Clinical trial NCT00106522: A Study to Assess the Effect of Tocilizumab + Methotrexate on Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis Currently on Methotrexate Therapy
Official title: A Randomized, Double-blind Study of Safety and Reduction in Signs and Symptoms During Treatment With Tocilizumab Versus Placebo, in Combination With Methotrexate, in Patients With Moderate to Severe Active Rheumatoid Arthritis and Inadequate Response to Anti-TNF 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: 499
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 3 arm study will compare the safety and efficacy, with regard to reduction of signs and symptoms, of tocilizumab versus placebo in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis (RA) currently on MTX therapy, and who have had an inadequate response to prior therapy with an anti-tumor necrosis factor (anti-TNF) agent. Patients will be randomized to receive tocilizumab 4mg/kg iv, tocilizumab 8mg/kg or placebo iv, every 4 weeks. All patients will also receive methotrexate 10-25mg/week. The anticipated time on study treatment is 3-12 months, and the target sample size is 500+ individuals.


Eligibility criteria: Inclusion Criteria:

* adult 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 MTX;
* inadequate response or intolerance to treatment with 1 or more anti-TNF therapies within 1 year of entering study;
* on stable MTX 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 screening, or planned major surgery within 6 months after entering study;
* women who are pregnant or breast-feeding.

Primary outcomes:
measure: Percentage of patients with ACR 20 response
timeFrame: Week 24
measure: AEs, laboratory parameters, vital signs, ECGs.
timeFrame: Throughout study
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
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Scottsdale
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Hot Springs
country: United States
state: Arkansas
city: Little Rock
country: United States
state: Arkansas
city: Anaheim
country: United States
state: California
city: Fullerton
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Palm Desert
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Diego
country: United States
state: California
city: Santa Maria
country: United States
state: California
city: Torrance
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Aventura
country: United States
state: Florida
city: Boca Raton
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Palm Habor
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Tavares
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Zephyrhills
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Boise
country: United States
state: Idaho
city: Meridian
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Springfield
country: United States
state: Illinois
city: Springfield
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Bowling Green
country: United States
state: Kentucky
city: Elizabethtown
country: United States
state: Kentucky
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Portland
country: United States
state: Maine
city: Baltimore
country: United States
state: Maryland
city: Baltimore
country: United States
state: Maryland
city: Wheaton
country: United States
state: Maryland
city: Springfield
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Lansing
country: United States
state: Michigan
city: Duluth
country: United States
state: Minnesota
city: Rochester
country: United States
state: Minnesota
city: Tupelo
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: St Louis
country: United States
state: Missouri
city: Billings
country: United States
state: Montana
city: Missoula
country: United States
state: Montana
city: Las Vegas
country: United States
state: Nevada
city: Medford
country: United States
state: New Jersey
city: Mercerville
country: United States
state: New Jersey
city: Teaneck
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: Binghamton
country: United States
state: New York
city: Great Neck
country: United States
state: New York
city: Johnson City
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Orchard Park
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Chapel Hill
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Bismarck
country: United States
state: North Dakota
city: Canton
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Eugene
country: United States
state: Oregon
city: Bala Cynwyd
country: United States
state: Pennsylvania
city: Danville
country: United States
state: Pennsylvania
city: Duncansville
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Willow Grove
country: United States
state: Pennsylvania
city: Hickory
country: United States
state: South Carolina
city: Jackson
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Ogden
country: United States
state: Utah
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Salem
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Glendale
country: United States
state: Wisconsin
city: Malvern
country: Australia
city: Shenton Park
country: Australia
city: Sydney
country: Australia
city: Woolloongabba
country: Australia
city: Aalst
country: Belgium
city: Hasselt
country: Belgium
city: Merksem
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Winnipeg
country: Canada
state: Manitoba
city: Burlington
country: Canada
state: Ontario
city: Kitchener
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Mississauga
country: Canada
state: Ontario
city: Newmarket
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Amiens
country: France
city: Bordeaux
country: France
city: Le Kremlin Bicetre
country: France
city: Lille
country: France
city: Lyon
country: France
city: Nice
country: France
city: Paris
country: France
city: Paris
country: France
city: Strasbourg
country: France
city: Toulouse
country: France
city: Berlin
country: Germany
city: Dresden
country: Germany
city: Gommern
country: Germany
city: Herne
country: Germany
city: Köln
country: Germany
city: München
country: Germany
city: Wiesbaden
country: Germany
city: Wuerzburg
country: Germany
city: Reykjavik
country: Iceland
city: Brescia
country: Italy
city: Milano
country: Italy
city: Milano
country: Italy
city: Padova
country: Italy
city: Pavia
country: Italy
city: Pisa
country: Italy
city: Udine
country: Italy
city: Guadalajara
country: Mexico
city: Enschede
country: Netherlands
city: Nijmegen
country: Netherlands
city: Ponce
country: Puerto Rico
city: Jonkoping
country: Sweden
city: Karlstad
country: Sweden
city: Malmo
country: Sweden
city: Stockholm
country: Sweden
city: Lausanne
country: Switzerland
city: Basingstoke
country: United Kingdom
city: Bath
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Cannock
country: United Kingdom
city: Derby
country: United Kingdom
city: Lancaster
country: United Kingdom
city: Leeds
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Manchester
country: United Kingdom
city: Middlesborough
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Norwich
country: United Kingdom
city: Oxford
country: United Kingdom
city: Salford
country: United Kingdom
city: Southampton
country: United Kingdom
city: Stoke-on-trent
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Vieira MC, Zwillich SH, Jansen JP, Smiechowski B, Spurden D, Wallenstein GV. Tofacitinib Versus Biologic Treatments in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Tumor Necrosis Factor Inhibitors: Results From a Network Meta-analysis. Clin Ther. 2016 Dec;38(12):2628-2641.e5. doi: 10.1016/j.clinthera.2016.11.004. Epub 2016 Nov 24.
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: Strand V, Burmester GR, Ogale S, Devenport J, John A, Emery P. Improvements in health-related quality of life after treatment with tocilizumab in patients with rheumatoid arthritis refractory to tumour necrosis factor inhibitors: results from the 24-week randomized controlled RADIATE study. Rheumatology (Oxford). 2012 Oct;51(10):1860-9. doi: 10.1093/rheumatology/kes131. Epub 2012 Jun 28.
citation: Karsdal MA, Schett G, Emery P, Harari O, Byrjalsen I, Kenwright A, Bay-Jensen AC, Platt A. IL-6 receptor inhibition positively modulates bone balance in rheumatoid arthritis patients with an inadequate response to anti-tumor necrosis factor therapy: biochemical marker analysis of bone metabolism in the tocilizumab RADIATE study (NCT00106522). Semin Arthritis Rheum. 2012 Oct;42(2):131-9. doi: 10.1016/j.semarthrit.2012.01.004. Epub 2012 Mar 6.
citation: Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis. 2008 Nov;67(11):1516-23. doi: 10.1136/ard.2008.092932. Epub 2008 Jul 14.