A Study of Tocilizumab and Methotrexate in Combination or as Monotherapy in Treatment-Naïve Patients With Early Rheumatoid Arthritis

Roche

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: methotrexate; Drug: placebo MTX; Drug: tocilizumab [RoActemra/Actemra]; Drug: placebo TCZ

Study type: Interventional

Funder types: Industry

Identifiers

NCT01034137

ML22497

2009-013316-12

Details and patient eligibility

About

This randomized, double-blind, placebo-controlled study will compare the efficacy with regard to sustained remission and safety of tocilizumab and methotrexate, in combination or as monotherapy, in treatment-naïve patients with early rheumatoid arthritis. Patients will be randomized to receive either tocilizumab (8mg/kg iv every 4 weeks) plus weekly methotrexate (po in ascending doses), or tocilizumab (8mg/kg iv every 4 weeks) plus placebo, or methotrexate plus placebo. Anticipated time on study treatment is 2 years, and target sample size is 300.

Full description

Multi-center, randomized, double-blind, placebo-controlled (double placebo) three-arm parallel group, comparative study. Patients were randomized in a 1:1:1 ratio to one of the following treatments:

TCZ 8 milligram (mg)/kilogram (kg) + MTX (Group I: TCZ+MTX) TCZ 8 mg/kg + placeboMTX (Group II: TCZ+placebo) MTX + placeboTCZ (Group III: MTX+placebo)

Randomization was stratified by participating center and baseline Disease Activity Score, scoring 28 joints (DAS28) level (<5.1 vs. ≥5.1). Patients were evaluated every 4 weeks and at each visit a decision on dosage changes was made based on efficacy parameters (DAS28) and occurrence of adverse events (AEs). Patients received MTX/placeboMTX in climbing dosages. Hydroxychloroquine (HCQ) was added when remission was not reached with the maximum tolerable dosage (MTD) of MTX/placeboMTX. If after 12 additional weeks remission was not reached, HCQ was stopped and replaced by standard of care therapy (in Group I) or placebo therapy was replaced by the corresponding verum resulting in TCZ+MTX combination therapy (in Groups II and III). In case remission was reached, MTX/placeboMTX and TCZ/placeboTCZ had to be decreased. Patients were followed for a maximum of 24 months

Enrollment: 317 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• adult patients, >/=18 years of age
• early rheumatoid arthritis (disease symptoms <1 year) according to ACR criteria
• disease activity DAS28 >2.6
• body weight </=110kg, BMI </=36

Exclusion criteria

• rheumatic autoimmune disease other than RA
• current inflammatory joint disease other than RA
• previous treatment with any DMARD or biologic drug used in the treatment of RA
• intra-articular, parenteral or oral glucocorticoids used for the arthritis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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317 participants in 3 patient groups

Tocilizumab + Methotrexate

Experimental group

Description:

Participants will receive intravenous (IV) TCZ 8 mg/kg every four weeks for a maximum of 26 infusions + oral capsules of MTX 10-30 mg/week in climbing dosages of 5 mg starting at 10 mg up till a maximum dosage of 30 mg/week. The weekly dose of MTX will be taken on one particular day of the week.

Treatment:

Drug: tocilizumab [RoActemra/Actemra]

Drug: methotrexate

Tocilizumab + Placebo Methotrexate

Active Comparator group

Description:

Participants will receive IV TCZ 8 mg/kg every four weeks for a maximum of 26 infusions + weekly oral matching placebo MTX capsules in climbing dosages. The weekly dose of placebo MTX will be taken on one particular day of the week.

Treatment:

Drug: tocilizumab [RoActemra/Actemra]

Drug: placebo MTX

Methotrexate + Placebo Tocilizumab

Active Comparator group

Description:

Participants will receive weekly oral MTX in climbing dosages of 5 mg starting at 10 mg up till a maximum dosage of 30 mg/week + matching placebo TCZ IV 8 mg/kg every four week for a maximum of 26 infusions. The weekly dose of MTX will be taken on one particular day of the week.

Treatment:

Drug: placebo TCZ

Drug: methotrexate