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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00106522




Registration number
NCT00106522
Ethics application status
Date submitted
25/03/2005
Date registered
28/03/2005
Date last updated
2/11/2016

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 Currently on Methotrexate Therapy
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 Active Rheumatoid Arthritis and Inadequate Response to Anti-TNF Therapy
Secondary ID [1] 0 0
WA18062
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 - Methotrexate
Treatment: Drugs - Placebo
Treatment: Drugs - tocilizumab [RoActemra/Actemra]
Treatment: Drugs - tocilizumab [RoActemra/Actemra]

Experimental: 1 -

Experimental: 2 -

Placebo comparator: 3 -


Treatment: Drugs: Methotrexate
10-25mg weekly

Treatment: Drugs: Placebo
iv every 4 weeks

Treatment: Drugs: tocilizumab [RoActemra/Actemra]
8mg/kg iv every 4 weeks

Treatment: Drugs: tocilizumab [RoActemra/Actemra]
4mg/kg iv every 4 weeks
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
Primary outcome [2] 0 0
AEs, laboratory parameters, vital signs, ECGs.
Timepoint [2] 0 0
Throughout study
Secondary outcome [1] 0 0
Percentage of patients with ACR 50 and ACR 70 responses
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Mean changes in parameters of ACR core set
Timepoint [2] 0 0
Week 24

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 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.
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 screening, or planned major surgery within 6 months after entering study;
* 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
1/05/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2007
Sample size
Target
Accrual to date
Final
499
Recruitment in Australia
Recruitment state(s)
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- Malvern
Recruitment hospital [2] 0 0
- Shenton Park
Recruitment hospital [3] 0 0
- Sydney
Recruitment hospital [4] 0 0
- Woolloongabba
Recruitment postcode(s) [1] 0 0
3144 - Malvern
Recruitment postcode(s) [2] 0 0
6008 - Shenton Park
Recruitment postcode(s) [3] 0 0
2050 - Sydney
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment outside Australia
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Stoke-on-trent

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 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.
Trial website
https://clinicaltrials.gov/study/NCT00106522
Trial related presentations / publications
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.
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.
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.
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.
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. Erratum In: Ann Rheum Dis. 2009 Feb;68(2):296.
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/NCT00106522