Rheumatoid ArthritisPhase 3AVERT-2NCT02504268
Effects of Abatacept in Patients With Early Rheumatoid Arthritis
A Phase 3 study testing Abatacept and Methotrexate in people with Rheumatoid Arthritis, run by Bristol-Myers Squibb at 201 sites in 31 countries.
Trial summary
The purpose of this study is to determine if abatacept is effective in the treatment of early rheumatoid arthritis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Abatacept and Methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 994 participants
- Where
- 201 sitesin 31 countries
- Study dates
- 3 Sep 2015to 19 Mar 2020
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Rheumatoid arthritis (RA) diagnosis less than 6 months
- CRP > 3 mg/L or Erythrocyte Sedimentation Rate (ESR) ≥ 28 mm/h
- At least 3 swollen and 3 tender joints
- Anti-citrullinated protein antibodies (ACPA) positive
Who cannot join
- At risk for tuberculosis
- Have acute infection
- Have chronic or recurrent bacterial or serious latent viral infection
- History of malignancies in the last 5 years except squamous skin, basal skin or cervical carcinoma
- Previous treatment with any conventional or biologic Disease-modifying anti rheumatic drugs (DMARD)
Trial locations and contacts
201 sites in 31 countries.
201 sites in 31 countries
United States42 sites
Albuquerque Center For Rheumatology
Albuquerque, New Mexico, 87102
Albuquerque Clinical Trials
Albuquerque, New Mexico, 87102
Arthritis Clinic Of Northern Virginia, P.C.
Arlington, Virginia, 22205
Joao Nascimento
Bridgeport, Connecticut, 06606
Coeur D'Alene Arthrit Clin
Coeur d'Alene, Idaho, 83814
Metroplex Clinical Research Center
Dallas, Texas, 75231
Spectrum Medical, Inc.
Danville, Virginia, 24541
Altoona Center For Clinical Research
Duncansville, Pennsylvania, 16635
St. Paul Rheumatology, P.A.
Eagan, Minnesota, 55121
Arthritis And Osteoporosis Associates, Pa
Freehold, New Jersey, 07728
St. Joseph Heritage Medical Group
Fullerton, California, 92835
Arizona Arthritis & Rheumatology Research PLLC
Glendale, Arizona, 85306
Rheumatic Disease Center
Glendale, Wisconsin, 53217
Klein And Associates, M.D., Pa
Hagerstown, Maryland, 21740
Local Institution
Hickory, North Carolina, 28601
CHI St. Vincent Medical Group Hot Springs
Hot Springs, Arkansas, 71913
Houston Institute For Clinical Research
Houston, Texas, 77074
Healthcare Partners Medical Group
Huntington Beach, California, 92646
Rheumatology Associates Of North Alabama, P.C.
Huntsville, Alabama, 35801
West Tennessee Research Institute
Jackson, Tennessee, 38305
Physician Research Collaboration, Llc
Lincoln, Nebraska, 68516
Arkansas Primary Care Clinic
Little Rock, Arkansas, 72204
Valerius Medical Group and Research Center
Los Alamitos, California, 90720
Arizona Arthritis & Rheumatology Research PLLC
Mesa, Arizona, 85210
Arthritis And Diabetes Clinic
Monroe, Louisiana, 71203
Hospital For Special Surgery
New York, New York, 10021-4892
Health Research Of Oklahoma
Oklahoma City, Oklahoma, 73103
Rheumatology Associates Of Central Florida, P.A.
Orlando, Florida, 32806
The Arthritis Group
Philadelphia, Pennsylvania, 19152
Arizona Arthritis & Rheumatology Research PLLC
Phoenix, Arizona, 85032
Arizona Arthritis & Rheumatology Research PLLC
Phoenix, Arizona, 85037
Pmg Research Of Salisbury
Salisbury, North Carolina, 28144
Arthritis Northwest
Spokane, Washington, 99204
Arthritis Consultants
St Louis, Missouri, 63141
Arizona Arthritis & Rheumatology Research PLLC
Sun City, Arizona, 85351
Tampa Medical Group, Pa
Tampa, Florida, 33614
Physicians Research Center, Llc
Toms River, New Jersey, 08755
Oklahoma Ctr For Arthritis Therapy And Research, Inc.
Tulsa, Oklahoma, 74104
Inland Rheumatology Clinical Trials Inc.
Upland, California, 91786
Carolina Arthritis Associates
Wilmington, North Carolina, 28401
Pmg Research Of Wilmington Llc
Wilmington, North Carolina, 28401
Clinical Research Center Of Reading, Llp
Wyomissing, Pennsylvania, 19610
Japan27 sites
Local Institution
Chuo-ku, Tokyo, 1048560
Local Institution
Fukuoka, Fukuoka, 8108563
Local Institution
Hamamatsu, Shizuoka, 4308558
Local Institution
Hiroshima, Hiroshima, 7348551
Local Institution
Hitachi-Naka, Ibaraki, 3120057
Local Institution
Iruma-gun, Saitama, 3500495
Local Institution
Isahaya-shi, Nagasaki, 8548501
Local Institution
Itabashi-ku, Tokyo, 1738610
Local Institution
Izumisano, Osaka, 5988577
Local Institution
Kagoshima, Kagoshima-ken, 8900063
Local Institution
Kato-shi, Hyōgo, 6731462
Local Institution
Kawachi-Nagano, Osaka, 5868521
Local Institution
Kawagoe-shi, Saitama, 3508550
Local Institution
Kitakyushu-shi, Fukuoka, 8078556
Local Institution
Meguro-ku, Tokyo, 1528902
Local Institution
Meguro-ku, Tokyo, 1538515
Local Institution
Mito, Ibaraki, 3100015
Local Institution
Nagoya, Aichi-ken, 4578511
Local Institution
Nagoya, Aichi-ken, 4668560
Local Institution
Sagamihara-shi, Kanagawa, 2520392
Local Institution
Sapporo, Hokkaido, 0608604
Local Institution
Sapporo, Hokkaido, 0608648
Local Institution
Sapporo, Hokkaido, 0630811
Local Institution
Sasebo-shi, Nagasaki, 8571195
Local Institution
Sayama-shi, Saitama, 3501305
Local Institution
Shinjuku-Ku, Tokyo, 1608582
Local Institution
Tomigusuku-shi, Okinawa, 9010224
Germany12 sites
Rheumapraxis Dr. Kurthen
Aachen, 52064
Charite Campus Mitte
Berlin, 10117
Rheumatologische Schwerpunktpraxis Dr. Zinke
Berlin, 13055
Immanuel Krankenhaus Berlin/Rheumaklinik Berlin Buch
Berlin, 13125
Schlosspark-Klinik
Berlin, 14059
Schwerpunktpraxis fuer Rheumatologie an den Kreiskliniken
Burghausen, 84489
Klinikum Der Albrecht-Ludwigs-Universitat
Freiburg im Breisgau, 79106
MVZ Rheuma
Hamburg, 20095
Hamburger Rheuma Forschungszentrum
Hamburg, 22391
Gemeinschaftspraxis Drs. von Hinueber u Demary
Hildesheim, 31134
Rheumatologie In Wuermtal
Planegg, 82152
Praxis Dr. Walter
Rendsburg, 24768
Argentina11 sites
Instituto De Rehabilitacion Psicofisica
Buenos Aires, 1428
Organizacion Medica De Investigacion S.A. (Omi)
Capital Federal, Buenos Aires, 1015
Local Institution
Ciudad Autonoma Beunos Aires, Buenos Aires, 1431
Hospital General De Agudos J.M. Ramos Mejia
Ciudad Autonoma de Buenos Aire, Buenos Aires, 1221
Centro Consultora Integral de Salud SRL
Córdoba, 5004
Hospital Privado-Centro Medico De Cordoba S.A.
Córdoba, 5016
Framingham Centro Medico
La Plata, Buenos Aires, 1902
Caici
Rosario, Santa Fe Province, 2000
Instituto de Asistencia Reumatologica Integral
San Fernando, Buenos Aires, 1646
Centro De Investigaciones Reumatologicas
San Miguel de Tucumán, 4000
Centro Medico Privado De Reumatologia
San Miguel de Tucumán, 4000
Mexico9 sites
Local Institution
Guadalajara, Jalisco, 44280
Local Institution
Guadalajara, Jalisco, 44600
Local Institution
Guadalajara, Jalisco
Local Institution
Guadalajara
Local Institution
León, Guanajuato, 37000
Local Institution
Mexicali, Estado de Baja California
Local Institution
Mexico City, Distrito Fededral, 11850
Local Institution
México D.F.
Local Institution
San Luis Potosí City, 78213
Brazil8 sites
Local Institution
Curitiba, Paraná, 80030-110
Local Institution
Juiz de Fora, Minas Gerais, 36010-570
Local Institution
Porto Alegre, Rio Grande do Sul, 90480-000
Local Institution
Santo André, São Paulo, 09060-870
Local Institution
São Paulo, 01228-200
Local Institution
São Paulo, 04032-060
Local Institution
São Paulo, 04266-010
Local Institution
Varginha, Minas Gerais, 37006-710
Poland7 sites
Nszoz Unica Cr
Dąbrówka, 62-069
Nzoz Mak Med
Nadarzyn, 05-830
SANUS Szpital Specjalistyczny Sp. z o.o.
Stalowa Wola, 37-450
Local Institution
Staszów, 28-200
Slaski Szpital Reumatologiczno - Rehabilitacyjny
Ustroń, 43-450
Instytut Reumatologii, I Klinika Reumatologii
Warsaw, 02637
Centrum Medyczne AMED Sp. z o.o.
Warsaw, 03-291
Hungary6 sites
Local Institution
Budapest, 1027
Belgyogy. Int. Reuma. DEOEC
Debrecen, 4032
Vaszary Kolos Hospital
Esztergom, 2500
Reumatologiai Osztaly Flor F.
Kistarcsa, 2143
Reumatologiai Osztaly MAV
Szolnok, 5000
Vital Medical Center
Veszprém, 8200
Italy6 sites
Ospedale Vittorio Emanuele
Catania, 95123
Istituto Gaetano Pini
Milan, 20122
Azienda Ospedaliera Luigi Sacco
Milan, 20154
Local Institution
Pavia, 27100
Local Institution
Roma, 00168
Ospedale Borgo Roma
Verona, 37134
Australia5 sites
Local Institution
Camberwell, Victoria, 3124
Local Institution
Coffs Harbour, 2450
Local Institution
Hobart, Tasmania, 7000
Local Institution
Maroochydore, Queensland, 4558
Local Institution
Southport, Queensland, 4215
Israel5 sites
Local Institution
Haifa, 31096
Local Institution
Petah Tikva, 4941492
Local Institution
Ramat Gan, 52621
Local Institution
Tel Litwinsky, 52620
Local Institution
Zrifin
Russia5 sites
Local Institution
Moscow, 119049
Local Institution
Saint Petersburg, 191124
Local Institution
Saint Petersburg, 197022
Local Institution
Yaroslavl, 150003
Local Institution
Yekaterinburg, 620102
South Africa5 sites
Local Institution
Cape Town, Western Cape, 7500
Local Institution
Pinelands, Cape Town, Western Cape, 7405
Local Institution
Port Elizabeth, Eastern Cape, 6045
Local Institution
Soweto, Gauteng, 2013
Local Institution
Stellenbosch, Western Cape, 7600
Spain5 sites
Local Institution
A Coruña, 15006
Local Institution
Barcelona, 08036
Local Institution
Madrid, 28006
Local Institution
Madrid, 28046
Local Institution
Santiago Compostela, 15702
Canada4 sites
Local Institution
Montreal, Quebec, H2L 1S6
Local Institution
Saskatchewan, Saskatchewan, S7K 0H6
Centre De Recherche Musculo-Squelettique
Trois-Rivières, Quebec, G8Z 1Y2
Local Institution
Winnipeg, Manitoba, R3A 1M3
Colombia4 sites
Centro de Investigacion en Reumatologia y Especialidades Medicas S.A.S
Bogotá
Fundacion Instituto de Reumatologia Fernando Chalem
Bogotá
Clinica de Artritis Temprana
Cali
Hospital Pablo Tobon Uribe
Medellín, MEDELLIN
Czechia4 sites
Oddeleni klinicke farmakologie
Plzen-Bory, 305 99
Revmatologicky ustav
Prague, 128 50
MEDICAL PLUS, s.r.o.
Uherské Hradiště, 686 01
PV Medical Services, s.r.o.
Zlín, 760 01
France4 sites
Local Institution
Lyon, 69437
Local Institution
Orléans, 45067
Local Institution
Poitiers, 86021
Local Institution
Toulouse, 31059
Peru4 sites
Local Institution
Lima, 27
Acq Medic Sac
Lima, LIMA 11
Clinica El Golf
Lima, Lima 27
Instituto De Ginecologia Y Reproduccion Inv. Clinical Sac
Lima, LIMA 33
Sweden4 sites
Local Institution
Gothenburg, 413 45
Local Institution
Malmö, 205 02
Local Institution
Stockholm, 171 76
Local Institution
Uppsala, 751 85
Taiwan4 sites
Local Institution
Tainan, 704
Local Institution
Taipei, 100
Local Institution
Taipei, 112
Local Institution
Taoyuan, 333
Chile3 sites
Centro De Estudios Reumatologicos
Santiago, Santiago Metropolitan, 7501126
Someal
Santiago, Santiago Metropolitan, 7510586
Centro Medico de Reumatologia Limitada
Temuco, Araucania, 4790928
Romania3 sites
Local Institution
Bucharest, 011192
Local Institution
Bucharest, 020983
Local Institution
Cluj-Napoca, 400006
South Korea3 sites
Local Institution
Anyang-si, Gyeonggi-do, 14068
Local Institution
Seongnam-si, Gyeonggi-do, 13620
Local Institution
Seoul, 04763
United Kingdom3 sites
Local Institution
Hull, HU3 2JZ
Local Institution
Leeds, North Yorkshire, LS7 4SA
Local Institution
Manchester, M13 9WL
Finland2 sites
Local Institution
Hyvinkää, 05800
Local Institution
Kuopio, 70110
Singapore2 sites
Local Institution
Singapore, 117549
Local Institution
Singapore, 169856
About this study
Official title: A Phase 3B, Randomized, Double-Blind Clinical Trial to Evaluate the Efficacy and Safety of Abatacept SC in Combination With Methotrexate Compared to Methotrexate Monotherapy in Achieving Clinical Remission in Adults With Early Rheumatoid Arthritis Who Are Methotrexate Naive
The purpose of this study is to determine if abatacept is effective in the treatment of early rheumatoid arthritis.
Read the detailed description
Subcutaneous (SC)
- Conditions
- Rheumatoid Arthritis
- Being tested
- Abatacept, Methotrexate, Abatacept Placebo, Methotrexate Placebo
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbataceptDrug
MethotrexateDrug
Abatacept PlaceboOther
Methotrexate PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| Combination Therapy: Abatacept + Methotrexate | Experimental | Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week Receives: Drug: Abatacept; Drug: Methotrexate |
| Methotrexate treatment | Active comparator | Methotrexate at least 15mg per week tablet or capsule orally Receives: Drug: Methotrexate |
| Abatacept Placebo | Placebo comparator | Placebo for Abatacept subcutaneous injection once per week Receives: Other: Abatacept Placebo |
| Methotrexate Placebo | Placebo comparator | Placebo to match Methotrexate capsule orally once per week Receives: Other: Methotrexate Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants in Simple Disease Activity Index (SDAI) Remission at Week 24
Simple Disease Activity Index (SDAI) is calculated using the following formula: TJC + SJC + PGA + MDGA + CRP (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) SDAI Remission is defined as SDAI <= 3.3.
Using a logistic regression model that includes treatment arm, randomization stratification factor, and baseline SDAI as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided. SDAI total score range: 0 to 86. SDAI <= 3.3 indicates disease remission and SDAI >26 = high disease activity.
Measured: Week 24
Secondary outcomes (4)
Percentage of Participants in Disease Activity Score (DAS)28 - C-reactive Protein (CRP) Remission at Week 24
DAS28-CRP = Disease Activity Score 28 based on C-reactive protein DAS28-CRP Remission is defined as DAS28-CRP <= 2.6 Using a logistic regression model that includes treatment arm, stratification variable and baseline measure as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided.
Measured: Week 24
Percentage of Participants in SDAI Remission at Week 52
Simple Disease Activity Index (SDAI) is calculated using the following formula: TJC + SJC + PGA + MDGA + CRP (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) SDAI Remission is defined as SDAI <= 3.3. Using a logistic regression model that includes treatment arm, randomization stratification factor, and baseline SDAI as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided. SDAI total score range: 0 to 86. SDAI <= 3.3 indicates disease remission and SDAI >26 = high disease activity.
Measured: Week 52
Mean Change From Baseline in Radiographic Progression of Joint Damage as Measured by Modified Sharp/Van Der Heijide Total Sharp Scores (TSS) at Week 52
The Modified Total Sharp Score (mTSS) is calculated as the bilateral sum of erosion and Joint Space Narrowing (JSN) scores across all joints of the hands and feet.The score range for mTSS is 0-448. Higher scores indicate more joint damage. The mean change from baseline in TSS using modified Sharp/van der Heijide scores was assessed using a rank-based nonparametric ANCOVA model.
Measured: Week 52
Percentage of Participants in Boolean Remission at Week 52
Boolean Remission is defined as Tender joint count less than 1, Swollen joint count less than 1, CRP less than 1 mg/dL, patient global assessment less than 1 (on 0 to 10 VAS scale). Logistic regression was used for this endpoint.
Measured: Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2015 (estimated)
- Study start3 Sep 2015
- Primary completion16 Jan 2017
- Study completion19 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 994 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02504268
- Sponsor's protocol ID
- IM101-550
- Other IDs
- 2015-001275-50, 2015
- Acronym
- AVERT-2
- Status last verified
- Jun 2021
- First submitted
- 20 Jul 2015
- Last updated
- 28 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Emery P, Fleischmann R, Wong R, Lozenski K, Tanaka Y, Bykerk V, Bingham CO 3rd, Huizinga TWJ, Citera G, Perera V, Murthy B, Maxwell KF, Passarell J, Hedrich WD, Williams D. Association Between Abatacept Exposure Levels and Infection Occurrence in Patients With Rheumatoid Arthritis: Post Hoc Analysis of the AVERT-2 Study. J Rheumatol. 2025 May 1;52(5):426-435. doi: 10.3899/jrheum.2024-0498.
PubMed 39814436Emery P, Tanaka Y, Bykerk VP, Bingham CO, Huizinga TWJ, Citera G, Huang KG, Wu C, Connolly SE, Elbez Y, Wong R, Lozenski K, Fleischmann R. The trajectory of clinical responses in patients with early rheumatoid arthritis who achieve sustained remission in response to abatacept: subanalysis of AVERT-2, a randomized phase IIIb study. Arthritis Res Ther. 2023 Apr 22;25(1):67. doi: 10.1186/s13075-023-03038-2.
PubMed 37087459Emery P, Tanaka Y, Bykerk VP, Huizinga TWJ, Citera G, Bingham CO 3rd, Banerjee S, Soule BP, Nys M, Connolly SE, Lozenski KL, Zhuo J, Wong R, Huang KG, Fleischmann R. Sustained Remission and Outcomes with Abatacept plus Methotrexate Following Stepwise Dose De-escalation in Patients with Early Rheumatoid Arthritis. Rheumatol Ther. 2023 Jun;10(3):707-727. doi: 10.1007/s40744-022-00519-9. Epub 2023 Mar 3.
PubMed 36869251Wu C, Hu Y, Schafer P, Connolly SE, Wong R, Nielsen SH, Bay-Jensen AC, Emery P, Tanaka Y, Bykerk VP, Bingham CO, Huizinga TW, Fleischmann R, Liu J. Baseline serum levels of cross-linked carboxy-terminal telopeptide of type I collagen predict abatacept treatment response in methotrexate-naive, anticitrullinated protein antibody-positive patients with early rheumatoid arthritis. RMD Open. 2022 Dec;8(2):e002683. doi: 10.1136/rmdopen-2022-002683.
PubMed 36585217