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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00106548




Registration number
NCT00106548
Ethics application status
Date submitted
25/03/2005
Date registered
28/03/2005
Date last updated
11/06/2010

Titles & IDs
Public title
A Study to Assess the Effect of Tocilizumab + Methotrexate on Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis
Scientific 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
Secondary ID [1] 0 0
WA17822
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - tocilizumab [RoActemra/Actemra]
Treatment: Drugs - tocilizumab [RoActemra/Actemra]
Treatment: Drugs - Placebo
Treatment: Drugs - Methotrexate

Experimental: 1 -

Experimental: 2 -

Placebo comparator: 3 -


Treatment: Drugs: tocilizumab [RoActemra/Actemra]
4mg/kg iv / month

Treatment: Drugs: tocilizumab [RoActemra/Actemra]
8mg/kg iv / month

Treatment: Drugs: Placebo
iv / month

Treatment: Drugs: Methotrexate
10-25mg/week
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of patients with ACR 20 response
Timepoint [1] 0 0
Week 24
Secondary outcome [1] 0 0
Percentage of patients ACR 50/70 responses; change from baseline in ACR core set components.
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
AEs, laboratory parameters, vital signs
Timepoint [2] 0 0
Throughout study

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2007
Sample size
Target
Accrual to date
Final
623
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Douglas
Recruitment hospital [3] 0 0
- Maroochydore
Recruitment hospital [4] 0 0
- Shenton Park
Recruitment postcode(s) [1] 0 0
5041 - Adelaide
Recruitment postcode(s) [2] 0 0
4184 - Douglas
Recruitment postcode(s) [3] 0 0
4558 - Maroochydore
Recruitment postcode(s) [4] 0 0
6008 - Shenton Park
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Austria
State/province [2] 0 0
Wien
Country [3] 0 0
Brazil
State/province [3] 0 0
Porto Alegre
Country [4] 0 0
Brazil
State/province [4] 0 0
Sao Paulo
Country [5] 0 0
Bulgaria
State/province [5] 0 0
Sofia
Country [6] 0 0
Bulgaria
State/province [6] 0 0
Varna
Country [7] 0 0
Canada
State/province [7] 0 0
Alberta
Country [8] 0 0
Canada
State/province [8] 0 0
British Columbia
Country [9] 0 0
Canada
State/province [9] 0 0
Manitoba
Country [10] 0 0
Canada
State/province [10] 0 0
Newfoundland and Labrador
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
China
State/province [13] 0 0
Hong Kong
Country [14] 0 0
France
State/province [14] 0 0
Besancon
Country [15] 0 0
France
State/province [15] 0 0
Creteil
Country [16] 0 0
France
State/province [16] 0 0
Le Mans
Country [17] 0 0
France
State/province [17] 0 0
Montpellier
Country [18] 0 0
France
State/province [18] 0 0
Paris
Country [19] 0 0
Germany
State/province [19] 0 0
Bad Bramstedt
Country [20] 0 0
Germany
State/province [20] 0 0
Bad Nauheim
Country [21] 0 0
Germany
State/province [21] 0 0
Baden-baden
Country [22] 0 0
Germany
State/province [22] 0 0
Berlin
Country [23] 0 0
Germany
State/province [23] 0 0
Erlangen
Country [24] 0 0
Germany
State/province [24] 0 0
Heidelberg
Country [25] 0 0
Germany
State/province [25] 0 0
Köln
Country [26] 0 0
Germany
State/province [26] 0 0
Tübingen
Country [27] 0 0
Hungary
State/province [27] 0 0
Budapest
Country [28] 0 0
Hungary
State/province [28] 0 0
Debrecen
Country [29] 0 0
Hungary
State/province [29] 0 0
Pécs
Country [30] 0 0
Israel
State/province [30] 0 0
Beer Sheva
Country [31] 0 0
Israel
State/province [31] 0 0
Haifa
Country [32] 0 0
Israel
State/province [32] 0 0
Jerusalem
Country [33] 0 0
Israel
State/province [33] 0 0
Petach Tikva
Country [34] 0 0
Israel
State/province [34] 0 0
Tel Aviv
Country [35] 0 0
Italy
State/province [35] 0 0
Ferrara
Country [36] 0 0
Italy
State/province [36] 0 0
Gazzi
Country [37] 0 0
Italy
State/province [37] 0 0
Palermo
Country [38] 0 0
Italy
State/province [38] 0 0
Siena
Country [39] 0 0
Italy
State/province [39] 0 0
Udine
Country [40] 0 0
Mexico
State/province [40] 0 0
Chihuahua
Country [41] 0 0
Mexico
State/province [41] 0 0
Guadalajara
Country [42] 0 0
Mexico
State/province [42] 0 0
Mexico City
Country [43] 0 0
Mexico
State/province [43] 0 0
San Luis Potosi
Country [44] 0 0
Singapore
State/province [44] 0 0
Singapore
Country [45] 0 0
Slovakia
State/province [45] 0 0
Piestany
Country [46] 0 0
Switzerland
State/province [46] 0 0
Bern
Country [47] 0 0
Switzerland
State/province [47] 0 0
Lausanne
Country [48] 0 0
Switzerland
State/province [48] 0 0
St Gallen
Country [49] 0 0
Thailand
State/province [49] 0 0
Bangkok
Country [50] 0 0
Thailand
State/province [50] 0 0
Chiang Mai

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00106548
Trial related presentations / publications
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00106548