A Study of Tocilizumab and Methotrexate Treatment Strategies (Adding Tocilizumab to Methotrexate Versus Switching to Tocilizumab) in Patients With Active Rheumatoid Arthritis With Inadequate Response to Prior Methotrexate Treatment
Randomized Placebo-controlled Study of Two Treatment Strategies Based on Tocilizumab (TCZ) With or Without Methotrexate (MTX) and Possible Addition of Other Disease-modifying Anti-rheumatic Drugs (DMARDs) in Patients...
2 other identifiers
interventional
556
18 countries
131
Brief Summary
This 2 arm study will compare 2 treatment strategies based on tocilizumab in combination with methotrexate or placebo in patients with moderate to severe rheumatoid arthritis. Patients receiving methotrexate treatment will be randomized to receive either a) tocilizumab 8 mg intravenous (iv) every 4 weeks + methotrexate orally (po) weekly or b) tocilizumab 8 mg iv every 4 weeks + placebo po weekly. After the first 24 weeks of blinded treatment, treatment adjustments (increase or decrease of treatment intensity) may be introduced at intervals, based on response. The anticipated time on study treatment is up to 3 years, and the target sample size is approximately 470 patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 rheumatoid-arthritis
Started Mar 2009
Typical duration for phase_3 rheumatoid-arthritis
131 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 16, 2008
CompletedFirst Posted
Study publicly available on registry
December 17, 2008
CompletedStudy Start
First participant enrolled
March 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2013
CompletedResults Posted
Study results publicly available
July 18, 2014
CompletedJuly 18, 2014
July 1, 2014
1.4 years
December 16, 2008
May 1, 2014
July 16, 2014
Conditions
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Disease Activity Score 28 Joints (DAS28) Remission at Week 24
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Week 24
Secondary Outcomes (35)
Percentage of Participants With American College of Rheumatology (ACR20) Response
Baseline, Weeks 24, 52, 104
Percentage of Participants With ACR50 Response
Baseline, Weeks 24, 52, 104
Percentage of Participants With ACR70 Response
Baseline, Weeks 24, 52, 104
Percentage of Participants With ACR90 Response
Baseline, Weeks 24, 52, 104
Time to First ACR20 Response
104 Weeks
- +30 more secondary outcomes
Study Arms (2)
Tocilizumab + Methotrexate
EXPERIMENTALTocilizumab 8 mg/kg (up to 800 mg) intravenous (IV) once every 4 weeks + weekly oral methotrexate continuing at the patient's pre-study dose for 24 weeks. Patients taking oral corticosteroids remained on their pre-study dose (up to 10 mg/day). Week 24 to Week 52 the dose of tocilizumab and methotrexate remained the same. Based on DAS28 assessments, corticosteroid dose was adjusted and disease-modifying antirheumatic drugs (DMARDS) added. Week 52 to Week 104, based on the DAS28 assessment, treatment was adjusted to one of four protocol specified treatment regimens: Treatment tapering, Continued treatment, Treatment intensification or Maintenance treatment. After Week 100, patients who discontinued tocilizumab because of remission were retreated with the last effective dose of tocilizumab or blinded methotrexate if a flare occurred.
Tocilizumab + Placebo
PLACEBO COMPARATORTocilizumab 8 mg/kg (up to 800 mg) IV once every 4 weeks + weekly oral placebo to methotrexate continuing at the patient's pre-study dose for 24 weeks. Patients taking oral corticosteroids remained on their pre-study dose (up to 10 mg/day). Week 24 to Week 52 the dose of tocilizumab and placebo to methotrexate remained the same. Based on DAS28 assessments, corticosteroid dose was adjusted and disease-modifying antirheumatic drug (DMARDS) added. Week 52 to Week 104, based on the DAS28 assessment, treatment was adjusted to one of four protocol specified treatment regimens: Treatment tapering, Continued treatment, Treatment intensification or Maintenance treatment. After Week 100, patients who discontinued tocilizumab because of remission were retreated with the last effective dose of tocilizumab or blinded placebo to methotrexate if a flare occurred.
Interventions
tocilizumab 8 mg IV every 4 weeks.
Approximately 15-17 mg methotrexate capsule orally once a week.
Eligibility Criteria
You may qualify if:
- adult patients, ≥ 18 years of age;
- moderate to severe active rheumatoid arthritis (Disease Activity Score (DAS28) \> 4.4);
- inadequate response to methotrexate;
- on a stable dose of ≥ 15mg/week methotrexate for at least 6 weeks.
You may not qualify if:
- prior treatment with a biologic;
- Rheumatoid arthritis (RA) functional class IV;
- known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections;
- evidence of active malignant disease.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (137)
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Santa Monica, California, 90404, United States
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Upland, California, 91786, United States
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Whittier, California, 90606, United States
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Aventura, Florida, 33180, United States
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Naples, Florida, 34102, United States
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Orange Park, Florida, 32073, United States
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Plantation, Florida, 33317, United States
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Sarasota, Florida, 34239, United States
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South Miami, Florida, 33143, United States
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Tamarac, Florida, 33321, United States
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Eagan, Minnesota, 55121, United States
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Las Vegas, Nevada, 89128, United States
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Mayfield, Ohio, 44143, United States
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Middleburg Heights, Ohio, 44130, United States
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Oklahoma City, Oklahoma, 73104, United States
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West Reading, Pennsylvania, 19611, United States
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Greenville, South Carolina, 29601, United States
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Nashville, Tennessee, 37205, United States
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Houston, Texas, 77004, United States
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San Antonio, Texas, 78217, United States
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Spokane, Washington, 99204, United States
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Belo Horizonte, Minas Gerais, 30130-100, Brazil
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Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
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São Paulo, São Paulo, 04026-000, Brazil
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São Paulo, São Paulo, 04039-004, Brazil
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São Paulo, São Paulo, 05403-000, Brazil
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Rijeka, 51000, Croatia
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Zagreb, 10000, Croatia
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Frederiksberg, 2000, Denmark
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Hellerup, 2900, Denmark
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Køge, 4600, Denmark
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Tallinn, 11312, Estonia
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Tallinn, 13419, Estonia
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Abbeville, 80142, France
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Boulogne-Billancourt, 92104, France
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Brest, 29609, France
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Échirolles, 38434, France
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Le Kremlin-Bicêtre, 94275, France
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Le Mans, 72037, France
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Marseille, 13285, France
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Marseille, 13385, France
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Monaco, 98012, France
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Nantes, 44035, France
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Nice, 06202, France
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Paris, 75571, France
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Paris, 75679, France
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Pierre-Bénite, 69495, France
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Vandœuvre-lès-Nancy, 54511, France
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Aachen, 52064, Germany
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Berlin, 10117, Germany
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Berlin, 13125, Germany
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Cologne, 50924, Germany
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Dresden, 01307, Germany
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Erlangen, 91054, Germany
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Hamburg, 22081, Germany
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Jena, 07747, Germany
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München, 80336, Germany
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Ratingen, 40882, Germany
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Würzburg, 97080, Germany
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Athens, 11527, Greece
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Thessaloniki, 54636, Greece
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Thessaloniki, 54642, Greece
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Afula, 18101, Israel
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Beersheba, 8410101, Israel
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Haifa, 31048, Israel
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Haifa, 34354, Israel
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Haifa, 34362, Israel
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Kfar Saba, 44281, Israel
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Ramat Gan, 52621, Israel
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Rishon LeZiyyon, Israel
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Tel Aviv, 6423906, Israel
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Ancona, 60020, Italy
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Bari, 70124, Italy
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Perugia, 06122, Italy
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Prato, 59100, Italy
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Roma, 00168, Italy
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Bauska, 3901, Latvia
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Daugavpils, 5417, Latvia
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Liepāja, 3400, Latvia
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Riga, 1006, Latvia
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Riga, 1038, Latvia
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Riga, LV-1002, Latvia
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Amsterdam, 1081 HV, Netherlands
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Amsterdam, 1105 AZ, Netherlands
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Leiden, 2333 ZA, Netherlands
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Maastricht, 6202 AZ, Netherlands
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Nijmegen, 6525 GA, Netherlands
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Utrecht, 3584 CX, Netherlands
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Drammen, 3004, Norway
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Gjettum, 1346, Norway
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Kristiansand, 4604, Norway
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Lillehammer, 2609, Norway
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Moss, 1535, Norway
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Oslo, 0319, Norway
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Bucharest, 011172, Romania
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Bucharest, 020983, Romania
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Barnaul, 656024, Russia
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Irkutsk, 664047, Russia
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Izhevsk, 426009, Russia
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Kazan', 420012, Russia
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Khanty-Mansiysk, 628011, Russia
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Kursk, 305007, Russia
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Moscow, 115522, Russia
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Novosibirsk, 630099, Russia
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Novosibirsk, 630117, Russia
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Saint Petersburg, 191015, Russia
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Tyumen, 625023, Russia
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Ufa, 450005, Russia
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Ulyanovsk, 432063, Russia
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Vladivostok, 690105, Russia
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Yekaterinburg, 620102, Russia
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Belgrade, 11000, Serbia
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Kragujevac, 34000, Serbia
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Niška Banja, 18250, Serbia
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Nova Sad, 21000, Serbia
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Barcelona, Barcelona, 08003, Spain
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A Coruña, La Coruña, 15006, Spain
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Santiago de Compostela, La Coruña, 15706, Spain
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Leganés, Madrid, 28191, Spain
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Madrid, Madrid, 28007, Spain
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Madrid, Madrid, 28041, Spain
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Madrid, Madrid, 28046, Spain
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Madrid, Madrid, 28222, Spain
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Oviedo, Principality of Asturias, 33006, Spain
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Seville, Sevilla, 41009, Spain
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Bilbao, Vizcaya, 48013, Spain
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Gothenburg, 41345, Sweden
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Umeå, 90185, Sweden
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Bangkok, 10300, Thailand
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Khon Kaen, 40002, Thailand
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Pathum Thani, 12120, Thailand
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Cannock, WS11 5XY, United Kingdom
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Glasgow, G12 0YN, United Kingdom
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Leeds, LS7 4SA, United Kingdom
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London, SE5 9RS, United Kingdom
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Newcastle upon Tyne, NE2 4HH, United Kingdom
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Norwich, NR4 7UY, United Kingdom
Related Publications (4)
Dougados M, Kissel K, Sheeran T, Tak PP, Conaghan PG, Mola EM, Schett G, Amital H, Navarro-Sarabia F, Hou A, Bernasconi C, Huizinga TW. Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis. 2013 Jan;72(1):43-50. doi: 10.1136/annrheumdis-2011-201282. Epub 2012 May 5.
PMID: 22562983RESULTDougados M, Kissel K, Conaghan PG, Mola EM, Schett G, Gerli R, Hansen MS, Amital H, Xavier RM, Troum O, Bernasconi C, Huizinga TW. Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study. Ann Rheum Dis. 2014 May;73(5):803-9. doi: 10.1136/annrheumdis-2013-204761. Epub 2014 Jan 28.
PMID: 24473673RESULTDougados M, Huizinga TW, Choy EH, Bingham CO 3rd, Aassi M, Bernasconi C. Evaluation of the Disease Activity Score in Twenty-Eight Joints-Based Flare Definitions in Rheumatoid Arthritis: Data From a Three-Year Clinical Trial. Arthritis Care Res (Hoboken). 2015 Dec;67(12):1762-6. doi: 10.1002/acr.22633.
PMID: 26037777DERIVEDHuizinga TW, Conaghan PG, Martin-Mola E, Schett G, Amital H, Xavier RM, Troum O, Aassi M, Bernasconi C, Dougados M. Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study. Ann Rheum Dis. 2015 Jan;74(1):35-43. doi: 10.1136/annrheumdis-2014-205752. Epub 2014 Aug 28.
PMID: 25169728DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffman-LaRoche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 16, 2008
First Posted
December 17, 2008
Study Start
March 1, 2009
Primary Completion
August 1, 2010
Study Completion
January 1, 2013
Last Updated
July 18, 2014
Results First Posted
July 18, 2014
Record last verified: 2014-07