Clinical trial NCT00810199: 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
Official title: 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...
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2008-12-17
Enrollment: 556
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants With Disease Activity Score 28 Joints (DAS28) Remission at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants With American College of Rheumatology (ACR20) Response
timeFrame: Baseline, Weeks 24, 52, 104
measure: Percentage of Participants With ACR50 Response
timeFrame: Baseline, Weeks 24, 52, 104
measure: Percentage of Participants With ACR70 Response
timeFrame: Baseline, Weeks 24, 52, 104
measure: Percentage of Participants With ACR90 Response
timeFrame: Baseline, Weeks 24, 52, 104
measure: Time to First ACR20 Response
timeFrame: 104 Weeks
measure: Time to First ACR50 Response
timeFrame: 104 Weeks
measure: Time to First ACR70 Response
timeFrame: 104 Weeks
measure: Time to First ACR90 Response
timeFrame: 104 Weeks
measure: Area Under Curve (AUC) DAS28
timeFrame: Baseline to Week 24
measure: Percentage of Participants With Disease Activity Score 28 (DAS28) Remission
timeFrame: Week 52
measure: Percentage of Participants With DAS28 Low Disease Activity (LDAS)
timeFrame: Weeks 24, 52
measure: Change From Baseline in DAS28 Score
timeFrame: Baseline, Weeks 24, 52
measure: Percentage of Participants With Good or Moderate European League (EULAR) DAS28 Responses
timeFrame: Baseline, 24, 52
measure: Change From Baseline in Swollen Joint Count
timeFrame: Baseline, Weeks 24, 52
measure: Change From Baseline in Tender Joint Count
timeFrame: Baseline, Weeks 24, 52
measure: Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (VAS)
timeFrame: Baseline, Weeks 24, 52
measure: Change From Baseline in Physician Global Assessment of Disease Activity Visual Analog Scale (VAS)
timeFrame: Baseline, Weeks 24, 52
measure: Change From Baseline in Patient Global Assessment of Pain (VAS)
timeFrame: Baseline, Weeks 24, 52
measure: Change From Baseline in Erythrocyte Sedimentation Rate (ESR)
timeFrame: Baseline, Weeks 24, 52
measure: Change From Baseline in C-Reactive Protein (CRP)
timeFrame: Baseline, Weeks 24, 52
measure: Change From Baseline in the Health Assessment Questionnaire Disability Index
timeFrame: Baseline, Weeks 24, 52
measure: Change From Baseline in Total Genant Modified Sharp Scores (GSS)
timeFrame: Baseline, Weeks 24, 52, 104
measure: Change From Baseline in Joint Space Narrowing Score
timeFrame: Baseline, Weeks 24, 52, 104
measure: Change From Baseline in Erosion Score
timeFrame: Baseline, Weeks 24, 52, 104
measure: Percentage of Participants Discontinuing Tocilizumab Due to Remission
timeFrame: Weeks 52, 104
measure: Percentage of Participants Who Withdrew Due to Lack of Sufficient Therapeutic Response
timeFrame: Up to 3 years
measure: Percentage of Participants Who Withdrew Due to Safety Reasons
timeFrame: Up to 3 years
measure: Change From Baseline in Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL)
timeFrame: Baseline, Weeks 24, 52, 104
measure: Change From Baseline in Academic Medical Center (AMC) Linear Disability Scale (ALDS)
timeFrame: Baseline, Weeks 104
measure: Area Under the Curve (AUC) From Baseline to Week 24 for ACR Response
timeFrame: Baseline to Week 24
measure: Area Under the Curve (AUC) From Baseline to Week 52 for ACR Response
timeFrame: Baseline to Week 52
measure: Time to Tocilizumab Remission
timeFrame: 104 Weeks
measure: Time to Drug-Free Remission
timeFrame: 104 Weeks
measure: Time to Flare After Tocilizumab Remission
timeFrame: 104 Weeks
measure: Time to Restart of Treatment After Discontinuation/Remission
timeFrame: 104 Weeks
Other outcomes:
Locations:
city: Santa Monica
country: United States
state: California
city: Upland
country: United States
state: California
city: Whittier
country: United States
state: California
city: Aventura
country: United States
state: Florida
city: Naples
country: United States
state: Florida
city: Orange Park
country: United States
state: Florida
city: Plantation
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: South Miami
country: United States
state: Florida
city: Tamarac
country: United States
state: Florida
city: Eagan
country: United States
state: Minnesota
city: Las Vegas
country: United States
state: Nevada
city: Mayfield
country: United States
state: Ohio
city: Middleburg Heights
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: West Reading
country: United States
state: Pennsylvania
city: Greenville
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Spokane
country: United States
state: Washington
city: Belo Horizonte
country: Brazil
state: MG
city: Porto Alegre
country: Brazil
state: RS
city: Sao Paulo
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Rijeka
country: Croatia
city: Zagreb
country: Croatia
city: Frederiksberg
country: Denmark
city: Hellerup
country: Denmark
city: Køge
country: Denmark
city: Tallinn
country: Estonia
city: Tallinn
country: Estonia
city: Abbeville
country: France
city: Boulogne-billancourt
country: France
city: Brest
country: France
city: Echirolles
country: France
city: Le Kremlin Bicetre
country: France
city: Le Mans
country: France
city: Marseille
country: France
city: Marseille
country: France
city: Monaco
country: France
city: Nantes
country: France
city: Nice
country: France
city: Paris
country: France
city: Paris
country: France
city: Pierre Benite
country: France
city: Vandoeuvre-les-nancy
country: France
city: Aachen
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Dresden
country: Germany
city: Erlangen
country: Germany
city: Hamburg
country: Germany
city: Jena
country: Germany
city: Köln
country: Germany
city: Muenchen
country: Germany
city: Ratingen
country: Germany
city: Wuerzburg
country: Germany
city: Athens
country: Greece
city: Thessaloniki
country: Greece
city: Thessaloniki
country: Greece
city: Afula
country: Israel
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Haifa
country: Israel
city: Haifa
country: Israel
city: Kfar Saba
country: Israel
city: Ramat-Gan
country: Israel
city: Rishon Lezion
country: Israel
city: Tel Aviv
country: Israel
city: Ancona
country: Italy
city: Bari
country: Italy
city: Perugia
country: Italy
city: Prato
country: Italy
city: Roma
country: Italy
city: Bauska
country: Latvia
city: Daugavpils
country: Latvia
city: Liepaja
country: Latvia
city: Riga
country: Latvia
city: Riga
country: Latvia
city: Riga
country: Latvia
city: Amsterdam
country: Netherlands
city: Amsterdam
country: Netherlands
city: Leiden
country: Netherlands
city: Maastricht
country: Netherlands
city: Nijmegen
country: Netherlands
city: Utrecht
country: Netherlands
city: Drammen
country: Norway
city: Gjettum
country: Norway
city: Kristiansand
country: Norway
city: Lillehammer
country: Norway
city: Moss
country: Norway
city: Oslo
country: Norway
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Barnaul
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Irkutsk
country: Russian Federation
city: Izhevsk
country: Russian Federation
city: Kazan
country: Russian Federation
city: Khanty-Mansiysk
country: Russian Federation
city: Kursk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Tjumen
country: Russian Federation
city: UFA
country: Russian Federation
city: Ulyanovsk
country: Russian Federation
city: Vladivostok
country: Russian Federation
city: Belgrade
country: Serbia
city: Kragujevac
country: Serbia
city: Niska Banja
country: Serbia
city: Nova sad
country: Serbia
city: Oviedo
country: Spain
state: Asturias
city: La Coruna
country: Spain
state: La Coruña
city: Santiago De Compostela
country: Spain
state: La Coruña
city: Leganes
country: Spain
state: Madrid
city: Bilbao
country: Spain
state: Vizcaya
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Goeteborg
country: Sweden
city: Umea
country: Sweden
city: Bangkok
country: Thailand
city: Khon Kaen
country: Thailand
city: Pathumthani
country: Thailand
city: Cannock
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Newcastle-upon-Tyne
country: United Kingdom
city: Norwich
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.