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

Roche

Status and phase: Terminated; Phase 4

Conditions: Rheumatoid Arthritis

Treatments: Drug: Methotrexate (tapering dose); Drug: Tocilizumab; Drug: Methotrexate (stable dose)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01661140

2011-005260-20 (EudraCT Number)

ML28096

Details and patient eligibility

About

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.

Enrollment: 427 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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427 participants in 2 patient groups

Methotrexate (MTX) Tapering Dosage

Experimental group

Description:

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.

Treatment:

Drug: Methotrexate (tapering dose)

Drug: Tocilizumab

Methotrexate (MTX) Maintenance Dosage

Active Comparator group

Description:

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.

Treatment:

Drug: Tocilizumab

Drug: Methotrexate (stable dose)