A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate in Patients With Severe Active Rheumatoid Arthritis, Comparing Tapering Versus Maintaining the Methotrexate Dosage

NCT ID: NCT01661140

Last Updated: 2016-10-14

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

427 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-09-30

Study Completion Date

2015-02-28

Brief Summary

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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.

Detailed Description

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Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Methotrexate (MTX) Tapering Dosage

At 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.

Group Type EXPERIMENTAL

Tocilizumab

Intervention Type DRUG

8 mg/kg intravenously every 4 weeks for 72 weeks

Methotrexate (tapering dose)

Intervention Type DRUG

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.

Methotrexate (MTX) Maintenance Dosage

At 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.

Group Type ACTIVE_COMPARATOR

Methotrexate (stable dose)

Intervention Type DRUG

Methotrexate (MTX) was administered weekly according to the subject's pre-study MTX dose

Tocilizumab

Intervention Type DRUG

8 mg/kg intravenously every 4 weeks for 72 weeks

Interventions

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Methotrexate (stable dose)

Methotrexate (MTX) was administered weekly according to the subject's pre-study MTX dose

Intervention Type DRUG

Tocilizumab

8 mg/kg intravenously every 4 weeks for 72 weeks

Intervention Type DRUG

Methotrexate (tapering dose)

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.

Intervention Type DRUG

Other Intervention Names

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RoActemra/Actemra

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Aberdeen, , United Kingdom

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Abergavenny, , United Kingdom

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Ashford, , United Kingdom

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Aylesbury, , United Kingdom

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Barnsley, , United Kingdom

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Basingstoke, , United Kingdom

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Bournemouth, , United Kingdom

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Brighton, , United Kingdom

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Bury Saint Edmonds, , United Kingdom

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Cambridge, , United Kingdom

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Cannock, , United Kingdom

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Cardiff, , United Kingdom

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Chelmsford, , United Kingdom

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Chester, , United Kingdom

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Coventry, , United Kingdom

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Crewe, , United Kingdom

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Darlington, , United Kingdom

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Derby, , United Kingdom

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Dudley, , United Kingdom

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Dundee, , United Kingdom

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Eastbourne, , United Kingdom

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Exeter, , United Kingdom

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Gillingham, , United Kingdom

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Greenock, , United Kingdom

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Guildford, , United Kingdom

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Harrogate, , United Kingdom

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Hull, , United Kingdom

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Isle of Wight, , United Kingdom

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Leeds, , United Kingdom

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Liverpool, , United Kingdom

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Llantrisant, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Londonderry, , United Kingdom

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Maidstone, , United Kingdom

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Manchester, , United Kingdom

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Manchester, , United Kingdom

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Metropolitan Borough of Wirral, , United Kingdom

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Middlesbrough, , United Kingdom

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North Shields, , United Kingdom

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Northampton, , United Kingdom

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Nottingham, , United Kingdom

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Oldham, , United Kingdom

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Plymouth, , United Kingdom

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Reading, , United Kingdom

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Salford, , United Kingdom

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Salisbury, , United Kingdom

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Sheffield, , United Kingdom

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Somerset, , United Kingdom

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Southampton, , United Kingdom

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Southport, , United Kingdom

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Stevenage, , United Kingdom

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Stoke-on-Trent, , United Kingdom

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Sunderland, , United Kingdom

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Sutton in Ashfield, , United Kingdom

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Swindon, , United Kingdom

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Torquay, , United Kingdom

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Truro, , United Kingdom

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Walsall, , United Kingdom

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Warwick, , United Kingdom

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Westcliffe-on-sea, , United Kingdom

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Wolverhampton, , United Kingdom

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Worthing, , United Kingdom

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Wrightington, , United Kingdom

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York, , United Kingdom

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Countries

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United Kingdom

Other Identifiers

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2011-005260-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ML28096

Identifier Type: -

Identifier Source: org_study_id

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