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

NCT ID: NCT00810199

Last Updated: 2014-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 556 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2013-01-31

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tocilizumab + Methotrexate

Tocilizumab 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.

Group Type: EXPERIMENTAL

tocilizumab [RoActemra/Actemra]

Intervention Type: DRUG

tocilizumab 8 mg IV every 4 weeks.

methotrexate

Intervention Type: DRUG

Approximately 15-17 mg methotrexate capsule orally once a week.

Tocilizumab + Placebo

Tocilizumab 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.

Group Type: PLACEBO_COMPARATOR

tocilizumab [RoActemra/Actemra]

Intervention Type: DRUG

tocilizumab 8 mg IV every 4 weeks.

placebo

Intervention Type: DRUG

Placebo matching methotrexate capsule taken orally once a week.

Interventions

tocilizumab [RoActemra/Actemra]

tocilizumab 8 mg IV every 4 weeks.

Intervention Type: DRUG

methotrexate

Approximately 15-17 mg methotrexate capsule orally once a week.

Intervention Type: DRUG

placebo

Placebo matching methotrexate capsule taken orally once a week.

Intervention Type: DRUG

Other Intervention Names

RoActemra/Actemra

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Santa Monica, California, United States

Upland, California, United States

Whittier, California, United States

Aventura, Florida, United States

Naples, Florida, United States

Orange Park, Florida, United States

Plantation, Florida, United States

Sarasota, Florida, United States

South Miami, Florida, United States

Tamarac, Florida, United States

Eagan, Minnesota, United States

Las Vegas, Nevada, United States

Mayfield, Ohio, United States

Middleburg Heights, Ohio, United States

Oklahoma City, Oklahoma, United States

West Reading, Pennsylvania, United States

Greenville, South Carolina, United States

Nashville, Tennessee, United States

Houston, Texas, United States

San Antonio, Texas, United States

Spokane, Washington, United States

Belo Horizonte, Minas Gerais, Brazil

Porto Alegre, Rio Grande do Sul, Brazil

São Paulo, São Paulo, Brazil

São Paulo, São Paulo, Brazil

São Paulo, São Paulo, Brazil

Rijeka, , Croatia

Zagreb, , Croatia

Frederiksberg, , Denmark

Hellerup, , Denmark

Køge, , Denmark

Tallinn, , Estonia

Tallinn, , Estonia

Abbeville, , France

Boulogne-Billancourt, , France

Brest, , France

Échirolles, , France

Le Kremlin-Bicêtre, , France

Le Mans, , France

Marseille, , France

Marseille, , France

Monaco, , France

Nantes, , France

Nice, , France

Paris, , France

Paris, , France

Pierre-Bénite, , France

Vandœuvre-lès-Nancy, , France

Aachen, , Germany

Berlin, , Germany

Berlin, , Germany

Cologne, , Germany

Dresden, , Germany

Erlangen, , Germany

Hamburg, , Germany

Jena, , Germany

München, , Germany

Ratingen, , Germany

Würzburg, , Germany

Athens, , Greece

Thessaloniki, , Greece

Thessaloniki, , Greece

Afula, , Israel

Beersheba, , Israel

Haifa, , Israel

Haifa, , Israel

Haifa, , Israel

Kfar Saba, , Israel

Ramat Gan, , Israel

Rishon LeZiyyon, , Israel

Tel Aviv, , Israel

Ancona, , Italy

Bari, , Italy

Perugia, , Italy

Prato, , Italy

Roma, , Italy

Bauska, , Latvia

Daugavpils, , Latvia

Liepāja, , Latvia

Riga, , Latvia

Riga, , Latvia

Riga, , Latvia

Amsterdam, , Netherlands

Amsterdam, , Netherlands

Leiden, , Netherlands

Maastricht, , Netherlands

Nijmegen, , Netherlands

Utrecht, , Netherlands

Drammen, , Norway

Gjettum, , Norway

Kristiansand, , Norway

Lillehammer, , Norway

Moss, , Norway

Oslo, , Norway

Bucharest, , Romania

Bucharest, , Romania

Barnaul, , Russia

Irkutsk, , Russia

Izhevsk, , Russia

Kazan', , Russia

Khanty-Mansiysk, , Russia

Kursk, , Russia

Moscow, , Russia

Novosibirsk, , Russia

Novosibirsk, , Russia

Saint Petersburg, , Russia

Tyumen, , Russia

Ufa, , Russia

Ulyanovsk, , Russia

Vladivostok, , Russia

Yekaterinburg, , Russia

Belgrade, , Serbia

Kragujevac, , Serbia

Niška Banja, , Serbia

Nova Sad, , Serbia

Barcelona, Barcelona, Spain

A Coruña, La Coruña, Spain

Santiago de Compostela, La Coruña, Spain

Leganés, Madrid, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Oviedo, Principality of Asturias, Spain

Seville, Sevilla, Spain

Bilbao, Vizcaya, Spain

Gothenburg, , Sweden

Umeå, , Sweden

Bangkok, , Thailand

Khon Kaen, , Thailand

Pathum Thani, , Thailand

Cannock, , United Kingdom

Glasgow, , United Kingdom

Leeds, , United Kingdom

London, , United Kingdom

Newcastle upon Tyne, , United Kingdom

Norwich, , United Kingdom

Countries

United States; Brazil; Croatia; Denmark; Estonia; France; Germany; Greece; Israel; Italy; Latvia; Netherlands; Norway; Romania; Russia; Serbia; Spain; Sweden; Thailand; United Kingdom

References

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.

Reference Type: RESULT

PMID: 22562983 (View on PubMed)

Dougados 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.

Reference Type: RESULT

PMID: 24473673 (View on PubMed)

Dougados 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.

Reference Type: DERIVED

PMID: 26037777 (View on PubMed)

Huizinga 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.

Reference Type: DERIVED

PMID: 25169728 (View on PubMed)

Other Identifiers

2008-001847-20

Identifier Type: -

Identifier Source: secondary_id

MA21488

Identifier Type: -

Identifier Source: org_study_id