Clinical trial NCT00106574: A Study to Assess the Effect of Tocilizumab + DMARD Therapy on Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis
Official title: A Randomized, Double-blind Study of the Effect of Tocilizumab on Reduction in Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis and Inadequate Response to DMARD Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2005-03-28
Enrollment: 1220
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 the safety and efficacy, with regard to reduction of signs and symptoms, of tocilizumab versus placebo in combination with traditional Disease-Modifying Anti-Rheumatic Drug (DMARD) therapy in patients with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to current DMARD therapy. Patients will be randomized to receive tocilizumab 8mg/kg iv or placebo iv every 4 weeks, in conjunction with stable DMARD therapy. The anticipated time on study treatment is 3-12 months, and the target sample size is 500+ individuals.


Eligibility criteria: Inclusion Criteria:

* patients at least 18 years of age with moderate to severe active RA for at least 6 months;
* inadequate response to current anti-rheumatic therapies, including 1 or more traditional DMARDs;
* stable DMARD therapy for at least 8 weeks before entering study;
* patients of reproductive potential must be using reliable methods of contraception.

Exclusion Criteria:

* major surgery (including joint surgery) within 8 weeks before entering study, or planned surgery within 6 months after entering study;
* patients who have previously failed treatment with an anti-tumor necrosis factor agent;
* women who are pregnant or breast-feeding.

Primary outcomes:
measure: Percentage of patients with ACR 20 response
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of patients with ACR 50 and ACR 70 responses.
timeFrame: Week 24
measure: Mean changes in parameters of ACR core set
timeFrame: Week 24
measure: AEs, laboratory parameters, vital signs.
timeFrame: Throughout study
Other outcomes:
Locations:
city: Mesa
country: United States
state: Arizona
city: Paradise Valley
country: United States
state: Arizona
city: Peoria
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Los Angeles
country: United States
state: California
city: Palm Desert
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: San Jose
country: United States
state: California
city: Upland
country: United States
state: California
city: Newark
country: United States
state: Delaware
city: Washington
country: United States
state: District of Columbia
city: Delray Beach
country: United States
state: Florida
city: Jupiter
country: United States
state: Florida
city: Palm Habor
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Springfield
country: United States
state: Illinois
city: Vernon Hills
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Bowling Green
country: United States
state: Kentucky
city: Baton Rouge
country: United States
state: Louisiana
city: Shreverport
country: United States
state: Louisiana
city: Frederick
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Lansing
country: United States
state: Michigan
city: Duluth
country: United States
state: Minnesota
city: Eagan
country: United States
state: Minnesota
city: St. Louis Park
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Springfield
country: United States
state: Missouri
city: Lincoln
country: United States
state: Nebraska
city: Reno
country: United States
state: Nevada
city: Clifton
country: United States
state: New Jersey
city: Haddon Heights
country: United States
state: New Jersey
city: New Brunswick
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: New York
country: United States
state: New York
city: Plainview
country: United States
state: New York
city: Roslyn
country: United States
state: New York
city: Smithtown
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Winston Salem
country: United States
state: North Carolina
city: Beachwood
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Gallipolis
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Medford
country: United States
state: Oregon
city: Allentown
country: United States
state: Pennsylvania
city: Bethlehem
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Rockledge
country: United States
state: Pennsylvania
city: Willow Grove
country: United States
state: Pennsylvania
city: Johnston
country: United States
state: Rhode Island
city: Charleston
country: United States
state: South Carolina
city: Hixson
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Mesquite
country: United States
state: Texas
city: Burlington
country: United States
state: Vermont
city: Arlington
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Vancouver
country: United States
state: Washington
city: La Crosse
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Rosario
country: Argentina
city: Parkville
country: Australia
city: Sydney
country: Australia
city: Campinas
country: Brazil
city: Goiania
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Winnipeg
country: Canada
state: Manitoba
city: Hamilton
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Quebec City
country: Canada
state: Quebec
city: Saskatoon
country: Canada
state: Saskatchewan
city: Beijing
country: China
city: Beijing
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: San Jose
country: Costa Rica
city: Hradec Kralove
country: Czech Republic
city: Praha
country: Czech Republic
city: Praha
country: Czech Republic
city: Helsinki
country: Finland
city: Jyväskylä
country: Finland
city: Boulogne-billancourt
country: France
city: Clermont-ferrand
country: France
city: Grenoble
country: France
city: Limoges
country: France
city: Marseille
country: France
city: Montpellier
country: France
city: Nantes
country: France
city: Paris
country: France
city: Pierre Benite
country: France
city: Rennes
country: France
city: Saint-etienne
country: France
city: Tours
country: France
city: Aachen
country: Germany
city: Essen
country: Germany
city: Hildesheim
country: Germany
city: München
country: Germany
city: Osnabrück
country: Germany
city: Sendenhorst
country: Germany
city: Stuttgart
country: Germany
city: Hong Kong
country: Hong Kong
city: Tuen Mun
country: Hong Kong
city: Leon
country: Mexico
city: Mexico City
country: Mexico
city: Mexico City
country: Mexico
city: Tijuana
country: Mexico
city: Panama City
country: Panama
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Ryazan
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Tula
country: Russian Federation
city: Durban
country: South Africa
city: Pretoria
country: South Africa
city: Radiokop
country: South Africa
city: Barakaldo
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Pontevedra
country: Spain
city: Santiago de Compostela
country: Spain
city: Stockholm
country: Sweden
city: Umea
country: Sweden
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Welsh P, Tuckwell K, McInnes IB, Sattar N. Effect of IL-6 receptor blockade on high-sensitivity troponin T and NT-proBNP in rheumatoid arthritis. Atherosclerosis. 2016 Nov;254:167-171. doi: 10.1016/j.atherosclerosis.2016.10.016. Epub 2016 Oct 8.
citation: Keystone EC, Anisfeld A, Ogale S, Devenport JN, Curtis JR. Continued benefit of tocilizumab plus disease-modifying antirheumatic drug therapy in patients with rheumatoid arthritis and inadequate clinical responses by week 8 of treatment. J Rheumatol. 2014 Feb;41(2):216-26. doi: 10.3899/jrheum.130489. Epub 2014 Jan 15.
citation: Wang J, Bansal AT, Martin M, Germer S, Benayed R, Essioux L, Lee JS, Begovich A, Hemmings A, Kenwright A, Taylor KE, Upmanyu R, Cutler P, Harari O, Marchini J, Criswell LA, Platt A. Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis. Pharmacogenomics J. 2013 Jun;13(3):235-41. doi: 10.1038/tpj.2012.8. Epub 2012 Apr 10.
citation: Genovese MC, McKay JD, Nasonov EL, Mysler EF, da Silva NA, Alecock E, Woodworth T, Gomez-Reino JJ. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum. 2008 Oct;58(10):2968-80. doi: 10.1002/art.23940.