A Study to Compare the Response to Treatment With Abatacept vs Adalimumab, on Background Methotrexate, in Adults With Early, Seropositive, and Shared Epitope-positive Rheumatoid Arthritis and an Inadequate Response to Methotrexate

A Randomized, Head-to-head, Single-blind Study to Compare the Response to Treatment With Subcutaneous Abatacept vs Adalimumab, on Background Methotrexate, in Adults With Early, Seropositive Rheumatoid Arthritis Who Have "Shared Epitope" HLA Class II Risk Alleles and Have an Inadequate Response to Methotrexate

The purpose of this study is to evaluate the superiority in efficacy of abatacept compared with adalimumab, on background methotrexate, in adults with early, seropositive, and shared epitope-positive rheumatoid arthritis and an inadequate methotrexate response.

Study Overview

• Status: Active, not recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Abatacept; Drug: Methotrexate; Drug: Adalimumab

• Study Type: Interventional
• Enrollment (Actual): 338
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1428
    • Local Institution - 0023
  • Buenos Aires, Argentina, 1431
    • Local Institution - 0015
  • Buenos Aires, Argentina, 1428
    • Local Institution - 0022
  • Cordoba, Argentina
    • Local Institution - 0099
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1015ABO
      • Local Institution - 0012
    • Quilmes, Buenos Aires, Argentina, 1878
      • Local Institution - 0016
    • San Isidro, Buenos Aires, Argentina, 1642
      • Local Institution - 0014
  • Tucuman
    • San Miguel de Tucumán, Tucuman, Argentina, T4000
      • Local Institution - 0057
• Australia
  • New South Wales
    • Botany, New South Wales, Australia, 2019
      • Local Institution - 0072
    • Paramatta, New South Wales, Australia, 2150
      • Local Institution - 0062
  • Queensland
    • Maroochydore, Queensland, Australia, 4558
      • Local Institution - 0063
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • Local Institution - 0102
  • Victoria
    • Camberwell, Victoria, Australia, 3124
      • Local Institution - 0064
    • Geelong, Victoria, Australia, 3220
      • Local Institution - 0065
    • Ivanhoe, Victoria, Australia, 3079
      • Local Institution - 0105
• Czechia
  • Brno, Czechia, 638 00
    • Local Institution - 0028
  • Praha 2, Czechia, 12850
    • Local Institution - 0025
• France
  • Montpellier, France, 34295
    • Local Institution - 0001
  • Rouen, France, 76031
    • Local Institution - 0047
  • Strasbourg, France, 67098
    • Local Institution - 0035
  • Toulouse, France, 31059
    • Local Institution - 0002
• Germany
  • Berlin, Germany, 10117
    • Local Institution - 0059
  • Bonn, Germany, 53127
    • Local Institution - 0055
  • Freiburg, Germany, 79106
    • Local Institution - 0091
  • Hamburg, Germany, 20095
    • Local Institution - 0053
  • Planegg, Germany, 82152
    • Local Institution - 0056
• Italy
  • Catania, Italy, 95121
    • Local Institution - 0083
  • Pavia, Italy, 27100
    • Local Institution - 0077
  • Perugia, Italy, 06156
    • Local Institution - 0078
  • Roma, Italy, 00168
    • Local Institution - 0100
• Japan
  • Tokyo, Japan, 104-8560
    • Local Institution - 0089
  • Tokyo, Japan, 1600035
    • Local Institution - 0010
  • Aichi
    • Nagoya, Aichi, Japan, 457-8511
      • Local Institution - 0093
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 807-8556
      • Local Institution - 0079
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 0608648
      • Local Institution - 0110
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 980-8574
      • Local Institution - 0046
  • Nagasaki
    • Sasebo, Nagasaki, Japan, 857-1195
      • Local Institution - 0112
  • Saitama
    • Kawagoe, Saitama, Japan, 350-8550
      • Local Institution - 0090
• Mexico
  • Chihuahua, Mexico, 31000
    • Local Institution - 0009
  • Distrito Federal
    • Cdmx, Distrito Federal, Mexico, 11850
      • Local Institution - 0006
    • Mexico City, Distrito Federal, Mexico, 14080
      • Local Institution - 0008
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44650
      • Local Institution - 0017
    • Guadalajara, Jalisco, Mexico, 44650
      • Local Institution - 0117
  • SAN LUIS Potosi
    • San Luis Potosí, SAN LUIS Potosi, Mexico, 78200
      • Local Institution - 0118
  • Yucatán
    • Mérida, Yucatán, Mexico, 97070
      • Local Institution - 0005
• Poland
  • Bydgoszcz, Poland, 85-168
    • Local Institution - 0124
  • Elblag, Poland, 82-300
    • Local Institution - 0019
  • Kujawsko-pomorskie
    • Torun, Kujawsko-pomorskie, Poland, 87-100
      • Local Institution - 0020
• Spain
  • A Coruña, Spain, 15006
    • Local Institution - 0004
  • Madrid, Spain, 28046
    • Local Institution - 0003
  • Santander, Spain, 39008
    • Local Institution - 0085
• Switzerland
  • Basel, Switzerland, 4031
    • Local Institution - 0049
  • St. Gallen, Switzerland, 9007
    • Local Institution - 0052
• Taiwan
  • Kaohsiung Niao Sung Dist, Taiwan, 83301
    • Local Institution - 0098
  • New Taipei City, Taiwan, 220
    • Local Institution - 0104
  • Taichung, Taiwan, 40447
    • Local Institution - 0096
  • Taichung City, Taiwan, 402
    • Local Institution - 0095
  • Tainan, Taiwan, 704
    • Local Institution - 0120
• United Kingdom
  • Hull, United Kingdom, HU3 2JZ
    • Local Institution - 0060
  • London, United Kingdom, SE1 9RT
    • Local Institution - 0114
  • Staffordshire
    • Cannock, Staffordshire, United Kingdom, WS11 5XY
      • Local Institution - 0111
• United States
  • California
    • Fullerton, California, United States, 92835
      • Local Institution - 0036
    • Los Alamitos, California, United States, 90720
      • Local Institution - 0086
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Local Institution - 0041
  • Maryland
    • Cumberland, Maryland, United States, 21502
      • Local Institution - 0058
    • Hagerstown, Maryland, United States, 21740
      • Local Institution - 0038
  • Minnesota
    • Eagan, Minnesota, United States, 55121
      • Local Institution - 0084
  • New Jersey
    • Freehold, New Jersey, United States, 07728
      • Local Institution - 0040
  • New York
    • Brooklyn, New York, United States, 11201
      • NYU Langone Ambulatory Care Brooklyn Heights
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Local Institution - 0082
  • Oregon
    • Portland, Oregon, United States, 97239
      • Local Institution - 0127
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Local Institution - 0031
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Local Institution - 0034
  • Texas
    • Dallas, Texas, United States, 75231
      • Local Institution - 0044
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53217
      • Local Institution - 0119

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Early rheumatoid arthritis (RA), defined as symptoms of RA that started ≤ 12 months prior to screening and satisfied the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria for the classification of RA at some point during the 12-month period
• Naïve to any targeted (biologic or nonbiologic) disease-modifying antirheumatic drugs (DMARDs), conventional synthetic DMARDs other than methotrexate (MTX), or investigational therapies for RA
• Treated with MTX for at least 12 weeks, with a stable dose of oral or parenteral MTX for at least 4 weeks prior to randomization
• Anti-cyclic citrullinated peptide-2 (Anti-CCP-2) test that is > 3× the upper limit of normal and are positive for rheumatoid factor (RF) according to central lab testing during screening
• At least a Disease Activity Score 28-joint count calculated using C-reactive protein (DAS28-CRP) ≥ 3.2 at screening
• At least 3 tender and at least 3 swollen joints at screening and at randomization

Exclusion Criteria:

• Women who are breastfeeding
• Autoimmune disease other than RA (e.g., psoriasis, systemic lupus erythematosus [SLE], vasculitis, seronegative spondyloarthritis, inflammatory bowel disease, Sjogren's syndrome) or currently active fibromyalgia
• History of or current inflammatory joint disease other than RA (e.g., psoriatic arthritis, gout, reactive arthritis, Lyme disease)
• At risk for tuberculosis
• Recent acute infection
• History of chronic or recurrent bacterial infection (e.g., chronic pyelonephritis, osteomyelitis, bronchiectasis)
• History of infection of a joint prosthesis or artificial joint
• History of systemic fungal infections (such as histoplasmosis, blastomycosis, or coccidiomycosis)
• History of primary immunodeficiency
• Current clinical findings or a history of a demyelinating disorder
• 5 or more joints cannot be assessed for tenderness or swelling

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Abatacept + Methotrexate	Drug: Abatacept; Abatacept SC (125 mg) once weekly; Other Names: Orencia®; BMS-188667; Drug: Methotrexate; Methotrexate oral/parenteral maximum tolerated dose (minimum 15 mg and maximum 25 mg weekly)
Experimental: Arm 2: (Adalimumab + Methotrexate) followed by (Abatacept + Methotrexate)	Drug: Abatacept; Abatacept SC (125 mg) once weekly; Other Names: Orencia®; BMS-188667; Drug: Methotrexate; Methotrexate oral/parenteral maximum tolerated dose (minimum 15 mg and maximum 25 mg weekly); Drug: Adalimumab; Adalimumab SC (40 mg) once every 2 weeks; Other Names: Humira®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of SE+ Participants Meeting 50% Improvement in American College of Rheumatology Criteria (ACR50) Response at Week 24	The ACR 50 definition of improvement is a 50% improvement over baseline in tender and swollen joint counts (#1 and #2) and a 50% improvement in 3 of the 5 remaining core data set measures (Participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function, and acute phase reactant value). Baseline value is the last assessment taken prior to first dose of single-blind study medication.	Baseline, week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of SE+ Participants Achieving Disease Activity Score 28 Joint Count Calculated Using C Reactive Protein Remission (DAS28-CRP < 2.6) at Week 24	DAS28-CRP is a continuous variable which is a composite of 4 variables: the number of tender joints out of a pre-specified 28 joints, the number of swollen joints out of a pre-specified 28 joints, C-reactive protein in mg/L (CRP) and participant assessment of disease activity measure on a visual analogue scale (VAS) of 100mm. DAS28-CRP scores range from 0 to 10; higher scores indicate more active disease. DAS28-CRP is calculated using the following formula: DAS28-CRP(4) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96 where t28 = number of painful joints from 28 joints, sw28 = number of swollen joints from 28 joints, CRP = c-reactive protein in mg/L, and GH = general health or patient's global assessment of disease activity on a 100 mm VAS.	Week 24
Percentage of Participants Meeting 50% Improvement in American College of Rheumatology Criteria (ACR50) Response at Week 24	The ACR 50 definition of improvement is a 50% improvement over baseline in tender and swollen joint counts (#1 and #2) and a 50% improvement in 3 of the 5 remaining core data set measures (Participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function, and acute phase reactant value). Baseline value is the last assessment taken prior to first dose of single-blind study medication.	Baseline, week 24
Percentage of SE+ Participants Achieving Clinical Disease Activity Index Remission (CDAI <= 2.8) at Week 24	CDAI is a simple linear sum of the following four components: Tender joint counts out of 28 joints, Swollen joint counts out of 28 joints, Participant global assessment of disease activity (0-10cm), Physicians global assessment of disease activity (0-10cm). CDAI scores range from 2-76; higher scores indicate more active disease. CDAI is calculated using the following formula: TJC + SJC + PGA + MDGA where TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, and MDGA = physician global assessment on a visual analog scale 0-10 cm.	Week 24
Adjusted Mean Change From Baseline in SE+ Participant-Reported Pain Visual Analog Scale (VAS) at Week 24	Participant-reported pain by a 0-100mm visual analog scale; higher score indicates more pain. Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline = Post-baseline - Baseline value.	Baseline, week 24
Percentage of SE+ Participants Meeting 20% Improvement in American College of Rheumatology Criteria (ACR20) Response Over Time	The ACR 20 definition of improvement is a 20% improvement over baseline in tender and swollen joint counts (#1 and #2) and a 20% improvement in 3 of the 5 remaining core data set measures (Participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function, and acute phase reactant value). Baseline value is the last assessment taken prior to first dose of single-blind study medication.	Baseline, day 29, 57, 85, 113, 141, 169
Percentage of SE+ Participants Meeting 50% Improvement in American College of Rheumatology Criteria (ACR50) Response Over Time	The ACR 50 definition of improvement is a 50% improvement over baseline in tender and swollen joint counts (#1 and #2) and a 50% improvement in 3 of the 5 remaining core data set measures (Participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function, and acute phase reactant value). Baseline value is the last assessment taken prior to first dose of single-blind study medication.	Baseline, day 29, 57, 85, 113, 141, 169
Percentage of SE+ Participants Meeting 70% Improvement in American College of Rheumatology Criteria (ACR70) Response Over Time	The ACR 70 definition of improvement is a 70% improvement over baseline in tender and swollen joint counts (#1 and #2) and a 70% improvement in 3 of the 5 remaining core data set measures (Participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function, and acute phase reactant value). Baseline value is the last assessment taken prior to first dose of single-blind study medication.	Baseline, day 29, 57, 85, 113, 141, 169
Percentage of SE+ Participants Achieving Disease Activity Score 28 Joint Count Calculated Using C Reactive Protein Remission (DAS28-CRP < 2.6) Over Time	DAS28-CRP is a continuous variable which is a composite of 4 variables: the number of tender joints out of a pre-specified 28 joints, the number of swollen joints out of a pre-specified 28 joints, C-reactive protein in mg/L (CRP) and participant assessment of disease activity measure on a visual analogue scale (VAS) of 100mm. DAS28-CRP scores range from 0 to 10; higher scores indicate more active disease. DAS28-CRP is calculated using the following formula: DAS28-CRP(4) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96 where t28 = number of painful joints from 28 joints, sw28 = number of swollen joints from 28 joints, CRP = c-reactive protein in mg/L, and GH = general health or patient's global assessment of disease activity on a 100 mm VAS.	Day 29, 57, 85, 113, 141, 169
Percentage of SE+ Participants Achieving Clinical Disease Activity Index Remission (CDAI <= 2.8) Over Time	CDAI is a simple linear sum of the following four components: Tender joint counts out of 28 joints, Swollen joint counts out of 28 joints, Participant global assessment of disease activity (0-10cm), Physicians global assessment of disease activity (0-10cm). CDAI scores range from 2-76; higher scores indicate more active disease. CDAI is calculated using the following formula: TJC + SJC + PGA + MDGA where TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, and MDGA = physician global assessment on a visual analog scale 0-10 cm.	Day 29, 57, 85, 113, 141, 169
Percentage of SE+ Participants Achieving Simple Disease Activity Index Remission (SDAI <= 3.3) Over Time	SDAI is a simple linear sum of the following five components: Tender joint counts out of 28 joints, Swollen joint counts out of 28 joints, Participant global assessment of disease activity (0-10cm), Physicians global assessment of disease activity (0-10cm), high-sensitivity C-reactive protein (hsCRP mg/dL). SDAI total scores range from 0-86; higher scores indicate more active disease. SDAI is calculated using the following formula: TJC + SJC + PGA + MDGA + CRP where TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, MDGA = physician global assessment on a visual analog scale 0-10 cm, and CRP = c-reactive protein in mg/dL.	Day 29, 57, 85, 113, 141, 169
Percentage of Participants Meeting 20% Improvement in American College of Rheumatology Criteria (ACR20) Response Over Time	The ACR 20 definition of improvement is a 20% improvement over baseline in tender and swollen joint counts (#1 and #2) and a 20% improvement in 3 of the 5 remaining core data set measures (Participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function, and acute phase reactant value). Baseline value is the last assessment taken prior to first dose of single-blind study medication.	Baseline, day 29, 57, 85, 113, 141, 169
Percentage of Participants Meeting 50% Improvement in American College of Rheumatology Criteria (ACR50) Response Over Time	The ACR 50 definition of improvement is a 50% improvement over baseline in tender and swollen joint counts (#1 and #2) and a 50% improvement in 3 of the 5 remaining core data set measures (Participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function, and acute phase reactant value). Baseline value is the last assessment taken prior to first dose of single-blind study medication.	Baseline, day 29, 57, 85, 113, 141, 169
Percentage of Participants Meeting 70% Improvement in American College of Rheumatology Criteria (ACR70) Response Over Time	The ACR 70 definition of improvement is a 70% improvement over baseline in tender and swollen joint counts (#1 and #2) and a 70% improvement in 3 of the 5 remaining core data set measures (Participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function, and acute phase reactant value). Baseline value is the last assessment taken prior to first dose of single-blind study medication.	Baseline, day 29, 57, 85, 113, 141, 169
Percentage of Participants Achieving Disease Activity Score 28 Joint Count Calculated Using C Reactive Protein Remission (DAS28-CRP < 2.6) Over Time	DAS28-CRP is a continuous variable which is a composite of 4 variables: the number of tender joints out of a pre-specified 28 joints, the number of swollen joints out of a pre-specified 28 joints, C-reactive protein in mg/L (CRP) and participant assessment of disease activity measure on a visual analogue scale (VAS) of 100mm. DAS28-CRP scores range from 0 to 10; higher scores indicate more active disease. DAS28-CRP is calculated using the following formula: DAS28-CRP(4) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96 where t28 = number of painful joints from 28 joints, sw28 = number of swollen joints from 28 joints, CRP = c-reactive protein in mg/L, and GH = general health or patient's global assessment of disease activity on a 100 mm VAS.	Day 29, 57, 85, 113, 141, 169
Percentage of Participants Achieving Clinical Disease Activity Index Remission (CDAI <= 2.8) Over Time	CDAI is a simple linear sum of the following four components: Tender joint counts out of 28 joints, Swollen joint counts out of 28 joints, Participant global assessment of disease activity (0-10cm), Physicians global assessment of disease activity (0-10cm). CDAI scores range from 2-76; higher scores indicate more active disease. CDAI is calculated using the following formula: TJC + SJC + PGA + MDGA where TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, and MDGA = physician global assessment on a visual analog scale 0-10 cm.	Day 29, 57, 85, 113, 141, 169
Percentage of Participants Achieving Simple Disease Activity Index Remission (SDAI <= 3.3) Over Time	SDAI is a simple linear sum of the following five components: Tender joint counts out of 28 joints, Swollen joint counts out of 28 joints, Participant global assessment of disease activity (0-10cm), Physicians global assessment of disease activity (0-10cm), high-sensitivity C-reactive protein (hsCRP mg/dL). SDAI total scores range from 0-86; higher scores indicate more active disease. SDAI is calculated using the following formula: TJC + SJC + PGA + MDGA + CRP where TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, MDGA = physician global assessment on a visual analog scale 0-10 cm, and CRP = c-reactive protein in mg/dL.	Day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in Disease Activity Score 28 Joint Count Calculated Using C Reactive Protein (DAS28-CRP) Over Time for SE+ Participants	DAS28-CRP is a continuous variable which is a composite of 4 variables: the number of tender joints out of a pre-specified 28 joints, the number of swollen joints out of a pre-specified 28 joints, C-reactive protein in mg/L (CRP) and participant assessment of disease activity measure on a visual analogue scale (VAS) of 100mm. DAS28-CRP scores range from 0 to 10; higher scores indicate more active disease. Remission was defined as DAS28-CRP < 2.6. DAS28-CRP is calculated using the following formula: DAS28-CRP(4) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96 where t28 = number of painful joints from 28 joints, sw28 = number of swollen joints from 28 joints, CRP = c-reactive protein in mg/L, and GH = general health or patient's global assessment of disease activity on a 100 mm VAS. Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline = Post-baseline - Baseline value.	Baseline, day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in Clinical Disease Activity Index (CDAI) Over Time for SE+ Participants	CDAI is a simple linear sum of the following four components: Tender joint counts out of 28 joints, Swollen joint counts out of 28 joints, Participant global assessment of disease activity (0-10cm), Physicians global assessment of disease activity (0-10cm). CDAI scores range from 2-76; higher scores indicate more active disease. CDAI remission was defined as =<2.8. CDAI is calculated using the following formula: TJC + SJC + PGA + MDGA where TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, and MDGA = physician global assessment on a visual analog scale 0-10 cm. Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline = Post-baseline - Baseline value.	Baseline, day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in Simple Disease Activity Index (SDAI) Over Time for SE+ Participants	SDAI is a simple linear sum of the following five components: Tender joint counts out of 28 joints, Swollen joint counts out of 28 joints, Participant global assessment of disease activity (0-10cm), Physicians global assessment of disease activity (0-10cm), high-sensitivity C-reactive protein (hsCRP mg/dL). SDAI total scores range from 0-86; higher scores indicate more active disease. Remission was defined as SDAI =< 3.3. SDAI is calculated using the following formula: TJC + SJC + PGA + MDGA + CRP where TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, MDGA = physician global assessment on a visual analog scale 0-10 cm, and CRP = c-reactive protein in mg/dL. Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline = Post-baseline - Baseline value.	Baseline, day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in American College of Rheumatology (ACR) Core Components 3-5 Over Time for SE+ Participants	Tender joint count (standard 68 joint count); Swollen joint count (standard 66 joint count); Participant global assessment of pain (a 0-100mm visual analog scale with 100 mm being the worst pain); Participant global assessment of disease activity (a 0-100mm visual analog scale with 100 mm being the highest disease activity); Physician global assessment of disease activity (a 0-100mm visual analog scale with 100 mm being the worst case); Participant assessment of physical function Health Assessment Questionnaire Disability Index (HAQ-DI) (increasing scores for the 8 disability categories indicate increasing level of difficulty). HAQDI is calculated by summing the adjusted categories scores and dividing by the number of categories answered; C-reactive protein (increasing levels indicate increasing level of disease) Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline=Post-baseline - Baseline value.	Baseline, day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in American College of Rheumatology (ACR) Core Components 1-2 Over Time for SE+ Participants	Tender joint count (standard 68 joint count); Swollen joint count (standard 66 joint count); Participant global assessment of pain (a 0-100mm visual analog scale with 100 mm being the worst pain); Participant global assessment of disease activity (a 0-100mm visual analog scale with 100 mm being the highest disease activity); Physician global assessment of disease activity (a 0-100mm visual analog scale with 100 mm being the worst case); Participant assessment of physical function Health Assessment Questionnaire Disability Index (HAQ-DI) (increasing scores for the 8 disability categories indicate increasing level of difficulty). HAQDI is calculated by summing the adjusted categories scores and dividing by the number of categories answered; C-reactive protein (increasing levels indicate increasing level of disease) Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline=Post-baseline - Baseline value.	Baseline, day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in American College of Rheumatology (ACR) Core Components 6 Over Time for SE+ Participants	6) Participant assessment of physical function Health Assessment Questionnaire Disability Index (HAQ-DI). For the eight disability categories (Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities), there is an aids or devices variables to record the type of assistance. If aids or devices and/or assistance from another person are checked for a category, the score is set to 2 (much difficulty), if the original score is 0 (no difficulty) or 1 (some difficulty). HAQ-DI is then calculated by summing the adjusted categories scores and dividing by the number of categories answered (increasing scores for the 8 disability categories questionnaire indicate increasing level of difficulty with 0 being the lowest score "without any difficulty" and 3 being the highest score "unable to do". Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline=Post-baseline - Baseline value.	Baseline, day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in American College of Rheumatology (ACR) Core Components 7 Over Time for SE+ Participants	Tender joint count (standard 68 joint count); Swollen joint count (standard 66 joint count); Participant global assessment of pain (a 0-100mm visual analog scale with 100 mm being the worst pain); Participant global assessment of disease activity (a 0-100mm visual analog scale with 100 mm being the highest disease activity); Physician global assessment of disease activity (a 0-100mm visual analog scale with 100 mm being the worst case); Participant assessment of physical function Health Assessment Questionnaire Disability Index (HAQ-DI) (increasing scores for the 8 disability categories indicate increasing level of difficulty). HAQDI is calculated by summing the adjusted categories scores and dividing by the number of categories answered; C-reactive protein (increasing levels indicate increasing level of disease) Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline=Post-baseline - Baseline value.	Baseline, day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in Disease Activity Score 28 Joint Count Calculated Using C Reactive Protein (DAS28-CRP) Over Time for All Participants	DAS28-CRP is a continuous variable which is a composite of 4 variables: the number of tender joints out of a pre-specified 28 joints, the number of swollen joints out of a pre-specified 28 joints, C-reactive protein in mg/L (CRP) and participant assessment of disease activity measure on a visual analogue scale (VAS) of 100mm. DAS28-CRP scores range from 0 to 10; higher scores indicate more active disease. Remission was defined as DAS28-CRP < 2.6. DAS28-CRP is calculated using the following formula: DAS28-CRP(4) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96 where t28 = number of painful joints from 28 joints, sw28 = number of swollen joints from 28 joints, CRP = c-reactive protein in mg/L, and GH = general health or patient's global assessment of disease activity on a 100 mm VAS. Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline = Post-baseline - Baseline value.	Baseline, day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in Clinical Disease Activity Index (CDAI) Over Time for All Participants	CDAI is a simple linear sum of the following four components: Tender joint counts out of 28 joints, Swollen joint counts out of 28 joints, Participant global assessment of disease activity (0-10cm), Physicians global assessment of disease activity (0-10cm). CDAI scores range from 2-76; higher scores indicate more active disease. CDAI remission was defined as =<2.8. CDAI is calculated using the following formula: TJC + SJC + PGA + MDGA where TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, and MDGA = physician global assessment on a visual analog scale 0-10 cm. Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline = Post-baseline - Baseline value.	Baseline, day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in Simple Disease Activity Index (SDAI) Over Time for All Participants	SDAI is a simple linear sum of the following five components: Tender joint counts out of 28 joints, Swollen joint counts out of 28 joints, Participant global assessment of disease activity (0-10cm), Physicians global assessment of disease activity (0-10cm), high-sensitivity C-reactive protein (hsCRP mg/dL). SDAI total scores range from 0-86; higher scores indicate more active disease. Remission was defined as SDAI =< 3.3. SDAI is calculated using the following formula: TJC + SJC + PGA + MDGA + CRP where TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, MDGA = physician global assessment on a visual analog scale 0-10 cm, and CRP = c-reactive protein in mg/dL. Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline = Post-baseline - Baseline value.	Baseline, day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in American College of Rheumatology (ACR) Core Components 3-5 Over Time for All Participants	Tender joint count (standard 68 joint count); Swollen joint count (standard 66 joint count); Participant global assessment of pain (a 0-100mm visual analog scale with 100 mm being the worst pain); Participant global assessment of disease activity (a 0-100mm visual analog scale with 100 mm being the highest disease activity); Physician global assessment of disease activity (a 0-100mm visual analog scale with 100 mm being the worst case); Participant assessment of physical function Health Assessment Questionnaire Disability Index (HAQ-DI) (increasing scores for the 8 disability categories indicate increasing level of difficulty). HAQDI is calculated by summing the adjusted categories scores and dividing by the number of categories answered; C-reactive protein (increasing levels indicate increasing level of disease) Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline=Post-baseline - Baseline value.	Baseline, day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in American College of Rheumatology (ACR) Core Components 1-2 Over Time for All Participants	Tender joint count (standard 68 joint count); Swollen joint count (standard 66 joint count); Participant global assessment of pain (a 0-100mm visual analog scale with 100 mm being the worst pain); Participant global assessment of disease activity (a 0-100mm visual analog scale with 100 mm being the highest disease activity); Physician global assessment of disease activity (a 0-100mm visual analog scale with 100 mm being the worst case); Participant assessment of physical function Health Assessment Questionnaire Disability Index (HAQ-DI) (increasing scores for the 8 disability categories indicate increasing level of difficulty). HAQDI is calculated by summing the adjusted categories scores and dividing by the number of categories answered; C-reactive protein (increasing levels indicate increasing level of disease) Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline=Post-baseline - Baseline value.	Baseline, day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in American College of Rheumatology (ACR) Core Components 6 Over Time for All Participants	6) Participant assessment of physical function Health Assessment Questionnaire Disability Index (HAQ-DI). For the eight disability categories (Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities), there is an aids or devices variables to record the type of assistance. If aids or devices and/or assistance from another person are checked for a category, the score is set to 2 (much difficulty), if the original score is 0 (no difficulty) or 1 (some difficulty). HAQ-DI is then calculated by summing the adjusted categories scores and dividing by the number of categories answered (increasing scores for the 8 disability categories questionnaire indicate increasing level of difficulty with 0 being the lowest score "without any difficulty" and 3 being the highest score "unable to do". Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline=Post-baseline - Baseline value.	Baseline, day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in American College of Rheumatology (ACR) Core Components 7 Over Time for All Participants	Tender joint count (standard 68 joint count); Swollen joint count (standard 66 joint count); Participant global assessment of pain (a 0-100mm visual analog scale with 100 mm being the worst pain); Participant global assessment of disease activity (a 0-100mm visual analog scale with 100 mm being the highest disease activity); Physician global assessment of disease activity (a 0-100mm visual analog scale with 100 mm being the worst case); Participant assessment of physical function Health Assessment Questionnaire Disability Index (HAQ-DI) (increasing scores for the 8 disability categories indicate increasing level of difficulty). HAQDI is calculated by summing the adjusted categories scores and dividing by the number of categories answered; C-reactive protein (increasing levels indicate increasing level of disease) Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline=Post-baseline - Baseline value.	Baseline, day 29, 57, 85, 113, 141, 169
Adjusted Mean Change From Baseline in 36-item Short Form Survey (SF-36) Over Time for SE+ Participants	SF-36 is a generic 36-item questionnaire measuring health-related quality of life, which covers 8 health dimensions within 2 components. The physical component summary (PCS) consists of these 4 subscales: Physical functioning, Role-physical, Bodily pain, General health. The mental component summary (MCS) consists of these 4 subscales: Vitality, Social functioning, Role-emotional, Mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100, with a higher score indicating better quality of life. The 8 subscales will be scored using norm-based methods that have standardized the T-scores to a mean of 50 and a standard deviation of 10 in the general population.	Up to week 24
Adjusted Mean Change From Baseline in SF-36 Over Time for All Participants	SF-36 is a generic 36-item questionnaire measuring health-related quality of life, which covers 8 health dimensions within 2 components. The physical component summary (PCS) consists of these 4 subscales: Physical functioning, Role-physical, Bodily pain, General health. The mental component summary (MCS) consists of these 4 subscales: Vitality, Social functioning, Role-emotional, Mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100, with a higher score indicating better quality of life. The 8 subscales will be scored using norm-based methods that have standardized the T-scores to a mean of 50 and a standard deviation of 10 in the general population.	Up to week 24
Adjusted Mean Change From Baseline in 36-item Short Form Survey (SF-36) at Week 104 for SE+ Participants	The SF-36 v2.0, which covers 8 health dimensions within 2 components. The physical component summary (PCS) of the SF-36 consists of these 4 subscales: Physical functioning, Role-physical, Bodily pain, General health. The mental component summary (MCS) of the SF-36 consists of these 4 subscales: Vitality, Social functioning, Role-emotional, Mental health. The scores range from 0 to 100, with a higher score indicating better quality of life. The 2 summary scores (PCS and MCS) will be calculated by taking a weighted linear combination of the 8 individual subscales. Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline = Post-baseline - Baseline value.	Up to week 24
Adjusted Mean Change From Baseline in 36-item Short Form Survey (SF-36) at Week 104 for All Participants	The SF-36 v2.0, which covers 8 health dimensions within 2 components. The physical component summary (PCS) of the SF-36 consists of these 4 subscales: Physical functioning, Role-physical, Bodily pain, General health. The mental component summary (MCS) of the SF-36 consists of these 4 subscales: Vitality, Social functioning, Role-emotional, Mental health. The scores range from 0 to 100, with a higher score indicating better quality of life. The 2 summary scores (PCS and MCS) will be calculated by taking a weighted linear combination of the 8 individual subscales. Baseline value is the last assessment taken prior to first dose of single-blind study medication. Change from Baseline = Post-baseline - Baseline value.	Up to week 24

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Actual): June 14, 2023
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: May 28, 2021
• First Submitted That Met QC Criteria: May 28, 2021
• First Posted (Actual): June 2, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Methotrexate; Rheumatoid Arthritis; Abatacept; Adalimumab; Humira®; BMS-188667; Orencia®
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Arthritis, Rheumatoid; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Tumor Necrosis Factor Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Enzyme Inhibitors; Antirheumatic Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Antimetabolites, Antineoplastic; Antimetabolites; Dermatologic Agents; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Adalimumab; Abatacept; Methotrexate
• Other Study ID Numbers: IM101-863; 2020-000350-96 (EudraCT Number); U1111-1247-1367 (Registry Identifier: WHO)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No