Clinical trial NCT01142726: Efficacy and Safety Study of Abatacept Subcutaneous Plus Methotrexate in Inducing Remission in Adults With Very Early Rheumatoid Arthritis
Official title: A Phase 3b, Randomized, Active Controlled Trial to Evaluate the Efficacy and Safety of Abatacept SC in Combination With Methotrexate in Inducing Clinical Remission Compared to Methotrexate Monotherapy in Adults With Very Early RA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2010-06-11
Enrollment: 511
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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

Key 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

Primary outcomes:
measure: 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
timeFrame: Randomization to Months 12 and 18
Secondary outcomes:
measure: 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
timeFrame: Randomization to Months 12 and 18
measure: Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population
timeFrame: Randomization to Month 24
measure: Adjusted Mean Change From Baseline in Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) at Months 6, 12, and 18
timeFrame: Baseline to Month 18
measure: Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) at Months 12 and 18
timeFrame: Randomization to Month 18
measure: Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time
timeFrame: Randomization to Month 18
measure: Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time
timeFrame: Randomization to Month 24
measure: Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time
timeFrame: Randomization to Month 18
measure: Adjusted Mean Change From Baseline at Months 6, 12, and 18 in Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of Short Form-36 (SF-36)
timeFrame: Randomization to Months 6, 12, and 18
measure: Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI)
timeFrame: Randomization to Month 18
measure: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Related Adverse Events (AEs), and Discontinuations Due to AEs During the Treatment Period
timeFrame: Day 1 to up to 56 days following the last dosing day (Day 365); all deaths during study period, including those that occurred >56 days after last dose in Treatment Period
measure: Adverse Events (AEs) of Interest During the Treatment Period
timeFrame: Day 1 to 56 days following last dosing day (Day 365)
measure: Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period
timeFrame: Day 1 up to 56 days following the last dosing day in the Treatment Period (Day 365)
measure: Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time During Withdrawal Period- Treated Participants in Remission at Month 12
timeFrame: End of Treatment Period (Month 12) to End of Withdrawal Period (Month 24)
measure: Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period
timeFrame: Randomization to Month 24
measure: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) and Discontinuations Due to AEs During the Full Study (All Periods)
timeFrame: Day 1 to 56 days post last dose in the study, up to Month 30
measure: Adverse Events (AEs) of Interest During the Withdrawal Period
timeFrame: Last dose in TP + 57 days, up to Month 24
measure: Adverse Events (AEs) of Interest During the Re-exposure Period
timeFrame: First dose in Re-exposure period up to last dose of Re-exposure Period + 56 days
measure: Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period
timeFrame: Last dose in TP + 57 days, up to Month 24
measure: Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period
timeFrame: Start of re-exposure period to 56 days post last dose, up to Month 30
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Rheumatology Associates Of North Alabama, P.C.
state: Alabama
city: Hot Springs
country: United States
facility: St. Joseph'S Mercy Clinic
state: Arkansas
city: Sarasota
country: United States
facility: Sarasota Arthritis Research Center
state: Florida
city: Coeur D Alene
country: United States
facility: Coeur D'Alene Arthrit Clin
state: Idaho
city: Baltimore
country: United States
facility: Johns Hopkins University Division Of Rheumatology
state: Maryland
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Jackson
country: United States
facility: Arthritis Associates Of Mississippi
state: Mississippi
city: Lincoln
country: United States
facility: Physician Research Collaboration, Llc
state: Nebraska
city: Hickory
country: United States
facility: Piedmont Rheumatology, Pa
state: North Carolina
city: Wilmington
country: United States
facility: Carolina Arthritis Associates
state: North Carolina
city: Cleveland
country: United States
facility: Metrohealth Medical Center
state: Ohio
city: Middleburg
country: United States
facility: Isam A. Diab, Md
state: Ohio
city: Duncansville
country: United States
facility: Alan J. Kivitz, Md, Cpi
state: Pennsylvania
city: Orangeburg
country: United States
facility: Mitchell C. Feinman, Md
state: South Carolina
city: Glendale
country: United States
facility: Kurt Oelke, Md
state: Wisconsin
city: Cairns
country: Australia
facility: Local Institution
state: Queensland
city: Maroochydore
country: Australia
facility: Local Institution
state: Queensland
city: Woodville
country: Australia
facility: Local Institution
state: South Australia
city: Heidelberg
country: Australia
facility: Local Institution
state: Victoria
city: Malvern
country: Australia
facility: Local Institution
state: Victoria
city: Victoria Park
country: Australia
facility: Local Institution
state: Western Australia
city: Bruxelles
country: Belgium
facility: Local Institution
city: Kortrijk
country: Belgium
facility: Local Institution
city: Merksem
country: Belgium
facility: Local Institution
city: Calgary
country: Canada
facility: Local Institution
state: Alberta
city: Laval
country: Canada
facility: Local Institution
state: Quebec
city: Hjorring
country: Denmark
facility: Local Institution
city: Helsinki
country: Finland
facility: Local Institution
city: Tampere
country: Finland
facility: Local Institution
city: Chambray Les Tours
country: France
facility: Local Institution
city: Montpellier
country: France
facility: Local Institution
city: Paris Cedex 14
country: France
facility: Local Institution
city: Poitiers
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Hildesheim
country: Germany
facility: Local Institution
city: Muenchen
country: Germany
facility: Local Institution
city: Muenchen
country: Germany
facility: Local Institution
city: Muenchen
country: Germany
facility: Local Institution
city: Ancona
country: Italy
facility: Local Institution
city: Siena
country: Italy
facility: Local Institution
city: Daegu
country: Korea, Republic of
facility: Local Institution
city: Daejeon
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Metepec
country: Mexico
facility: Local Institution
state: Estado De Mexico
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Merida
country: Mexico
facility: Local Institution
state: Yucatan
city: Chihuahua
country: Mexico
facility: Local Institution
city: Queretaro
country: Mexico
facility: Local Institution
city: San Luis Potosi
country: Mexico
facility: Local Institution
city: Lublin
country: Poland
facility: Local Institution
city: Poznan
country: Poland
facility: Local Institution
city: Torun
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Wroc#aw
country: Poland
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Tver
country: Russian Federation
facility: Local Institution
city: Kempton Park
country: South Africa
facility: Local Institution
state: Gauteng
city: Pretoria
country: South Africa
facility: Local Institution
state: Gauteng
city: Pretoria
country: South Africa
facility: Local Institution
state: Gauteng
city: Pretoria
country: South Africa
facility: Local Institution
state: Gauteng
city: Durban
country: South Africa
facility: Local Institution
state: Kwa Zulu Natal
city: Panorama
country: South Africa
facility: Local Institution
state: Western Cape
city: Goteborg
country: Sweden
facility: Local Institution
city: Linkoping
country: Sweden
facility: Local Institution
city: Malmo
country: Sweden
facility: Local Institution
city: Stockholm
country: Sweden
facility: Local Institution
city: Uppsala
country: Sweden
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.