A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate in Patients With Severe Active Rheumatoid Arthritis, Comparing Tapering Versus Maintaining the Methotrexate Dosage
Randomized, Phase IV, Placebo-controlled, Comparative Study to Evaluate the Efficacy and Safety of Tapering Methotrexate (MTX) Dosage Versus Maintaining the Dosage in Patients With Severe Active Rheumatoid Arthritis (RA) Who Have Demonstrated an Inadequate Response (IR) to Prior Disease-modifying Anti-rheumatic Drugs (DMARDs) Treatment and Have Initiated RoActemra (RoActemra, TCZ) in Combination With MTX
2 other identifiers
interventional
427
1 country
67
Brief Summary
This randomized, placebo-controlled, double-blind study will compare the safety and efficacy of tapering methotrexate (MTX) versus maintaining MTX dosage in patients with severe active rheumatoid arthritis and an inadequate response to disease-modifying antirheumatic drugs (DMARDs) initiated on treatment with tocilizumab. Participants will receive tocilizumab 8 mg/kg intravenously every 4 weeks and MTX orally weekly throughout the study. At Week 24, participants achieving a good/moderate EULAR response will be randomized receiving the MTX Tapering arm or MTX Maintenance arm. Up to Week 56 participants will receive either tapering or stable dose MTX in combination with tocilizumab. From Week 56 to Week 72 participants will receive tocilizumab monotherapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 rheumatoid-arthritis
Started Sep 2012
67 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 7, 2012
CompletedFirst Posted
Study publicly available on registry
August 9, 2012
CompletedStudy Start
First participant enrolled
September 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2015
CompletedResults Posted
Study results publicly available
October 14, 2016
CompletedOctober 14, 2016
August 1, 2016
2.4 years
August 7, 2012
April 26, 2016
August 19, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
Percentage of Participants Maintaining Previous Disease Activity (European League Against Rheumatism [EULAR] Response) From Week 24 (Time of Randomization) to Week 60
Response was determined using EULAR criteria based upon (Disease Activity Score In 28 Joints) DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit. Participants with a score lesser than or equal to (\<=) 3.2 and reduction of greater than (\>) 1.2 points were assessed as having a 'good' response. Participants with a score \>3.2 with reduction of \>1.2 points, or a score \<=5.1 with reduction of \>0.6 to \<=1.2 points, were assessed as having a 'moderate' response. Participants with a score \>5.1 with reduction of \>0.6 to \<=1.2 points, or any score with reduction \<=0.6 points, were assessed as non-responders with response recorded as 'none.'
From randomization to Week 60
Secondary Outcomes (17)
Change From Baseline in Disease Activity Score In 28 Joints (DAS28) Score at Week 60
Randomization (Week 24), Week 60
Change From Baseline in Disease Activity Score In 28 Joints (DAS28) Score at Week 72
Randomization (Week 24), Week 72
Percentage of Participants Who Achieve Score of <=1 in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 60 and 72
Week 60, 72
Percentage of Participants Who Achieve a Disease Activity Score In 28 Joints (DAS28) <= 3.2
Week 60, 72
Percentage of Participants Who Achieve DAS28 Remission (DAS28 < 2.6)
Week 60, 72
- +12 more secondary outcomes
Study Arms (2)
Methotrexate (MTX) Tapering Dosage
EXPERIMENTALAt Week 0 participants will start open-label tocilizumab and open-label MTX for 24 weeks. At Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response will be randomized to the MTX Tapering group or MTX Maintenance group. In this arm participants will receive a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. Participants will also continue to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants will receive tocilizumab monotherapy.
Methotrexate (MTX) Maintenance Dosage
ACTIVE COMPARATORAt Week 0 participants will start open-label tocilizumab and open-label MTX for 24 weeks. At Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response will be randomized to the MTX Tapering group or MTX Maintenance group. In this arm participants will continue to be administered a stable dose of MTX in a double-blind fashion between Week 24 and Week 56. Participants will also continue to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants will receive tocilizumab monotherapy.
Interventions
Methotrexate (MTX) was administered weekly according to the subject's pre-study MTX dose
8 mg/kg intravenously every 4 weeks for 72 weeks
Tapering doses of methotrexate (MTX) were administered weekly from Week 24 to Week 56. Tapering doses depended on dose administered to the subject during the open label period. First tapering occurred at randomization (Week 24), second tapering at Week 32, third tapering at Week 40 and final tapering at Week 48.
Eligibility Criteria
You may qualify if:
- Adult patients, \>/= 18 years of age
- Active severe rheumatoid arthritis (DAS28 \> 5.1) according to European League of Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria
- Inadequate response to a trial of 2 DMARDs, including methotrexate, a trial being defined as 6 months with 2 months at standard dose; no previous treatment with a biologic agent such as a tumor necrosis factor (TNF) inhibitor
- Oral corticosteroids must have been at a stable dose of \</= 10 mg/day prednisolone or equivalent for at least 25 out of 28 days prior to start of treatment (Day 1)
You may not qualify if:
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization
- Rheumatic autoimmune disease other than rheumatoid arthritis
- Functional class IV as defined by the ACR Classification of Functional Status in RA
- Prior history of or current inflammatory joint disease other than RA
- Previous treatment with tocilizumab
- Previous treatment with any biologic drug (e.g. TNF inhibitor) that is used in the treatment of RA
- Intraarticular or parenteral corticosteroids within 6 weeks prior to enrollment
- Inadequate liver, bone marrow or hepatic function
- Positive for hepatitis B, hepatitis C or HIV infection
- Pregnant or breastfeeding women
- Females of child-bearing potential who are not using reliable means of contraception
- History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
- Active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections
- History of, or currently active, primary or secondary immunodeficiency
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (67)
Unknown Facility
Aberdeen, AB25 2ZN, United Kingdom
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Abergavenny, NP7 7EG, United Kingdom
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Ashford, TW15 3AA, United Kingdom
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Aylesbury, HP21 8AL, United Kingdom
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Barnsley, S75 2EP, United Kingdom
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Basingstoke, RG24 9NA, United Kingdom
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Bournemouth, BH23 2JX, United Kingdom
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Brighton, BN2 5BE, United Kingdom
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Bury Saint Edmonds, IP33 2QZ, United Kingdom
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Cambridge, CB2 2QQ, United Kingdom
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Cannock, WS11 5XY, United Kingdom
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Cardiff, CF14 4XW, United Kingdom
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Chelmsford, CM1 7ET, United Kingdom
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Chester, CH2 1UL, United Kingdom
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Coventry, CV2 2DX, United Kingdom
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Crewe, CW1 4QJ, United Kingdom
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Darlington, DL3 6HX, United Kingdom
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Derby, DE22 3NE, United Kingdom
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Dudley, DY1 2HQ, United Kingdom
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Dundee, DD12 9SY, United Kingdom
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Eastbourne, BN21 2UD, United Kingdom
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Exeter, EX2 5DW, United Kingdom
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Gillingham, ME7 5NY, United Kingdom
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Greenock, PA16 0XN, United Kingdom
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Guildford, GU2 7XX, United Kingdom
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Harrogate, HG2 7SX, United Kingdom
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Hull, HU3 3JZ, United Kingdom
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Isle of Wight, PO30 5TG, United Kingdom
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Leeds, LS7 4SA, United Kingdom
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Liverpool, L9 7AL, United Kingdom
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Llantrisant, CF72 8XR, United Kingdom
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London, E11 1NR, United Kingdom
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London, SE18 4QH, United Kingdom
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London, SW17 0QT, United Kingdom
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London, W6 8RF, United Kingdom
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Londonderry, BT47 6SB, United Kingdom
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Maidstone, ME16 9QQ, United Kingdom
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Manchester, M13 9PT, United Kingdom
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Manchester, M41 5SL, United Kingdom
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Metropolitan Borough of Wirral, CH49 5PE, United Kingdom
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Middlesbrough, TS4 3BW, United Kingdom
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North Shields, NE29 8NH, United Kingdom
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Northampton, NN1 5BD, United Kingdom
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Nottingham, NG7 2UH, United Kingdom
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Oldham, OL1 1NL, United Kingdom
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Plymouth, PL6 8DH, United Kingdom
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Reading, RG1 5AN, United Kingdom
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Salford, M6 8HD, United Kingdom
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Salisbury, SP2 8BJ, United Kingdom
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Sheffield, S10 2JF, United Kingdom
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Somerset, TA1 5DA, United Kingdom
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Southampton, SO16 6YD, United Kingdom
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Southport, PR8 6PN, United Kingdom
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Stevenage, SG1 4AB, United Kingdom
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Stoke-on-Trent, ST6 7AG, United Kingdom
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Sunderland, SR4 7TP, United Kingdom
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Sutton in Ashfield, NG17 4JL, United Kingdom
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Swindon, SN3 6BB, United Kingdom
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Torquay, TQ2 7AA, United Kingdom
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Truro, TR1 3LJ, United Kingdom
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Walsall, WS2 9PS, United Kingdom
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Warwick, CV34 5BW, United Kingdom
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Westcliffe-on-sea, SS0 0RY, United Kingdom
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Wolverhampton, WV10 0QP, United Kingdom
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Worthing, BN11 2DH, United Kingdom
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Wrightington, WN6 9EP, United Kingdom
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York, YO31 8HE, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 7, 2012
First Posted
August 9, 2012
Study Start
September 1, 2012
Primary Completion
February 1, 2015
Study Completion
February 1, 2015
Last Updated
October 14, 2016
Results First Posted
October 14, 2016
Record last verified: 2016-08