Clinical trial NCT00106548: A Study to Assess the Effect of Tocilizumab + Methotrexate on Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis
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 Rheumatoid Arthritis
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: 623
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, both in combination with methotrexate (MTX). in patients with moderate to severe active rheumatoid arthritis (RA) who currently have an inadequate response to MTX. Patients wil be randomized to receive tocilizumab 4mg/kg iv, tocilizumab 8mg/mg iv, or placebo iv, every 4 weeks; all patients will also receive methotrexate 10-25mg weekly. 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 a stable dose of MTX;
* 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;
* prior treatment failure 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 ACR 50/70 responses; change from baseline in ACR core set components.
timeFrame: Week 24
measure: AEs, laboratory parameters, vital signs
timeFrame: Throughout study
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Adelaide
country: Australia
city: Douglas
country: Australia
city: Maroochydore
country: Australia
city: Shenton Park
country: Australia
city: Wien
country: Austria
city: Wien
country: Austria
city: Wien
country: Austria
city: Wien
country: Austria
city: Porto Alegre
country: Brazil
city: Sao Paulo
country: Brazil
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Calgary
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Victoria
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: St John's
country: Canada
state: Newfoundland and Labrador
city: Burlington
country: Canada
state: Ontario
city: Newmarket
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Sainte-foy
country: Canada
state: Quebec
city: Hong Kong
country: China
city: Hong Kong
country: China
city: Besancon
country: France
city: Creteil
country: France
city: Le Mans
country: France
city: Montpellier
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Bad Bramstedt
country: Germany
city: Bad Nauheim
country: Germany
city: Baden-baden
country: Germany
city: Berlin
country: Germany
city: Erlangen
country: Germany
city: Heidelberg
country: Germany
city: Köln
country: Germany
city: Tübingen
country: Germany
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Pécs
country: Hungary
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Petach Tikva
country: Israel
city: Tel Aviv
country: Israel
city: Ferrara
country: Italy
city: Gazzi
country: Italy
city: Palermo
country: Italy
city: Siena
country: Italy
city: Udine
country: Italy
city: Chihuahua
country: Mexico
city: Guadalajara
country: Mexico
city: Guadalajara
country: Mexico
city: Mexico City
country: Mexico
city: Mexico City
country: Mexico
city: San Luis Potosi
country: Mexico
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Piestany
country: Slovakia
city: Bern
country: Switzerland
city: Lausanne
country: Switzerland
city: St Gallen
country: Switzerland
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: 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: Garnero P, Thompson E, Woodworth T, Smolen JS. Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone. Arthritis Rheum. 2010 Jan;62(1):33-43. doi: 10.1002/art.25053.
citation: Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Alten R; OPTION Investigators. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008 Mar 22;371(9617):987-97. doi: 10.1016/S0140-6736(08)60453-5.