manchester, Greater Manchester, M13 9WL, United Kingdom

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Glasgow, Lanarkshire, G12 0YN, United Kingdom

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Leeds, North Yorkshire, LS7 4SA, United Kingdom

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Newcastle, Northumberland, NE1 4LP, United Kingdom

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Related Publications (4)

• 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.

  PMID: 35418172 DERIVED

• 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.

  PMID: 29657830 DERIVED

• 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.

  PMID: 26063454 DERIVED

• 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.

  PMID: 21821865 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Abatacept; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 19, 2005
• First Posted: July 22, 2005
• Study Start: July 1, 2005
• Primary Completion: February 1, 2008
• Study Completion: February 1, 2009
• Last Updated: November 16, 2010
• Results First Posted: July 13, 2010

Record last verified: 2010-11

Locations

RU (2); FR (4); US (19); AU (2); CA (7); NL (3); ME (11); BE (5); BR (6); PR (1); CZ (1); ES (3); GB (4); IT (2); PL (3); KR (7); DE (4); ZA (5)