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

NCT ID: NCT01142726

Last Updated: 2016-01-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

511 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-12-31

Study Completion Date

2014-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Abatacept, 125 mg, plus methotrexate, 2.5 mg

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

Group Type ACTIVE_COMPARATOR

Abatacept

Intervention Type DRUG

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

Methotrexate

Intervention Type DRUG

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

Methotrexate, 2.5 mg, plus abatacept placebo

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

Group Type ACTIVE_COMPARATOR

Methotrexate

Intervention Type DRUG

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

Abatacept placebo

Intervention Type DRUG

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

Abatacept, 125 mg, plus methotrexate placebo

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

Group Type ACTIVE_COMPARATOR

Abatacept

Intervention Type DRUG

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

Methotrexate placebo

Intervention Type DRUG

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

Interventions

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Abatacept

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

Intervention Type DRUG

Methotrexate

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

Intervention Type DRUG

Abatacept placebo

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

Intervention Type DRUG

Methotrexate placebo

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

Intervention Type DRUG

Other Intervention Names

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Orencia BMS 188667 Rheumatrex

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Rheumatology Associates Of North Alabama, P.C.

Huntsville, Alabama, United States

Site Status

St. Joseph'S Mercy Clinic

Hot Springs, Arkansas, United States

Site Status

Sarasota Arthritis Research Center

Sarasota, Florida, United States

Site Status

Coeur D'Alene Arthrit Clin

Coeur d'Alene, Idaho, United States

Site Status

Johns Hopkins University Division Of Rheumatology

Baltimore, Maryland, United States

Site Status

Clinical Pharmacology Study Group

Worcester, Massachusetts, United States

Site Status

Arthritis Associates Of Mississippi

Jackson, Mississippi, United States

Site Status

Physician Research Collaboration, Llc

Lincoln, Nebraska, United States

Site Status

Piedmont Rheumatology, Pa

Hickory, North Carolina, United States

Site Status

Carolina Arthritis Associates

Wilmington, North Carolina, United States

Site Status

Metrohealth Medical Center

Cleveland, Ohio, United States

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Isam A. Diab, Md

Middleburg, Ohio, United States

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Alan J. Kivitz, Md, Cpi

Duncansville, Pennsylvania, United States

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Mitchell C. Feinman, Md

Orangeburg, South Carolina, United States

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Kurt Oelke, Md

Glendale, Wisconsin, United States

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Local Institution

Cairns, Queensland, Australia

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Maroochydore, Queensland, Australia

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Woodville, South Australia, Australia

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Heidelberg, Victoria, Australia

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Malvern, Victoria, Australia

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Victoria Park, Western Australia, Australia

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Brussels, , Belgium

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Kortrijk, , Belgium

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Merksem, , Belgium

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Calgary, Alberta, Canada

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Laval, Quebec, Canada

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Hjørring, , Denmark

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Helsinki, , Finland

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Tampere, , Finland

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Chambray-lès-Tours, , France

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Montpellier, , France

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Paris, , France

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Poitiers, , France

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Berlin, , Germany

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Berlin, , Germany

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Hildesheim, , Germany

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München, , Germany

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München, , Germany

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München, , Germany

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Ancona, , Italy

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Siena, , Italy

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Chihuahua City, Chihuahua, Mexico

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Guadalajara, Jalisco, Mexico

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Guadalajara, Jalisco, Mexico

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Monterrey, Nuevo León, Mexico

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San Luis Potosí City, San Luis Potosí, Mexico

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Metepec, State of Mexico, Mexico

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Mérida, Yucatán, Mexico

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Querétaro, , Mexico

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Lublin, , Poland

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Poznan, , Poland

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Torun, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Wroc#aw, , Poland

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Moscow, , Russia

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Moscow, , Russia

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Tver', , Russia

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Kempton Park, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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Durban, KwaZulu-Natal, South Africa

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Panorama, Western Cape, South Africa

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Daegu, , South Korea

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Daejeon, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Gothenburg, , Sweden

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Linköping, , Sweden

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Malmo, , Sweden

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Stockholm, , Sweden

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Uppsala, , Sweden

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Countries

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United States Australia Belgium Canada Denmark Finland France Germany Italy Mexico Poland Russia South Africa South Korea Sweden

References

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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.

Reference Type DERIVED
PMID: 35172859 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31819995 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31278695 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30997151 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30341453 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26865601 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25367713 (View on PubMed)

Related Links

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Other Identifiers

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2010-018674-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IM101-226

Identifier Type: -

Identifier Source: org_study_id

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