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

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04909801
Collaborator
(none)
300
77
2
46
3.9
0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
300 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Sep 15, 2021
Anticipated Primary Completion Date :
Apr 3, 2023
Anticipated Study Completion Date :
Jul 17, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1: Abatacept + Methotrexate

Drug: Abatacept
Abatacept SC (125 mg) once weekly
Other Names:
  • BMS-188667
  • Orencia®
  • 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:
  • BMS-188667
  • Orencia®
  • Drug: Adalimumab
    Adalimumab SC (40 mg) once every 2 weeks
    Other Names:
  • Humira®
  • Drug: Methotrexate
    Methotrexate oral/parenteral maximum tolerated dose (minimum 15 mg and maximum 25 mg weekly)

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of shared epitope-positive (SE+) participants meeting 50% improvement in American College of Rheumatology criteria (ACR50) response [At week 24]

    Secondary Outcome Measures

    1. Proportion of SE+ participants achieving Disease Activity Score 28-joint count calculated using C-reactive protein (DAS28-CRP) remission (DAS28-CRP < 2.6) [At week 24]

    2. Proportion of whole study population participants meeting ACR50 response [At week 24]

    3. Proportion of SE+ participants achieving Clinical Disease Activity Index (CDAI) remission (CDAI ≤ 2.8) [At week 24]

    4. Mean change from baseline in SE+ participant-reported pain by visual analog scale (VAS) [At week 24]

    5. Proportion of SE+ subset achieving 20% improvement in American College of Rheumatology criteria (ACR20) responses [Up to 104 weeks]

    6. Proportion of SE+ whole population achieving ACR20 responses [Up to 104 weeks]

    7. Proportion of SE+ subset achieving 50% improvement in American College of Rheumatology criteria (ACR50) responses [Up to 104 weeks]

    8. Proportion of SE+ whole population achieving ACR50 responses [Up to 104 weeks]

    9. Proportion of SE+ subset achieving 70% improvement in American College of Rheumatology criteria (ACR70) responses [Up to 104 weeks]

    10. Proportion of SE+ whole population achieving ACR70 responses [Up to 104 weeks]

    11. Proportion of SE+ subset achieving Disease Activity Score (DAS) remission [Up to 104 weeks]

    12. Proportion of SE+ whole population achieving DAS remission [Up to 104 weeks]

    13. Proportion of SE+ subset achieving Clinical Disease Activity Index (CDAI) remission [Up to 104 weeks]

    14. Proportion of SE+ whole population achieving CDAI remission [Up to 104 weeks]

    15. Proportion of SE+ subset achieving Simple Disease Activity Index (SDAI) remission over the Single-blind Treatment Period (SBTP) [Up to 104 weeks]

    16. Proportion of SE+ subset achieving Simple Disease Activity Index (SDAI) remission over the Open-label Treatment Period (OLTP) [Up to 104 weeks]

    17. Proportion of SE+ whole population achieving SDAI remission over the SBTP [Up to 104 weeks]

    18. Proportion of SE+ whole population achieving SDAI remission over the OLTP [Up to 104 weeks]

    19. Mean changes from baseline in DAS28-CRP [Up to 104 weeks]

    20. Mean changes from baseline in CDAI [Up to 104 weeks]

    21. Mean changes from baseline in SDAI over the SBTP [Up to 104 weeks]

    22. Mean changes from baseline in SDAI over the OLTP [Up to 104 weeks]

    23. Mean changes from baseline in the 7 ACR core components over the SBTP [Up to 104 weeks]

    24. Mean changes from baseline in the 7 ACR core components over the OLTP [Up to 104 weeks]

    25. Mean change from baseline in 36-item Short Form Survey (SF-36) in SE+ subset at week 24 and week 104 [Up to 104 weeks]

    26. Mean change from baseline in SF-36 in SE+ whole population at week 24 and week 104 [Up to 104 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 St Joseph Heritage Healthcare-Rheumatology Fullerton California United States 92835
    2 Valerius Med Group & Res Ctr Of Greater Long Beach, Inc. Los Alamitos California United States 90720
    3 Barbara Davis Center for Childhood Diabetes-Rheumatology Aurora Colorado United States 80045
    4 Klein And Associates, M.D., Pa Cumberland Maryland United States 21502
    5 Klein & Associates, M.D., P.A. Hagerstown Maryland United States 21740
    6 Local Institution Saint Louis Missouri United States 63141
    7 Local Institution Lincoln Nebraska United States 68516
    8 Local Institution Freehold New Jersey United States 07728
    9 Carolina Arthritis Associates Wilmington North Carolina United States 28401
    10 Altoona Center For Clinical Research Duncansville Pennsylvania United States 16635
    11 West Tennessee Research Institute Jackson Tennessee United States 38305
    12 Metroplex Clinical Research Center Dallas Texas United States 75231
    13 Local Institution Glendale Wisconsin United States 53217
    14 Local Institution La Plata Buenos Aires Argentina 1900
    15 Local Institution - 0016 Quilmes Buenos Aires Argentina 1878
    16 Local Institution - 0014 San Isidro Buenos Aires Argentina 1642
    17 Local Institution - 0012 Caba Distrito Federal Argentina C1015
    18 Local Institution DQG Distrito Federal Argentina C1428
    19 Local Institution - 0057 San Miguel de Tucumán Tucuman Argentina T4000
    20 Local Institution - 0023 Buenos Aires Argentina 1428
    21 Local Institution - 0015 Buenos Aires Argentina 1431
    22 Local Institution - 0099 Cordoba Argentina 0
    23 Local Institution Botany New South Wales Australia 2019
    24 Local Institution - 0062 Paramatta New South Wales Australia 2150
    25 Local Institution Maroochydore Queensland Australia 4558
    26 Local Institution - 0102 Woodville South South Australia Australia 5001
    27 Local Institution - 0064 Camberwell Victoria Australia 3124
    28 Local Institution - 0065 Geelong Victoria Australia 3220
    29 Local Institution - 0105 Ivanhoe Victoria Australia 3079
    30 Local Institution - 0028 Brno Czechia 638 00
    31 Local Institution - 0025 Praha 2 Czechia 12850
    32 Local Institution - 0001 Montpellier France 34295
    33 Local Institution - 0047 Rouen France 76031
    34 CHU Strasbourg-Hautepierre-Service de Rhumatologie Strasbourg France 67098
    35 Local Institution - 0002 Toulouse France 31059
    36 Local Institution - 0059 Berlin Germany 10117
    37 Local Institution Bonn Germany 53127
    38 Local Institution - 0091 Freiburg Germany 79106
    39 Local Institution - 0053 Hamburg Germany 20095
    40 Local Institution - 0056 Planegg Germany 82152
    41 Local Institution - 0083 Catania Italy 95121
    42 Local Institution - 0077 Pavia Italy 27100
    43 Local Institution - 0078 Perugia Italy 06156
    44 Local Institution - 0100 Roma Italy 00168
    45 Local Institution - 0079 Kitakyushu Fukuoka Japan 807-8556
    46 Local Institution - 0110 Sapporo Hokkaido Japan 0608648
    47 Local Institution - 0046 Sendai-shi Miyagi Japan 980-8574
    48 Local Institution - 0112 Sasebo Nagasaki Japan 857-1195
    49 Local Institution - 0090 Kawagoe-shi Saitama Japan 3508550
    50 Local Institution Shinjuku-ku Tokyo Japan 1600016
    51 Local Institution - 0093 Aichi Japan 457-8511
    52 Local Institution - 0089 Tokyo Japan 104-8560
    53 Local Institution - 0006 Cdmx Distrito Federal Mexico 11850
    54 Local Institution - 0008 Mexico City Distrito Federal Mexico 14080
    55 Local Institution - 0017 Guadalajara Jalisco Mexico 44650
    56 Local Institution - 0117 Guadalajara Jalisco Mexico 44650
    57 Local Institution - 0118 San Luis Potosí SAN LUIS Potosi Mexico 78200
    58 Local Institution - 0005 Mérida Yucatán Mexico 97070
    59 Local Institution - 0009 Chihuahua Mexico 31000
    60 Local Institution - 0124 Bydgoszcz Poland 85-168
    61 Local Institution Bydgoszcz Poland 85-168
    62 Local Institution - 0019 Elblag Poland 82-300
    63 Local Institution - 0020 Torun Poland 87-100
    64 Local Institution - 0004 A Coruña Spain 15006
    65 Local Institution - 0003 Madrid Spain 28046
    66 Local Institution - 0085 Santander Spain 39008
    67 Local Institution - 0049 Basel Switzerland 4031
    68 Local Institution - 0052 St. Gallen Switzerland 9007
    69 Local Institution - 0098 Kaohsiung Niao Sung Dist Taiwan 83301
    70 Local Institution - 0104 New Taipei City Taiwan 220
    71 Local Institution - 0095 Taichung City Taiwan 402
    72 Local Institution - 0096 Taichung Taiwan 40447
    73 Local Institution - 0120 Tainan Taiwan 704
    74 Local Institution Tainan Taiwan 71004
    75 Local Institution - 0111 Cannock Staffordshire United Kingdom WS11 5XY
    76 Local Institution Greater London, London United Kingdom SE1 1UL
    77 Local Institution - 0060 Hull United Kingdom HU3 2JZ

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT04909801
    Other Study ID Numbers:
    • IM101-863
    • 2020-000350-96
    • U1111-1247-1367
    First Posted:
    Jun 2, 2021
    Last Update Posted:
    Aug 15, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Bristol-Myers Squibb
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 15, 2022