Efficacy and Safety Study of Abatacept Subcutaneous Plus Methotrexate in Inducing Remission in Adults With Very Early Rheumatoid Arthritis

NCT01142726 | Completed Phase 3 Results

• 2 other identifiers: IM101-2262010-018674-20
• Study Type: interventional
• Target: 511
• Locations: 15 countries
• Sites: 73

Brief Summary

The primary purpose of the protocol is to demonstrate the ability of abatacept plus methotrexate to induce remission in patients with very early rheumatoid arthritis after 12 months of treatment and to maintain remission following 6 months of drug withdrawal.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18

  DAS28-CRP remission defined as \<2.6; TP=treatment phase; WP=withdrawal phase. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). These measures are then fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)

  Randomization to Months 12 and 18

Secondary Outcomes (19)

• Percentage of Participants Who Received Monotherapy and Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18

  Randomization to Months 12 and 18

• Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population

  Randomization to Month 24

• Adjusted Mean Change From Baseline in Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) at Months 6, 12, and 18

  Baseline to Month 18

• Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) at Months 12 and 18

  Randomization to Month 18

• Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time

  Randomization to Month 18

Study Arms (3)

Abatacept, 125 mg, plus methotrexate, 2.5 mg

ACTIVE COMPARATOR

Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period

Drug: Abatacept; Drug: Methotrexate

Methotrexate, 2.5 mg, plus abatacept placebo

ACTIVE COMPARATOR

Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period

Drug: Methotrexate; Drug: Abatacept placebo

Abatacept, 125 mg, plus methotrexate placebo

ACTIVE COMPARATOR

Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period

Drug: Abatacept; Drug: Methotrexate placebo

Interventions

Abatacept DRUG

Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months

Also known as: Orencia, BMS 188667

Abatacept, 125 mg, plus methotrexate placebo; Abatacept, 125 mg, plus methotrexate, 2.5 mg

Methotrexate DRUG

Tablets, oral, 2.5 mg, once weekly, 12 months

Also known as: Rheumatrex

Abatacept, 125 mg, plus methotrexate, 2.5 mg; Methotrexate, 2.5 mg, plus abatacept placebo

Abatacept placebo DRUG

Injection, subcutaneous, to match 125 mg by syringe, once weekly, 12 months

Methotrexate, 2.5 mg, plus abatacept placebo

Methotrexate placebo DRUG

Tablets, oral, to match 2.5-mg tablet, once weekly, 12 months

Abatacept, 125 mg, plus methotrexate placebo

Eligibility Criteria

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

You may qualify if:

• Presence of active clinical synovitis in at least 2 joints, 1 of which must have been a small joint, for a minimum of 8 weeks prior to screening
• Onset of persistent symptoms ≤ 2 years prior to screening
• Positive test result for anticyclic citrullinated peptides 2
• Methotrexate naive or with minimum exposure to methotrexate, defined as no more than 10 mg/week for ≤4 weeks and no methotrexate dose for 1 month prior to screening visit
• Biologic naive, including no treatment with an investigational biologic prior to screening
• Disease Activity Score 28 based on C-reactive protein score ≥3.2 at screening
• Withdrawal from any treatment with chloroquine, hydroxychloroquine, and/or sulfasalazine (wash-out) for a minimum of 28 days prior to randomization
• If receiving oral corticosteroids, on a stable low dose (≤ 10 mg/day prednisone equivalent) for at least 4 weeks
• Able to undergo magnetic resonance imaging

You may not qualify if:

• Meeting diagnostic criteria for other rheumatic disease (eg, lupus erythematosus)
• Treatment with an intravenous, intramuscular, or intraarticular corticosteroid within 4 weeks prior to randomization
• Scheduled for or anticipating joint replacement surgery
• Presence of concomitant illness likely to require systemic glucocorticosteroid therapy during the study, in the opinion of the investigator
• History of malignancy in the last 5 years
• Any serious bacterial infection within the last 3 months not treated or resolved with antibiotics, or any chronic or recurrent bacterial infection
• At risk for tuberculosis
• Evidence of active or latent bacterial or viral infection at the time of potential enrollment, including human immunodeficiency or herpes zoster virus or cytomegalovirus that resolved less than 2 months prior to enrollment

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (73)

Rheumatology Associates Of North Alabama, P.C.

Huntsville, Alabama, 35801, United States

Location

St. Joseph'S Mercy Clinic

Hot Springs, Arkansas, 71913, United States

Location

Sarasota Arthritis Research Center

Sarasota, Florida, 34239, United States

Location

Coeur D'Alene Arthrit Clin

Coeur d'Alene, Idaho, 83814, United States

Location

Johns Hopkins University Division Of Rheumatology

Baltimore, Maryland, 21224, United States

Location

Clinical Pharmacology Study Group

Worcester, Massachusetts, 01605, United States

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Arthritis Associates Of Mississippi

Jackson, Mississippi, 39202, United States

Location

Physician Research Collaboration, Llc

Lincoln, Nebraska, 68516, United States

Location

Piedmont Rheumatology, Pa

Hickory, North Carolina, 28602, United States

Location

Carolina Arthritis Associates

Wilmington, North Carolina, 28401, United States

Location

Metrohealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Isam A. Diab, Md

Middleburg, Ohio, 44130, United States

Location

Alan J. Kivitz, Md, Cpi

Duncansville, Pennsylvania, 16635, United States

Location

Mitchell C. Feinman, Md

Orangeburg, South Carolina, 29118, United States

Location

Kurt Oelke, Md

Glendale, Wisconsin, 53217, United States

Location

Local Institution

Cairns, Queensland, 4870, Australia

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Maroochydore, Queensland, 4558, Australia

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Woodville, South Australia, 5011, Australia

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Heidelberg, Victoria, 3084, Australia

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Malvern, Victoria, 3144, Australia

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Victoria Park, Western Australia, 6100, Australia

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Brussels, 1200, Belgium

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Kortrijk, 8500, Belgium

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Merksem, 2170, Belgium

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Calgary, Alberta, T2N 4N1, Canada

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Laval, Quebec, H7T 2P5, Canada

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Hjørring, 9800, Denmark

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Helsinki, 00290, Finland

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Tampere, 33521, Finland

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Chambray-lès-Tours, 37170, France

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Montpellier, 34295, France

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Paris, 75679, France

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Poitiers, 86021, France

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Berlin, 10117, Germany

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Berlin, 14059, Germany

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Hildesheim, 31134, Germany

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München, 80336, Germany

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München, 80639, Germany

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München, 81541, Germany

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Ancona, 60055, Italy

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Siena, 53100, Italy

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Chihuahua City, Chihuahua, 31000, Mexico

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Guadalajara, Jalisco, 44500, Mexico

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Guadalajara, Jalisco, 44690, 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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Mérida, Yucatán, 97000, Mexico

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Querétaro, 76178, Mexico

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Lublin, 20-954, Poland

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Poznan, 60-218, Poland

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Torun, 87100, Poland

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Warsaw, 01-157, Poland

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Warsaw, 01-868, Poland

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Wroc#aw, 50-088, Poland

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Moscow, 117049, Russia

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Moscow, 129327, Russia

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Tver', 170036, Russia

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Kempton Park, Gauteng, 1619, South Africa

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Pretoria, Gauteng, 0083, South Africa

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Pretoria, Gauteng, 0084, South Africa

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Pretoria, Gauteng, 0181, South Africa

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Durban, KwaZulu-Natal, 4001, South Africa

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Panorama, Western Cape, 7500, South Africa

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Daegu, 705-718, South Korea

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Daejeon, 302-799, South Korea

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Seoul, 133-791, South Korea

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Seoul, 137-701, South Korea

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Gothenburg, 413 45, Sweden

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Linköping, 581 85, Sweden

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Malmo, 205 02, Sweden

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Stockholm, 171 76, Sweden

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Uppsala, 751 85, Sweden

Location

Related Publications (7)

• Ahmad HA, Baker JF, Conaghan PG, Emery P, Huizinga TWJ, Elbez Y, Banerjee S, Ostergaard M. Prediction of flare following remission and treatment withdrawal in early rheumatoid arthritis: post hoc analysis of a phase IIIb trial with abatacept. Arthritis Res Ther. 2022 Feb 16;24(1):47. doi: 10.1186/s13075-022-02735-8.

  PMID: 35172859 DERIVED

• Keystone EC, Ahmad HA, Yazici Y, Bergman MJ. Disease activity measures at baseline predict structural damage progression: data from the randomized, controlled AMPLE and AVERT trials. Rheumatology (Oxford). 2020 Aug 1;59(8):2090-2098. doi: 10.1093/rheumatology/kez455.

  PMID: 31819995 DERIVED

• Ahmad HA, Baker JF, Ostergaard M, Ye J, Emery P, Conaghan PG. Determining MRI Inflammation Targets When Considering a Rheumatoid Arthritis Treat-to-Target Strategy: Results of a Randomized, Placebo-Controlled Trial. Adv Ther. 2019 Sep;36(9):2384-2393. doi: 10.1007/s12325-019-01020-6. Epub 2019 Jul 5.

  PMID: 31278695 DERIVED

• Emery P, Burmester GR, Bykerk VP, Combe BG, Furst DE, Maldonado MA, Huizinga TW. Re-treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis: 2-year results from the AVERT study. RMD Open. 2019 Feb 8;5(1):e000840. doi: 10.1136/rmdopen-2018-000840. eCollection 2019.

  PMID: 30997151 DERIVED

• Bykerk VP, Burmester GR, Combe BG, Furst DE, Huizinga TWJ, Ahmad HA, Emery P. On-drug and drug-free remission by baseline symptom duration: abatacept with methotrexate in patients with early rheumatoid arthritis. Rheumatol Int. 2018 Dec;38(12):2225-2231. doi: 10.1007/s00296-018-4173-3. Epub 2018 Oct 20.

  PMID: 30341453 DERIVED

• Peterfy C, Burmester GR, Bykerk VP, Combe BG, DiCarlo JC, Furst DE, Huizinga TW, Wong DA, Conaghan PG, Emery P. Sustained improvements in MRI outcomes with abatacept following the withdrawal of all treatments in patients with early, progressive rheumatoid arthritis. Ann Rheum Dis. 2016 Aug;75(8):1501-5. doi: 10.1136/annrheumdis-2015-208258. Epub 2016 Feb 10.

  PMID: 26865601 DERIVED

• Emery P, Burmester GR, Bykerk VP, Combe BG, Furst DE, Barre E, Karyekar CS, Wong DA, Huizinga TW. Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann Rheum Dis. 2015 Jan;74(1):19-26. doi: 10.1136/annrheumdis-2014-206106. Epub 2014 Nov 3.

  PMID: 25367713 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

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: Bristol-Myers Squibb 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
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2010
• First Posted: June 11, 2010
• Study Start: December 1, 2010
• Primary Completion: September 1, 2013
• Study Completion: October 1, 2014
• Last Updated: January 14, 2016
• Results First Posted: October 17, 2014

Record last verified: 2015-12

Locations

DK (1); ME (8); FI (2); PL (6); ZA (6); SE (5); DE (6); BE (3); FR (4); CA (2); IT (2); AU (6); RU (3); US (15); KR (4)